Category Archives: Gastrointestinal

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Bifidobacterium in the Gut Microbiota Declines in the Aging Adult: Guidance on How to Repopulate and Increase Bifidobacterium in the Gastrointestinal Tract

Human Health Depends on a Beneficial and Diverse Gut Microbiota

In order to establish and maintain the health of the host, the intestinal microbiota in general and bifidobacterium in particular are very important.

Regardless of age, studies have determined that human health depends greatly on a beneficial gut microbiota.  1  One study from 2006 called the gut microbiota as the “forgotten organ.”  2 

The aging process can alter and affect the composition and functions of bacterial species in the gut microbiota.   A major consequence of the aging process, coupled with poor eating habits, extended use of antibiotics and stress is a loss of diversity in the gut microbiota.  In general a high diversity of gut organisms has been associated with states of relatively good health, while low diversity has been associated with states of disease or chronic dysfunction.  3 4

At the later stages of life the microbiota composition becomes less diverse, with a higher Bacteroides to Firmicutes ratio, an increase in Proteobacteria and decrease in Bifidobacterium.  5 

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Human microbiota: onset and shaping through life stages and perturbations. The graph provides a global overview of the relative abundance of key phyla of the human microbiota composition in different stages of life. Measured by either 16S RNA or metagenomic approaches (DNA). Data arriving from: Babies breast- and formula-fed (Schwartz et al., 2012), baby solid food (Koenig et al., 2011), toddler antibiotic treatment (Koenig et al., 2011), toddler healthy or malnourished (Monira et al., 2011), adult, elderly, and centenarian healthy (Biagi et al., 2010), and adult obese (Zhang et al., 2009).  Source:  The function of our microbiota: who is out there and what do they do?

The microbiota acclimates changes during the aging process as illustrated in the diagram below:

Development of human gut microbiota from prenatal to elderly. It is believed that infants are born with a sterile gastrointestinal track. During birth, the infant gut is exposed to microbes from the mother’s reproductive tract and environment and the gut microbiota starts colonizing. Up to the first two years of life, the composition of the gut microbiota often varies. After two years, when children are started to eat solid food (e.g. fibers and complex carbohydrates), the gut microbiota becomes more diverse and stable. In old age, the gut microbiota alters drastically and shows less diversity compared to younger age.

Development of human gut microbiota from prenatal to elderly. It is believed that infants are born with a sterile gastrointestinal track. During birth, the infant gut is exposed to microbes from the mother’s reproductive tract and environment and the gut microbiota starts colonizing. Up to the first two years of life, the composition of the gut microbiota often varies. After two years, when children are started to eat solid food (e.g. fibers and complex carbohydrates), the gut microbiota becomes more diverse and stable. In old age, the gut microbiota alters drastically and shows less diversity compared to younger age.  Source: Human gut microbiota and healthy aging: Recent developments and future prospective

Diversity Association is a proxy measure of gut biodiversity, which is defined as the number and abundance of distinct types of organisms present in the gut.  6  

The Diversity Association (DA) graphic is a global biomarker of overall gut health status and serves as a proxy measure of gut biodiversity. Specifically, the Diversity Association graphic represents the results of a proprietary algorithm based on selected commensal targets that appear to correlate with gut health status.

Diversity Association is graphically represented on a vertical ascending scale reflecting lower to higher overall diversity. In the gut, higher diversity is associated with gut health.

  • A Diversity Association indicator in the lower half of the graphical bar indicates a high likelihood that a patient’s gut is not healthy
  • A Diversity Association in the upper quartile of the graphical bar indicates high likelihood that a patient’s gut is healthy

The clinical utility of the Diversity Association is based on a growing body of research demonstrating that lower gut diversity is associated with clinical disease. As such, therapeutic interventions to restore gut balance (including dietary manipulation, prebiotics and/or probiotics, as well as other clinical strategies to heal the gut) are consistent with emerging clinical science on biodiversity.   7

 

Example of Diversity Association from Genova Diagnostics:

GI Effects® Comprehensive Profile – Stool

The prevalence of intestinal dysbiosis is the loss of microbiota diversity (LOMD).  8   This loss of microbiota diversity is in part due to the modern Western lifestyle.  9 

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Associative links between Western lifestyle, Human conditions, and loss of microbial diversity (LOMD). On one hand, most of the Human diseases affecting westernized countries are associated with LOMD and on the other hand, some western lifestyle patterns cause LOMD. Then, LOMD appears to play a central role linking western lifestyle and western chronic human conditions.  *LOMD not assessed.  Source:  Gut Microbiota Diversity and Human Diseases: Should We Reintroduce Key Predators in Our Ecosystem?

Bifidobacterium is Critical to a Healthy Gut Microbiota

The most frequently observed intestinal microbiota alteration is the aberrant number or composition of bifidobacteria in the gut microbiota.  The population of bifidobacteria plays a very important role in intestinal homeostasis. 10

The NCBI data base, as of April 2016, holds 254 publicly available bifidobacterial genome sequences, of which sixty one represent complete genome sequences.  11  The Table below lists all the completely sequenced bifidobacterial genomes:  12

Table 1. Summary of all completely sequenced bifidobacterial genomes

A study from 2014 identified the most abundant bifidobacterial species present in the human gut, being represented by:  13

  • B. longum
  • B. pseudolongum
  • B. animalis subsp. lactis
  • B. adolescentis
  • B. bifidum
  • B. pseudocatenulatum
  • B. breve

Studies agree that the most abundant species of bifidobacteria is B. longum.  14  In adults, some studies have identified higher levels of B. adolescentis and B. catenulatum15  

The intestines of healthy breast fed infants are dominated by bifidobacterium. During the first three years of life, the fecal microbiota then gradually develops into the microbiota of adults. 

The strains commonly dominant in infants include:  16  17

  • B. longum
  • B. breve
  • B. bifidum subsp. infantis

However, by adulthood, bifidobacteria is lower but relatively stable and account for 10-20% of intestinal bacteria. 18  The presence of different species of bifidobacteria changes with age, from childhood to old age.

The strains commonly dominant in adults include:

  • B. catenulatum
  • B. adolescentis
  • B. longum

The intestinal flora then begins to again show changes during the transition from middle age to old age.  In old age (starting roughly at age 55), bifidobacterium decrease considerably.  19  20  The reported decline in bifidobacteria population with aging was accompanied by a decrease in species diversity.

FIGURE 1. At birth levels of bifidobacteria are found to be at their highest. In cases of natural childbirth the numbers are highest at birth. In contrast, they are lower in C sectioned babies. Various diseases such as obesity, diabetes and allergies have been associated with lower numbers of bifidobacteria at various stages of life. When weaned onto solid foods diet is more of an intervening factor and an adult-like (stable) microbiota develops. In this figure the authors hypothesize with regard to the relative abundance of bifidobacteria present at each stage of the life cycle, based on the literature cited in the following review by Voreades et al. (2014).  Source:  Gut Bifidobacteria Populations in Human Health and Aging

Certain research demonstrates that the decline in bifidobacteria in old age is associated with the reduction in adhesion to the intestinal mucosa.  21  However, an extrinsic factor, which is the extended use of antibiotics, may indirectly affect the bifidobacteria composition drastically. 22 

The Table below shows the distribution of the most abundant bifidobacterium species in the intestinal microbiota at different stages of life analyzed using different techniques:

Source: Gut Bifidobacteria Populations in Human Health and Aging

The three diagrams/figures below illustrate the fact that the intestinal flora begins to change during the transition from middle age to old age, with a reduction in the bifidobacterium. This reduction in the bifidobacterium has been claimed to be from the effect that aging of physiologic function in the host has on the intestinal bacterial microbiota; and due to this result can further accelerate the aging process.  23

Intestinal Flora and Age

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Changes in the fecal microbiota with increasing age.  Source:  Establishment of Intestinal Bacteriology

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Evolution of some representatives of the intestinal microbiota accordingly to age  Source:  Intestinal microbiota in health and disease: Role of bifidobacteria in gut homeostasis

Researchers have identified differences in the predominant bifidobacterium species or biotypes in different age groups of humans.  24

The Table below shows the frequency of occurrence of species and biotypes of bifidobacteria in feces of various age groups of humans:

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Source:  Establishment of Intestinal Bacteriology

Reduction in Bifidobacterium and Its Link to Various Diseases

Alterations in number and composition of the populations of bifidobacteria is one of the most frequent features present in various diseases.  This loss and reduction of bifidobacteria is called bifidobacterial dysbiosis.

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Bifidobacterial dysbiosis and its relationship with diseases: A target for probiotic intervention. IBD: Inflammatory bowel disease; IBS: Irritable bowel syndrome.   Source:  Intestinal microbiota in health and disease: Role of bifidobacteria in gut homeostasis

Bifidobacteria dysbiosis has been shown to lead to or be a cause of the following disease states:

  • allergy 25
  • atherosclerosis 26  27
  • atopic disease  28  29 
  • autism 30
  • celiac disease  31  32
  • colorectal cancer  33
  • diabetes – type 1 and type 2 34  35  36
  • inflammatory bowel disease 37  38  39
  • intestinal inflammation 40
  • irritable bowel syndrome 41  42  43  44
  • obesity 45  46

The Multiple Benefits of Bifidobacterium

Bifidobacterium has been studied extensively for its multiple benefits on human physiology.  Among the many benefits of bifidobacterium, the important ones include:

  • Bifidobacteria produces a number of potentially health promoting metabolites including:
    • short chain fatty acid acetic acid  47
    • conjugated linoleic acid  48 
    • bacteriocins  (Bacteriocins are an abundant and diverse group of ribosomally synthesized antimicrobial peptides)  49  
  • Bifidobacteria produce lactic acid (lactate) 50  51
  • Bifidobacteria detoxifies toxic substances
    • Bifidobacteria may lower blood ammonia levels  52
    • Bifidobacteria may reduce levels of beta-glucuronidase (activates various carcinogens and mutagens)  53 
    • Bifidobacteria may facilitate the detoxification and excretion of mercury 54
  • Bifidobacteria produce and synthesize B vitamins 55  56
  • Bifidobacteria do not produce the short-chain fatty acid butyrate directly, they do produce lactate that may be transformed in butyrate  57
  • Abundance  of bifidobacterium is associated with higher bacterial gene richness in the gut  58

Repopulating and Increasing Bifidobacterium in the Gastrointestinal Tract

As has been established, the colonic microbiota undergoes certain age related changes that may affect health. Above the age of 55-65 years, populations of bifidobacteria are known to decrease markedly.  59  It is important for persons at or above this age range to be proactive in replacing the lost bifidobacterium and to increase the population of bifidobacterium in the gastrointestinal tract. 

There are three ways in which to increase the population of bifidobacterium in the gastrointestinal tract.  These include:

  • Bifidogenic Factor
  • Bifidobacterium in food
  • Bifidobacterium in supplements (probiotics)

Bifidogenic Factor

A bifidogenic factor, also known as bifidus factor, is a compound that specifically enhances the growth of bifidobacteria in the gastrointestinal tract.  Most of the products available as bifidogenic factors consist of fibers and are known as prebiotics.  Fibrous substrates act as prebiotics for developing a beneficial gut microbiota.

It has been determined that elderly people consume low amounts of fibers which causes a negative impact on gut microbiota diversity.  60   

The following fibers are known to act as bifidogenic factors thus stimulating the growth of bifidobacteria:

  • Amylose  61
  • Apple Pectin  62
  • Fructo-oligosaccharides  63
  • Galactooligosaccharides  64
  • Gum Arabic  65
  • Inulin  66
  • Isomalto-oligosaccharide  67
  • Lactulose  68
  • Larch Arabinogalactan  69
  • Mannooligosaccharides 70
  • Resistant starch 71
  • Transgalactosylatedoligosaccharides  72
  • Xylooligosaccharides  73

In a study from 2010, done with human subjects, resistant starch showed significant growth of bifidobacteria in the gastrointestinal tract.  74  Resistant starch is starch and starch degradation products that avoid digestion in the small intestine and are fermented in the large intestine by beneficial bacteria.  Resistant starch occurs naturally in various foods.  The Table below list those foods in which resistant starch naturally occurs:

Examples of naturally occurring resistant starch*
Food Serving size Resistant starch
(grams)
Banana flour, from green bananas 1/4 cup, uncooked 10.5-13.2
Banana, raw, slightly green 1 medium, peeled 4.7
High amylose RS2 corn resistant starch 1 tablespoon (9.5 g) 4.5
Oats, rolled 1/4 cup, uncooked 4.4
Green peas, frozen 1 cup, cooked 4.0
White beans 1/2 cup, cooked 3.7
Lentils 1/2 cup cooked 2.5
Cold pasta 1 cup 1.9
Pearl barley 1/2 cup cooked 1.6
Cold potato 1/2″ diameter 0.6 – 0.8
Oatmeal 1 cup cooked 0.5

Source:  Wikipedia – Resistant Starch

Another bifidogenic factor, other than a specific fiber, is actually a beneficial bacteria found in the human gastrointestinal tract, called propionibacterium freudenreichii.  Propionibacterium freudenreichii produces a Bifidogenic Growth Stimulator (BGS) named ACNQ which selectively enhances the utilization of oligosaccharides by bifidobacteria.  75

Bifidobacterium in Food

Foods rich in bifidobacteria are not widespread and mostly include fermented dairy products.  The most common fermented dairy products that contain bifidobacteria include:

  • Yogurt (Cow and goat milk)
  • Kefir (Cow and goat milk)
  • Lassi (yogurt drink from the Indian subcontinent)

The Table below lists the various bifidobacterium strains found in each of the three fermented dairy products:

Bacteria

Yogurt

Kefir

Lassi

B. bifidus

X

X

 

B. animalis

X

 

 

B. animalis BB-12

 

X

 

B. lactis

 

X

X

B. lactis BB-12

X

 

 

B. breve

 

X

X

B. longum

 

X

X

B. regularis

X

 

 

Propionibacterium freudenreichii

 

 

X

Note:  Not all the commercially available products may contain all the listed bifidobacteria strains

Bifidobacterium in Supplements (Probiotics)

Other than the three fermented dairy products, no other foods contain bifidobacterium in any great quantities.  It therefore may be necessary to supplement with a combination of bifidobacterial strains in the form of a probiotic supplement in order to increase the gastrointestinal tract with bifidobacterium.

Consuming probiotic supplements that contain bifidobacteria can be very beneficial and efficient in obtaining proper quantities of bifidobacteria.  There are probiotic products that specifically contain only bifidobacteria strains and others that contain mixtures of bifidobacteria strains and lactobacillus strains.

Some of the more common strains of bifidobacterium species and strains found in probiotic products include:

  • B. adolescentis
  • B. animalis
  • B. bifidum
  • B. breve
  • B. infantis
  • B. lactis
  • B. lactis DN-173 010
  • B. lactis DR10
  • B. lactis HN019
  • B. longum
  • Bifantis
  • Bifidus DR10
  • Bifidus Regularis
  • HOWARU Bifido

Colon's friendly bifidobacteria population decreases from the age of 50

Bifidobacteria Levels Decline With Age How To Replace Bifidobacteria

Cover image credits from www.sott.net

The Multiple Health Benefits of Tributyrin, a Triglyceride Form of Butyrate

Short-Chain Fatty Acids

A considerable amount of scientific interest has been focused on short chain fatty acids (SCFAs) for improving colonic and systemic health, and specifically reducing the risk of inflammatory diseases, diabetes, and cardiovascular disease.

Researchers have shown that SCFAs have distinct physiological effects:  1

  • they contribute to shaping the gut environment
  • they influence the physiology of the colon
  • they can be used as energy sources by host cells and the intestinal microbiota 
  • they also participate in different host-signaling mechanisms

Prebiotics, which consist of primarily dietary carbohydrates such as resistant starch and dietary fibers, are the substrates in the large intestine for fermentation that produce SCFAs.  The other source of SCFA, although in smaller amounts than dietary carbohydrates, are amino acids.  Three amino acids:

  • valine
  • leucine
  • isoleucine

obtained from protein breakdown can be converted into isobutyrate, isovalerate, and 2-methyl butyrate, known as branched-chain SCFAs (BSCFAs), which contribute very little (5%) to total SCFA production.  2

There are seven short-chain fatty acids that are produced by the large intestine through the fermentation of dietary fiber and resistant starch.  Of these seven short-chain fatty acids, three of them are the most important and common:

  • acetate
  • propionate
  • butyrate

These three represent about 90–95% of the SCFA present in the colon.  The rate and amount of SCFA production depends on the species and amounts of microflora present in the colon, the substrate source and gut transit time.

Butyrate is the major energy source for colonocytes. Propionate is largely taken up by the liver. Acetate enters the peripheral circulation to be metabolized by peripheral tissues and is the principal SCFA in the colon, and after absorption it has been shown to increase cholesterol synthesis.

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Figure 1.  Fibers, specific oligosaccharides and resistant starch reach the colon intact, where they induce shifts in the composition and function of intestinal bacteria (shifts indicated by different colors). Intestinal bacteria use these compounds as substrates for the production of the short-chain fatty acids acetate, propionate and butyrate. These microbial metabolites are taken up by intestinal epithelial cells called enterocytes. Butyrate mainly feeds the enterocytes, whereas acetate and propionate reach the liver by the portal vein.  (Source:  You are what you eat,  Nature Biotechnology  32, 243–245 (2014) doi:10.1038/nbt.2845)

Butyrate (Butyric Acid)

The most important short-chain fatty acid is butyrate.

Butyrate is a primary energy source for colonic cells.  3 4   Butyrate also has demonstrated anti-inflammatory properties.  5  Butyrate may also have a role in preventing certain types of colitis. A diet low in resistant starch and fiber, which will result in a low production of SCFAs in the colon, may explain the high occurrence of colonic disorders seen in the Western civilization.  6

Studies have demonstrated that butyrate has anti-carcinogenic properties:

  • It inhibits the growth and proliferation of tumor cell lines in vitro.  7
  • It induces differentiation of tumor cells, producing a phenotype similar to that of the normal mature cell.  8
  • It induces apoptosis or programmed cell death of human colorectal cancer cells.  9 10
  • It inhibits angiogenesis by inactivating Sp1 transcription factor activity and down regulating VEGF gene expression. 11

Butyrate has been studied for its role in nourishing the colonic mucosa and in the prevention of cancer of the colon, by promoting cell differentiation, cell-cycle arrest and apoptosis of transformed colonocytes; inhibiting the enzyme histone deacetylase and decreasing the transformation of primary to secondary bile acids as a result of colonic acidification.

Therefore, a greater increase in SCFA production and potentially a greater delivery of SCFA, specifically butyrate, to the distal colon may result in a protective effect.   12

Butyrate is mainly taken up by the colon epithelial cells, only small amounts reach the portal vein and the systemic circulation.  The primary beneficial effects of butyrate occurs at the intestinal level, yet there are additional benefits at the extra intestinal level:

Intestinal effects

  • Is the preferred energy source for the colon epithelial cells
  • Decreases the pH of the colon (which decreases bile salt solubility, increases mineral absorption, decreases ammonia absorption, and inhibits growth of pathogens)
  • Stimulates proliferation of normal colon epithelial cells
  • Prevents proliferation and induces apoptosis of colorectal cancer cells
  • Affects gene expression of colon epithelial cells
  • Plays a protective role against colon cancer and colitis
  • Improves the gut barrier function by stimulation of the formation of mucin, antimicrobial peptides, and tight-junction proteins
  • Interacts with the immune system and regulates immune function
  • Has anti-inflammatory effects
  • Stimulates the absorption of water and sodium
  • Reduces oxidative stress in the colon
  • Assists in ion absorption
  • Assists in proper intestinal motility
  • Induces cell cycle arrest, differentiation, and apoptosis in colon cancer cells

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Figure 2.  The multiple effects of butyrate at the intestinal level.  (Source:  Potential beneficial effects of butyrate in intestinal and extra intestinal diseases)

Extra intestinal effects  13

  • Insulin sensitivity
  • Cholesterol synthesis
  • Energy expenditure
  • Ammonia scavenger
  • Stimulation of β-oxidation of very long chain fatty acids and peroxisome proliferation
  • CFTR function
  • Neurogenesis
  • HbF production

Tributyrin

The major problem with butyrate is achieving high concentrations in the blood. Butyrate is metabolized rapidly as soon as it enters the enteroocytes via its active transport system, and its plasma concentrations are far below those required to exert its antiproliferative/differentiating actions.  14 

An alternative and more advantageous form of butyric acid is the triglycerine form called Tributyrin, also known as glyceryl tributyrate. Tributyrin is a triglyceride containing 3 molecules of butyric acid which are bound by a glycerol molecule. 

Tributyrin is naturally present in butter in trace amounts.  However, it is not recommended to consume butter as a means to obtain therapeutic amounts of tributyrin.  There is no point to recommend consuming butter to someone if the intention is to increase butyric acid consumption.

As an alternative to consuming butter, tributyrin can now be consumed in the form of a supplement or a food additive and can provide considerable amounts of butyrate to the intestine in addition to the endogenous production of SCFAs (butyrate) from the fermentation of dietary fibers.

Tributyrin is known to overcome the pharmacokinetic drawbacks of butyrate.  Because it is rapidly absorbed and chemically stable in plasma, tributyrin diffuses through biological membranes and is metabolized by intracellular lipases, releasing therapeutically effective butyrate over time directly into the cell. 

Ball-and-stick model of the butyrin molecule

Figure 3.  Ball-and-stick model of the tributyrin molecule, the triglyceride of butyric acid.  Source:  By Jynto (talk) – Own workThis chemical image was created with Discovery Studio Visualizer., CC0, https://commons.wikimedia.org/w/index.php?curid=20234384

The technique of attaching butyrate to a glycerol molecule turns the new molecule (tributyrin) into a fat. The attachment of a glycerol molecule to 3 butyric acid molecules is through an ester bond which can only be broken by a specific enzyme called pancreatic lipase.  

Pancreatic lipase is secreted from the pancreas into the small intestine (duodenum) and not in the stomach.  Because of this, tributyrin stays intact in the stomach but once it reaches the small intestine (duodenum), the 3 butyric acid molecules are released by the pancreatic lipase enzyme. 

After the pancreatic lipase action, two free butyric acid molecules and one monobutyrin molecule are formed where they are used in the intestine and taken up by the enterocytes. After transportation through the portal vein they are metabolized in the liver. 

chem formula

Figure 4.  Ester bond of glycerol and 3 butyric acid molecules.  (Source: Bioremediation of Fats and Oils)

The tributyrin form of butyrate ensures high bioavailability of butyrate in all the sections of the small intestine.  Because tributyrin is a delayed release source of butyrate, it achieves more sustained plasma levels. 

According the the U.S. Federal Drug Administration (FDA), tributyrin is a food substance affirmed as Generally Recognized As Safe (GRAS).  15

Multiple Health Benefits of Tributyrin 

Specific studies on tributyrin have demonstrated multiple benefits in a number of disease conditions by releasing therapeutically effective butyrate over time directly into the cell.  The advantage with tributyrin is that it has all the health benefits of butyrate, as evidenced above, as well as its own specific targeted health benefits.

Some of the more important and specific health benefits of tributyrin include:

  • Anticarcinogenic potential
    • Colon cancer
    • Leukemia
    • Melanoma
    • Liver cancer (apoptosis)
  • Alzheimer’s disease and Dementia
  • Antibiotic-associated diarrhea (AAD)
  • Lipopolysaccharide (LPS)-induced liver injury
  • Inflammation

Anticarcinogenic potential

In vitro and in vivo studies have shown that tributyrin acts on multiple anticancer cellular and molecular targets without affecting non-cancerous cells. The mechanisms of action of tributyrin as a anticarcinogenic agent include:  16

  • the induction of apoptosis
  • cell differentiation
  • the modulation of epigenetic mechanisms

Due to the minimum toxicity profile of tributyrin, it is an excellent candidate for combination therapy with other agents for the control of cancer. 

Colon cancer

Tributyrin was shown to be more potent in inhibiting growth and inducing cell differentiation than natural butyrate on growth, differentiation and vitamin D receptor expression in Caco-2 cells, a human colon cancer cell line.  17

Tributyrin provides a useful therapeutic approach in chemoprevention and treatment of colorectal cancer.   

In another in vitro study, tributyrin showed potent antiproliferative, proapoptotic and differentiation-inducing effects in neoplastic cells.  18

Leukemia

In this study monobutyrin (MB) and tributyrin (TB) were studied in vitro for their effects on inducing differentiation of human myeloid leukemia HL60 cells and murine erythroleukemia cells. On a molar basis TB was about 4-fold more potent than either BA or MB for inducing differentiation of HL60 cells. BA, MB, or TB induced erythroid differentiation of murine erythroleukemia cells.  19

Melanoma

A study from February 2011 sought to investigate a possibility to develop tributyrin emulsion as a potent anti-cancer agent against melanoma. Tributyrin emulsion was more potent than butyrate in inhibiting the growth of B16-F10 melanoma cells. Accumulation of cells at sub G(0)/G(1) phase and the DNA fragmentation induced by tributyrin emulsion treatment revealed that tributyrin emulsion inhibited the growth of B16-F10 cells by inducing apoptosis. Treatment with tributyrin emulsion suppressed the colony formation of melanoma cells in a dose-dependent manner.  20

The data from this study suggests that tributyrin emulsion may be developed as a potent anti-cancer agent against melanoma.

Liver cancer

Researchers in this study from November 1999 investigated whether butyrate could induce apoptosis in transformed human liver (Hep G2) cells. Hep G2 cells treated with butyrate displayed acetylated histones, increased DNA fragmentation and morphological features consistent with apoptosis. 

They also investigated whether butyrate present in tributyrin, a triacylglycerol more compatible for inclusion into colloidal lipid structures than butyrate, could also induce apoptosis in Hep G2 cells.

Tributyrin induced DNA fragmentation and morphological features characteristic of apoptotic cells in Hep G2 cells.

These results are a significant advance towards delivering butyrate via colloidal lipid particles to cancerous sites in vivo. This study showed that butyrate and tributyrin are potent apoptotic agents. 21

Alzheimer’s disease and Dementia

Recent research at MIT has determined that, in rodent models of Alzheimer’s dementia, the negative impact of amyloid beta exposure on neuronal function and new memory formation results largely from increased neuronal expression of an enzyme known as HDAC2 (histone deacetylase 2).

A study from March 2004 showed that tributyrin may have the most practical potential to inhibit HDAC by blunting microglial activation. Tributyrin is anti-inflammatory in primary, brain-derived microglial cells.  A blunting of microglial cytokine production might in itself have a favorable impact on progression of Alzheimer’s.  22  23  

Antibiotic-associated diarrhea (AAD)

In a recent study from November 2014, researchers hypothesized that antibiotic-induced changes in gut microbiota reduce butyrate production, varying genes involved with gut barrier integrity and water and electrolyte absorption, lending to AAD, and that simultaneous supplementation with the probiotic Lactobacillus GG  and/or tributyrin would prevent these changes.

Optimizing intestinal health with Lactobacillus GG and/or tributyrin may offer a preventative therapy for AAD.  24  Lipopolysaccharide (LPS)-induced liver injury

In this study from April 2015, researchers elucidated the protective effect of oral administration of tributyrin against LPS-mediated lipid metabolism disorder in rats.  Tributyrin suppresses lipopolysaccharide (LPS)-induced liver injury through attenuating nuclear factor-κB activity with an increased hepatoportal butyrate level.  25

Inflammation

Another study from May 2015 was carried out to investigate the effects of tributyrin (TB) on the growth performance, pro-inflammatory cytokines, intestinal morphology, energy status, disaccharidase activity, and antioxidative capacity of broilers challenged with lipopolysaccharide (LPS).

Taken together, these results suggest that the TB supplementation was able to reduce the release of pro-inflammatory cytokines and improve the energy status and anti-oxidative capacity in the small intestine of LPS-challenged broilers.  26

ELiE Health Solutions

Tributyrin is now available for purchase by consumers and professionals directly from ELiE Health Solutions as a product called BUTYCAPS.

ELiE Health Solutions, based in Sevilla, Spain, was formed through a project based on the science of the microbiota and probiotics.

ELiE Health Solutions is named after Elie Metchnikoff, famed microbiologist and the recipient of the 1908 Nobel Price in Physiology. A century ago he proposed the benefit of acid lactic bacteria to the human host and their role in health and longevity.

David Manrique, a pharmacist with ELiE Health Solutions describes the challenges of finding a more bio-available form of butyric acid:

“The challenge was to find a chemical form of enteric release of butyric acid, and also to ensure microencapsulated as slowly and delayed release possible. It has been a great innovative effort, but we are very satisfied with the results.”  27 

ELiE Health Solutions was successful in developing a delayed release form of butyric acid (tributyrin) using microencapsulation technology in their product BUTYCAPS.  The microencapsulation technology of BUTYCAPS allows a slower and gradual release along the intestine. 

BUTYCAPS contains 900 mg of Tributyrin equivalent to 787 mg of butyric acid in each sachet. Each box contains 30 sachets.  BUTYCAPS are non-chewable granules.

170126_3dbutycaps

Figure 5.  BUTYCAPS product from ELiE Health Solutions

BUTYCAPS can be purchased directly from ELiE Health Solutions. 

Figure 6.  Formulation process of microencapsulated tributyrin. (Source:  ELiE Health Solutions)

Resources:

Purchase BUTYCAPS

Cover photo:  Enterocytes were butyrate is taken up in the intestine (Source)

The Multiple Health Benefits of Citrus Bergamot

Citrus Bergamot

Citrus bergamia Risso, also known as the bergamot orange or Citrus bergamot, is a fragrant citrus fruit the size of an orange, with a green color similar to a lime.  The word bergamot is etymologically derived from the Italian word “bergamotto”.

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Figure 1.  Citrus bergamot on the vine  (Source)

Citrus bergamot is a citrus plant that grows almost exclusively in the narrow coastal Calabria region in Southern Italy, due to sensitivity to the weather and soil conditions.   It is cultivated in Italy for the production of bergamot oil, a component of many brands of perfume and tea, especially Earl Grey tea. 

While bergamot is native to Italy, it is now widely distributed throughout the subtropical regions of China, including Guangdong, Guangxi, Fujian and Yunnan.

Image result for citrus bergamot

Figure 2.  Citrus Bergamot  (Source)

Genetic researchers have found that the bergamot orange is probably a hybrid of Citrus limetta and Citrus aurantium.

Citrus bergamia is sometimes confused with (but is not the same as):

  • Citrus medica (citron, the yellow fruit of which is also known as etrog)
  • Citrus limetta, the “sweet lemon” or “sweet lime”

Citrus Bergamot differs from C. Aurantium as Citrus Bergamot does not contain Synepherine, N-methyltyramine, and octopamine, which have been shown in research to constrict arteries, increase blood pressure, increase heart rate, cause heart-rhythm disorders, heart attack, and stroke.

Bio-Active Ingredients of Citrus Bergamot

The bio-active ingredients in citrus bergamot includes a unique profile of flavonoid and glycosides, such as:  1  2

  • brutieridin
  • melitidine
  • naringin
  • neodesmin
  • neoeriocitrin
  • neohesperidin
  • ponceritin
  • poncirin
  • rhoifolin
  • rutin

Health Attributes of Citrus Bergamot

A number of studies have shown the positive and powerful health attributes of citrus bergamot.  Among these attributes include:

  • anti-inflammatory  3
  • anti-hypertensive  4
  • hepatic protective effects  5
  • promotes digestion  6 

A clinical study found reduced total low-density lipoprotein, cholesterol, triglyceride and blood glucose levels in 237 patients who had taken oral BPF for 30 days.  7 

Moreover, the expression levels of two autophagy markers (LC3 II/I and Beclin-1) were increased while SQSTM1/p62 expression was reduced, indicating that BPF could stimulate autophagy.  8 

Naringin has been shown to be beneficial in animal models of atherosclerosis, while neoeriocitrin and rutin have been found to exhibit a strong capacity to prevent LDL from oxidation.

Brutieridine and melitidine has been shown to have the ability to inhibit HMG-CoA reductase.

Bergamonte®

Bergamonte® is an exclusive product produced by HP Ingredients which contains bioactive compounds of extract of the juice and albedo of citrus bergamia risso. 

HP Ingredients is a fasty growing innovative herbal and nutraceutical extract health company focused on bringing effective remedies from Asia, Italy, and Chile to the North American Market. HP Ingredients is dedicated to innovating new products and providing accurate and timely information on benefits of these well-researched extracts. We work closely with several teams of scientists from University of Malaysia and Forest Research Institute of Malaysia, the Universidad Austral de Chile, and the University Magna Graecia.

Bergamonte®, an extract of the bergamot orange, was shown in a double-blind, placebo-controlled study to:

  • Support the healthy balance of HDL to LDL cholesterol
  • Support healthy triglycerides and total cholesterol levels
  • Promote healthy blood sugar levels already in the normal range

Melitidine and Brutieridine

A published research article in the Journal of Natural Products 2009 showed that bergamot juice contained novel compounds with statin like principles, having the 3-hydroxy3-methylglutaric acid (HMG) found to the naringin (melitidine) and neohesperidin (brutieridine).

These novel compounds interfere with the natural synthesis of the cholesterol pathway in the human body: The HMG-CoA substrate interferes with the synthesis of the mevalonate acid, blocking the cholesterol production.

Superior Full-Spectrum Antioxidant ORAC Potency

Mode of Action

  • Inhibiting HMG-CoA Reductase
  • Inhibiting Phosphodiesterases PDEs
  • ‘Activating’ AMPK

Efficacy Findings from Clinical Trials

In an unpublished human clinical trial involving 192 patients, the following are the result after patients consumed 100ml of Citrus Bergamot juice for 30 days.

Hypolipemic and Hypoglycemic Activity of Bergamot Polyphenolic Fraction

Fitoterapia 82 (Nov 2011) 309–316
237 patients with hyperlipemia, hypercholesterolemic (HC, cLDL, low cHDL), mixed dyslipidemic (HC and TG), or metabolic syndrome (HC, HT, and HG) were taking either placebo, 500mg, 1000mg.

The effect of Bergamot Polyphenolic Fraction (500 and 1000 mg/daily) on reactive vasodilatation in patients suffering from isolated (HC) or mixed hyperlipidemia (HC/HT) and associated hyperglycemia (HC/HT /HG).

Bergamot Polyphenolic Fraction reduces total and LDL cholesterol levels (an effect accompanied by elevation of cHDL), triglyceride levels and by a significant decrease in blood glucose. Moreover, it  inhibited HMG-CoA reductase activity and enhances reactive vasodilation.

Supports healthy cholesterol level, increase LOX-1 expression and Protein Kinase B phosphorylation

International Journal of Cardiology, 2013
In this open-label, parallel group, placebo-controlled study, 77 patients were randomly assigned either placebo, Rosuvastatin, Bergamot Polyphenolic Fraction or combination of Bergamot Polyphenolic Fraction with Rosuvastatin for 30 days.

Both doses of rosuvastatin and Bergamot Polyphenolic Fraction help support healthy cholesterol level and reduce urinary mevalonate compared to control group. The benefits are associated with significant reductions of biomarkers used for detecting oxidative vascular damage, including malondialdehyde, oxyLDL receptor LOX-1 and phosphoPKB.

Effects on LDL Small Dense Particles, Metabolic Biomarkers, and Liver Function

Advances in Biological Chemistry, 2014, 4, 129-137
107 patients with metabolic syndrome and non fatty liver disease were given either placebo or 650 mg of Bergamot Polyphenolic Fraction twice a day for 120 days. Bergamot Polyphenolic Fraction group showed significant reduction in fasting plasma glucose, rotal cholesterol, LDL cholesterol, triglycerides, and increase of HDL cholesterol. Bergamot Polyphenolic Fraction decrease IDL particles by 51%, increase large LDL by 38%, decrease small LDL by 35%, and 20% increase of total HDL particles. Hepatorenal index was significantly reduced by 46%, accompanied by reduction of hepatic ultrosonographic pattern of steatosis by 99%. This suggests Bergamot Polyphenolic Fraction improves both liver function and inflammation as confirmed by reduction of TNF-α and CRP.

Product Comparison

Already within the normal range  

References
References
  1. Ross Walker, Elzbieta Janda and Vincenzo Mollace. The Use of Bergamot-derived Polyphenol Fraction in Cardiometabolic Risk Prevention and its Possible Mechanisms of Action. Cardiac Health and Polyphenols. Chp 84, Pg 1085-1103, 2014
  2. Micaela Gliozzi, Ross Walker, Elzbjeta Janda, Vincenzo Mollace. Bergamot polyphenolic fraction enhances rosuvastatin-induced effect on LDLcholesterol, LOX-1 expression and Protein Kinase B phosphorylation in patients with hyperlipidemia. International Journal of Cardiology Dec 2013, 170(2):140-5
  3. Vincenzo Mollace, Iolanda Sacco, Elzbieta Janda, Claudio Malara, Domenica Ventrice, Carmen Colica, Valeria Visalli, Saverio Muscoli. Hypolipemic and hypoglycaemic activity of bergamot polyphenols: From animal models to human studies. Fitoterapia 82 (2011) 309–316
  4. Celia C, Trapasso E, Locatelli M, Navarra M, Ventura CA, Wolfram J, Carafa M, Morittu VM, Britti D, Di Marzio L.. Anticancer activity of liposomal bergamot essential oil (BEO) on human neuroblastoma cells. Colloids Surf B Biointerfaces. 2013 Dec 1;112:548-53
  5. Delle Monache S, Sanità P, Trapasso E, Ursino MR, Dugo P, Russo M, Ferlazzo N, Calapai G, Angelucci A, Navarra M. Mechanisms underlying the anti-tumoral effects of Citrus Bergamia juice. PLoS One. 2013 Apr 16;8(4)
  6. Kang P, Suh SH, Min SS, Seol GH. The essential oil of Citrus bergamia Risso induces vasorelaxation of the mouse aorta by activating K(+) channels and inhibiting Ca(2+) influx. J Pharm Pharmacol. 2013 May;65(5):745-9
  7. Leopoldini M, Malaj N, Toscano M, Sindona G, Russo N. On the inhibitor effects of bergamot juice flavonoids binding to the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) enzyme. J Agric Food Chem. 2010 Oct 13;58(19):10768-73
  8. Di Donna L, De Luca G, Mazzotti F, Napoli A, Salerno R, Taverna D, Sindona G. Statin-like principles of bergamot fruit (Citrus bergamia): isolation of 3-hydroxymethylglutaryl flavonoid glycosides. J Nat Prod. 2009 Jul;72(7):1352-4
  9. Mollace V, Ragusa S, Sacco I, Muscoli C, Sculco F, Visalli V, Palma E. The protective effect of bergamot oil extract on lecitine-like oxyLDL receptor-1 expression in balloon injury-related neointima formation. J Cardiovasc Pharmacol Ther. 2008 Jun;13(2):120-9
  10. Natalizia Miceli, Maria Mondello, Maria Mondorte, Vasileios Sdrafkakis, Paola Dugo, Maria Crupi. Hypolipidemic effects of bergamot juice in rats Fed a Hypercholesterolemic Diet. J. Agric. Food Chem., Vol. 55, No. 26, 2007

Resistant Starch Produces Short-Chain Fatty Acids Which Benefits the Large Intestine

Resistant starch is a form of starch that is not digested and absorbed in the stomach and small intestine.  Instead it passes to the large intestine where it is fermented by the microbiota which confer numerous health benefits.  1

Resistant starch acts in similar ways to dietary fiber, yet it is not considered a dietary fiber.  It is considered more of a prebiotic substance since it serves as food for the large intestines microbiota.  Higher doses of resistant starch can cause flatulence.   2

There are five different types of resistant starch and can be viewed in the following Table.

There are a number of foods that naturally contain resistant starch.  Raw bananas and especially raw banana flour has the highest content of resistant starch.  The Table below lists those foods that contain resistant starch:

Resistant Starch in Various Foods

FoodServing sizeResistant starch (grams)
Banana flour, from green bananas1/4 cup, uncooked10.5-13.2
Banana, raw, slightly green1 medium, peeled4.7
Cold pasta1 cup1.9
Cold potato1/2" diameter0.6 - 0.8
Green peas, frozen1 cup, cooked4
High amylose RS2 corn resistant starch1 tablespoon (9.5 g)4.5
Lentils1/2 cup cooked2.5
Oatmeal1 cup cooked0.5
Oats, rolled1/4 cup, uncooked4.4
Pearl barley1/2 cup cooked1.6
White beans1/2 cup, cooked3.7
(Source: Resistant Starch Intakes in the United States)

When the three types of resistant starch, RSI, RSII and RSIII, are fermented by the large intestinal microbiota, short-chain fatty acids are produced.  There are seven short-chain fatty acids that are produced by the large intestine when it ferments dietary fiber and resistant starch.  Of these seven short-chain fatty acids, three of them are the most common:

  • acetate
  • propionate
  • butyrate

The most important short-chain fatty acid is butyrate.

Butyrate is a primary energy source for colonic cells.  3  4   Butyrate also has demonstrated anti-inflammatory properties.  5  Butyrate may also have a role in preventing certain types of colitis. A diet low in resistant starch and fiber, which will result in a low production of short-chain fatty acids in the colon, may explain the high occurrence of colonic disorders seen in the Western civilization.  6

Studies have demonstrated that butyrate has anti-carcinogenic properties:

  • It inhibits the growth and proliferation of tumor cell lines in vitro.  7
  • It induces differentiation of tumor cells, producing a phenotype similar to that of the normal mature cell.  8
  • It induces apoptosis or programmed cell death of human colorectal cancer cells.  9  10
  • It inhibits angiogenesis by inactivating Sp1 transcription factor activity and downregulating VEGF gene expression.  11

Resistant starch consistently produces more butyrate than other types of dietary fiber.   12  


Resources:

Wedo Banana Flour, 1 Pound

Bob’s Red Mill – Potato Starch, Gluten Free and Unmodified, 24 Ounces


Cover Photo by mauren veras

Lactobacillus reuteri NCIMB 30242 is a Heart Healthy Probiotic

Lactobacillus reuteri is a Gram-positive bacterium that is naturally found in the microbiome and is considered one of the most ubiquitous members of the naturally occurring gut bacteria.

Lactobacillus reuteri NCIMB 30242 or LRC™ is a unique superstrain of Lactobacillus reuteri that was initially developed by Micropharma Limited based in Canada.  In 2014, the U.S. company UAS Laboratories acquired the rights of this superstrain probiotic from Micropharma Limited.

Lactobacillus reuteri NCIMB 30242 is the first clinically proven heart health probiotic.  1

Clinical trials have been conducted with Lactobacillus reuteri NCIMB 30242 and the results were very promising for cardiovascular health.  The health benefits of Lactobacillus reuteri NCIMB 30242 include:

  • Supports healthy cholesterol already within normal range by reducing total cholesterol and LDL cholesterol
  • Supports healthy LDL particle size by supporting healthy apoB-100 (a marker for LDL particle number)
  • Promotes a healthy inflammatory response by supporting healthy C-reactive protein
  • Maintains healthy fibrinogen levels, helping to prevent blood clot formation
  • Supports and increases vitamin D levels (25-hydroxyvitamin D)
How L. Reuteri Helps The Body

Figure 1.  How L. Reuteri Helps the Body  (Source:  Life Extension Foundation: Unique Probiotic Targets Cardiovascular Disease)

Supports Healthy Total and LDL Cholesterol

In clinical trials, Lactobacillus reuteri NCIMB 30242 demonstrated an ability to support healthy cholesterol in adults already within the normal range.  2

It supports healthy total cholesterol and LDL-cholesterol levels in two ways:

  • By supporting the natural elimination of cholesterol, and
  • By helping to maintain the normal amount of cholesterol the body produces

Lactobacillus reuteri NCIMB 30242 produces an enzyme called bile salt hydrolase.  This enzyme breaks apart bile acids which are natural detergents made by the liver from cholesterol.  3  4

Supports Healthy LDL Particle Size

The size of LDL particles is governed by and influenced by a lipoprotein called apoB-100.  The particle size of LDL is critical to maintaining heart health.

Lactobacillus reuteri NCIMB 30242 has been shown to support healthy apoB-100 levels, which in turn may help to maintain healthy LDL particle size.  5

In one study of adults with elevated cholesterol, apoB-100 fell by 8% after consuming Lactobacillus reuteri NCIMB 30242.  6

Supports Healthy C-reactive protein (CRP) Levels

C-reactive protein (CRP) is a sensitive marker of inflammation that is used by medicine as a predictor of overall cardiovascular health. Lactobacillus reuteri NCIMB 30242 has been shown to support healthy CRP levels.  7

Maintains Healthy Fibrinogen Levels

Lactobacillus reuteri NCIMB 30242 has been shown to support healthy fibrinogen levels.  8

Increases Mean Circulating 25-hydroxyvitamin D

Oral supplementation with probiotic Lactobacillus reuteri NCIMB 30242 increases mean circulating 25-hydroxyvitamin D.  Lactobacillus reuteri NCIMB 30242 increased serum 25-hydroxyvitamin D by 14.9 nmol/L, or 25.5%, over the intervention period, which was a significant mean change relative to placebo of 17.1 nmol/L, or 22.4%, respectively (P = .003).  9  

Informational References:

UAS Labs  

Increasing Roseburia Bacteria in the Microbiome for Improved Gastrointestinal Health

Roseburia is a member of the phylum firmicutes and a Gram-positive anaerobic bacteria that inhabits the human colon.  Roseburia is a genus, or group, of five species of bacteria. It was named in honor of British-born American bacteriologist and author Theodor Rosebury.

 

Roseburia population in the gut can be increased or decreased by a number of factors like diet and antibiotic use.  Certain health conditions are affected by an increase or decrease of Roseburia:

Increase Abundance of Roseburia

  • Weight loss  1
  • Reduced glucose intolerance  2 

Decreased Abundance of Roseburia

  • Inflammatory bowel disease  3 
  • Ulcerative colitis  (decrease in Roseburia hominis)   4

One of the main functions of Roseburia is its ability to produce the short chain fatty acid called butyrate. 

Butyrate is an important food for the colonocytes which are the cells that line the colon.  The production of butyrate by certain beneficial bacteria, including Roseburia, provides energy for colon cells.  Without this energy source, colonocytes undergo autophagy and self-digest and die.  5 

Butyrate is produced by beneficial colonic bacteria feeding on or fermenting plant material with dietary fiber, otherwise known as prebiotics. 

Increasing Roseburia population in the Gut

In order to increase the population of Roseburia, it is necessary to feed the colon with the proper dietary fiber.  There are a number of dietary fibers that have been identified for their ability to raise Roseburia levels in the colon:

  • beta-glucan (mushrooms, oats) 6
  • chitin 7
  • green banana flour 8
  • inulin  9 

Informational References:

Modulating the Gut Microbiome: The Role of Probiotics & Prebiotics – Genova Diagnostics

Microbiome tests for Roseburia can be obtained from these companies:

Genova Diagnostics

Ubiome

MyMicroZoo

Faecalibacterium prausnitzii: The Peacekeeping Bacteria of the Gastrointestinal Tract

Faecalibacterium prausnitzii belongs to the phylum of Firmicutes and is one of the most abundant anaerobic bacteria in the human gut microbiota, with a proportion of around 5%-15% of total bacteria in feces.  It is named in honor of German bacteriologist Otto Prausnitz.

Relative abundance of Faecalibacterium prausnitzii is a biomarker of intestinal health in adults.

Function and Health Benefits of Faecalibacterium prausnitzii

Faecalibacterium prausnitzii plays a very important role in health benefits and biological functions.  Faecalibacterium prausnitzii:

  • Provides energy to the coloncytes to maintain intestinal health.  1
  • Controls inflammation through inflammatory-cytokine inhibition  2 
  • Protects against glucose intolerance and type 2 diabetes due to positive effects on insulin resistance  3
  • Produces and supplies the short chain fatty acid butyrate to the colonic epithelium  4
  • Has mucosal protective properties  5

Low and decreased levels of Faecalibacterium prausnitzii have been correlated with several pathological disorders, such as:

  • Crohn’s disease  6  7
  • Ulcerative colitis  8  9
  • Inflammatory Bowel disease (IBD)  10  11  12
  • Diabetes  13
  • Obesity  14
  • Asthma  15
  • Major Depressive Disorder  16 
  • Eczema  17
  • Atopic dermatitis  18

Faecalibacterium prausnitzii is also known to be very sensitive to oxidative stress which means that high levels of free radicals kill off this bacteria.

Image result for Faecalibacterium prausnitzii

Source:  Philippe Langella: “Commensal Bacteria and Recombinant Lactic Acid Bacteria as Novel Probiotics for Human Intestinal Health”

Increasing the Population of Faecalibacterium prausnitzii in the Gut Microbiome

Currently there is no probiotic supplement that contains Faecalibacterium prausnitzii.  Therefore, the most important and primary way to increase Faecalibacterium prausnitzii is to increase the consumption of fiber in the diet.  19

Various studies show that a high fermentable fiber with a low glycemic index will increase Faecalibacterium prausnitzii.  20  The following fibers have been shown to increase the population of Faecalibacterium prausnitzii:

  • Sumac-sorghum  21
  • Galacto-oligosaccharides (GOS)  22  23
  • Apple Pectin  24 
  • Inulin  25  26
  • Fructo-oligosaccharides (FOS)  27 

There are other methods to increase the population of Faecalibacterium prausnitzii, such as:

  • Calorie restriction and fasting  28
  • Riboflavin (Vitamin B2) supplementation 29
    • patented formula containing riboflavin for the selective stimulation of Faecalibacterium prausnitzii in the gastrointestinal tract  30 
  • Uronic Acids (glucuronic acid or Calcium D-Glucurate)  31
  • Grape polyphenols  (grape seed extract)  32
  • Bacillus coagulans GBI-30  (6086 (BC30); GanedenBC(30)  33

Seminar: "Commensal Bacteria as Novel Probiotics for Human Intestinal Health" (Philippe Langella)

The Human Gut Microbiome - Its Impact on Our Lives and Our Health

Informational References:

The following companies can test for levels of Faecalibacterium prausnitzii in your gut microbiome:

Genova Diagnostics – GI Effects® Comprehensive Profile – Stool

uBiome – Gut Explorer

MVZ Institute for Micro Ecology GmbH – KyberKompakt Pro

Increasing and Maintaining Akkermansia muciniphila for a Healthy Gut Microbiome

Introduction to Akkermansia muciniphila

Akkermansia muciniphila (Akkermansia) is a Gram-negative, anaerobic, non-spore-forming and oval-shaped bacterium.  It is a member of the Verrucomicrobia phylum and is part of the human commensal bacterium. 

It was isolated in 2004 and named after Dr. Antoon Akkermans, a dutch microbiologist.  The word muciniphila is derived from the Latin and Greek words for mucin loving, where phila (philos) is loving.

Akkermansia is abundantly present in the healthy human intestinal tract, making up to 1-5% of the microbial community of the colon.  1  It is very important to human health that the population of Akkermansia is high and not depleted, since its abundance inversely correlates with body weight and type 1 diabetes in mice and humans. 

Akkermansia plays a crucial role in the mutualism between the gut microbiota and host that controls gut barrier function and other physiological and homeostatic functions during the following conditions:

  • diabetes  2
  • inflammation  3 
  • obesity  4 

Akkermansia Colonizes the Mucus Layer of the Colon

The gastrointestinal tract is covered with a layer of mucus which serves, among other things, as a source of nutrients for bacterial growth.  5  This mucus layer attracts bacteria which colonize, survive and multiple inside and on the mucus layer.  Akkermansia is the most abundant mucus degrading bacteria in the healthy individual. 

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Akkermansia muciniphila activity and interactions in the intestine. Schematic overview of the metabolic activities of A. muciniphila in the gut and the microbiota and host response as a result of A. muciniphila colonization. As a result of mucus degradation, A. muciniphila produces oligosaccharides and SCFAs. These products can stimulate microbiota interactions and host response. Oligosaccharides and acetate stimulate growth and metabolic activity of bacteria that colonize close to the mucus layer. This may provide colonization resistance to pathogenic bacteria that have to cross the mucus layer to reach the intestinal cells. The propionate produced by Akkermansia-like bacteria can signal to the host via the Gpr43 receptor and other SCFA may also do the same via Gpr41 (Le Poul et al., 2003; Maslowski et al., 2009). This may trigger a cascade of responses in the host expression machinery and together with other signaling pathways has shown to result in immune stimulation and metabolic signaling in monoassociated germ-free mice (Derrien et al., 2011). Source: Microbes inside—from diversity to function: the case of Akkermansia

Mucus production and thickness is important to a healthy gastrointestinal tract and Akkermansia is key in this process.  The host and Akkermansia communicate continually and create a positive feedback loop in which Akkermansia degrades the mucus layer which stimulates new mucus production and the the production of new mucus stimulates growth of Akkermansia.  This process assures that abundant amounts of Akkermansia maintain the integrity and shape of the mucus layer.  6

Low population levels of Akkermansia indicates a thin mucus layer.  This results in a weakened gut barrier function and the ability of toxins to translocate into the bloodstream.

Akkermansia Produces Important Metabolites

As a result of the mucus degradation process, Akkermansia produces two very important short chain fatty acids:  7

  • acetate
  • propionate

These short chain fatty acids trigger a cascade of responses in the host resulting in immune stimulation and metabolic signaling.  8

Studies have indicated that Akkermansia has an anti-inflammatory role in two gastrointestinal conditions: 

  • appendicitis  9 
  • inflammatory bowel disease  10 

Increasing Akkermansia muciniphila

At the present moment (January 2017), there is no commercially available probiotic supplement that contains Akkermansia muciniphila.  Instead, increasing Akkermansia muciniphila can be accomplished through the consumption of certain prebiotics and foods.

Increasing Akkermansia colonization of the colon can be promoted by the administration of prebiotic substrates, including:

  • arabinoxylan  11
  • inulin  12
  • fructooligosaccharides (FOS) (oligofructose) (increased the abundance of Akkermansia muciniphila by ∼100-fold in mice)  13

Akkermansia can also be increased by consuming polyphenol-rich foods, including:

  • pomegranate (attributed to ellagitannins and their metabolites) 14
  • grape polyphenols (grape seed extract) (proanthocyanidin-rich extracts may increase mucus secretion, therefore creating a favorable environment for Akkermansia to thrive)  15  16
  • cranberries  17

Certain foods and fats can increase the abundance of Akkermansia:

Navy beans have been shown to increase Akkermansia abundance.  Fecal abundance of Akkermansia muciniphila, whose abundance is inversely related to the severity of the obese phenotype, was increased in the high fat + bean diet group versus high fat diet by 20-fold.  18

Mice fed fish oil compared to lard for 11 weeks confirmed the increase in Akkermansia and Lactobacillus in the cecal contents.  19

The first-line medication for type 2 diabetes, Metformin, has been shown to significantly increase the relative abundance of Akkermansia in HFD-Met mice.  20

Informational References:

The following companies can test for levels of Akkermansia in your gut microbiome:

Genova Diagnostics – GI Effects® Comprehensive Profile – Stool

uBiome – Gut Explorer

Propionibacterium freudenreichii: A Probiotic With Remarkable and Promising Properties

Introduction to Propionibacteria and Propionibacterium freudenreichii

Propionibacterium freudenreichii belongs to the dairy group of the genus Propionibacterium.  Propionibacteria were first described at the end of the 19th century by E. von Freudenreich and S. Orla-Jensen, who were studying propionic acid fermentation in Emmental cheese (Swiss cheese), leading to propose the genus Propionibacterium.  1  Propionibacteria belongs to the phylum of firmicutes. They are characterised as gram-positive, non-sporing, non-motile pleomorphic rods. They are anaerobic to aerotolerant and generally catalase positive.

The genus Propionibacterium is divided in two groups based on habitat of origin:

classical or dairy propionibacteria (mainly isolated from dairy products such as cheese)

  • Propionibacterium acidipropionici
  • Propionibacterium microaerophilum
  • Propionibacterium cyclohexanicum
  • Propionibacterium freudenreichii subspecies freudenreichii
  • Propionibacterium jensenii
  • Propionibacterium freudenreichii subspecies shermanii
  • Propionibacterium thoenii

cutaneous propionibacteria (typically found on skin, also named “acnes group”)

  • Propionibacterium acidifaciens 
  • Propionibacterium acnes 
  • Propionibacterium australiense
  • Propionibacterium avidum
  • Propionibacterium granulosum
  • Propionibacterium propionicum

The dairy propionibacteria species are considered safe whereas cutaneous Propionibacterium species are pathogens.

The dairy propionibacteria do not normally belong to the human microbiota but can be isolated from various habitats including raw milk, dairy products, soil and fermenting food.  Dairy propionibacteria are used in the dairy industry as starter cultures for ripening Swiss cheeses, particularly in the creation of Emmental cheese, and to some extent, Jarlsberg cheese, Leerdammer and Maasdam cheese.  2  Industrial applications of Propionibacterium freudenreichii include production of vitamin B12 (cobalamin), propionic acid, trehalose and conjugated linoleic acid.  

Criteria for the Use of Propionibacterium freudenreichii

Dairy propionibacteria offer good prospects for their use as human probiotics due to the following qualities:  3

  • safety
  • gastrointestinal transit survival
  • adherence to intestinal cells and mucosa

Safety

Consumption of propionibacteria is considered safe since it is contained in Emmental cheese which is consumed worldwide.  It is estimated that Emmental cheese contains up to 1,000,000,000 (109) propionibacteria per gram.

In addition to its widespread consumption from Emmental cheese, Propionibacterium freudenreichii has received the “Generally Recognised As Safe” (GRAS) status and has been granted “Qualified presumption of safety” (QPS) status from the European food safety authority.

Lastly, there are no indication of side effects from consuming dairy propionibacteria that have been reported in any of the human trials.

Gastrointestinal transit survival

Dairy propionibacteria have shown good constitutional survival under digestive stress and their ability to survive low pH conditions of the stomach and exposure to bile.  4  Promising results of gut survival of dairy propionibacteria has been demonstrated in vivo in humans.  5

It is also evident that dairy propionibacteria has strong survival potential due to its role in the cheese making process, which imposes certain technological stressors on the bacteria. 

High levels of propionibacteria has been detected in feces which provides further proof that it can survive gastrointestinal transit.  Once consumption of the dairy propionibacteria ceased, levels in the feces declined.

Adherence to intestinal cells and mucosa

Dairy propionibacteria are able to adhere to immobilised mucus.  6  7  When Lactobacillus rhamnosus GG was added to Propionibacterium freudenreichii ssp. shermanii JS the adhesion to intestinal mucus of Propionibacterium freudenreichii ssp. shermanii JS increased from 1.9 to 2.3%.  8 

Dairy propionibacteria also adheres in vitro to human intestinal epithelial cell lines.  9  10

Mechanism of Propionibacterium freudenreichii

Propionibacterium freudenreichii ferments and converts lactate to form:

  • propionic acid (which favors the growth of bifidobacteria)  11 
  • acetic acid
  • carbon dioxide

In effect, Propionibacterium freudenreichii functions as a prebiotic in the colon by generating short-chain fatty acids (SCFA).  SCFA’s are powerful protectors of the large intestine since they:  12

  • protect the intestinal lining
  • down-regulate NF-κB (nuclear factor-kappa B)
  • support absorption of calcium, magnesium and potassium

Propionibactera also have profound probiotic effects.  These effects include:

  • production of bacteriocins  13
  • secretion of anti-fungal compounds  14  
  • secretion of anti-viral compounds  15
  • synthesis of vitamin B8 (biotin), B9 (folic acid) and B12 (cobalamin)  16  17
  • production of trehalose  18
  • production of conjugated linoleic acid  19
  • growth stimulation of other beneficial bacteria, like bifidobacteria  20
  • creation of a high level of β-galactosidase (lactase) activity  21
  • inhibition of beta-glucuronidase activities 22
  • reduction in pathogen adhesion to immobilised mucus  23
  • ability to aggregate with pathogenic bacteria  24
  • inhibition of Helicobacter pylori adhesion to a human intestinal epithelial cell line  25
  • ability to survive during gastric digestion

Propionibacterium freudenreichii produces a Bifidogenic Growth Stimulator (BGS) named ACNQ which selectively enhances the utilization of Oligosaccharides by Bifidobacteria.  A placebo-controlled study of the effects of BGS on fecal flora and stool frequency was carried out in healthy human subjects. A drink with the sterilized ET-3 culture was administered once a day for 7 days. Bifidobacterium percentage in the fecal flora and stool frequency were significantly increased by administration of the P. freudenreichii culture. The ACNQ exhibited growth stimulation of bifidobacteria at an extremely low concentration and enhanced the activities of NADH oxidase and NADH peroxidase in bifidobacteria. These ACNQ-mediated reactions seem to play roles in NAD (P) +-regeneration processes and seem to be responsible for the growth stimulation of bifidobacteria.   26  27 

Propionibacterium freudenreichii seems to grow and perform in conjuction with another probiotic called Lactobacillus helveticus, even though Propionibacterium freudenreichii does not need Lactobacillus helveticus to work and flourish.  Lactobacillus helveticus releases amino acids and peptides that Propionibacterium freudenrechii utilize.  28 

Bifidobacterium is one of the most researched genus of the human microbiota that is used for probiotic purposes. The primary interest in Propionibacterium freudenreichii in the scientific research is its potential to enhance the indigenous bifidobacteria population. 29

The in vivo experiements with Propionibacterium freudenreichii resulted in modulation of the gastrointestinal microbiota by decereasing Clostridium and Bacteroides.  30

Propionibacterium freudenreichii produces Trehalose in the colon which has been observed to reduce the level of enterohaemorrhagic Escherichia coli O157:H7.  31  

Propionibacterium freudenreichii as a Chemopreventive Agent

Propionibacterium freudenreichii demonstrates great promise in acting as a chemopreventive and chemoprotective agent.  These attributes are accomplished through a number of mechanisms:

  • antimutagenic properties preventing mutations caused by various mutagenic agents  32
  • ability to bind, in vitro, carinogenic compounds:
    • mycotoxins  33
    • cyanotoxin microcystin-LR  37
    • plant lectins – concanavilin and jacalin  38
  • ability to bind to heavy metals
    • cadmium  39
    • lead  40
  • induces NKG2D ligand expression on human-activated T lymphocytes and cancer cells  41
  • ability to lower and inhibit  beta-glucuronidase which is a risk factor for carcinogenesis  42

A number of research studies have shown that Propionibacterium freudenreichii is effective therapeutically in various cancers, especially colon cancer.  Table 1 lists the various cancers that have been treated with Propionibacterium freudenreichii:

Table 1: Propionibacterium freudenreichii Effects on Various Cancers

CancerAbstractReference
Breast cancer
To determine whether the purified 9c,11t conjugated linoleic acid (CLA) isomer, the main dietary isomer, is biologically active on mammary tumor growth, we carried out a dietary intervention study designed to compare its effects with those of a mixture of CLA isomers on the incidence and growth of autochthonous mammary tumors induced by methylnitrosourea in rats.1
Colon cancer
Furthermore, propionibacteria were able to decrease the proliferation index in the distal colon after treatment with DMH (P 2
Propionibacteria induce apoptosis of colorectal carcinoma cells via short-chain fatty acids acting on mitochondria3
The human probiotic Propionibacterium freudenreichii kills colorectal adenocarcinoma cells through apoptosis in vitro via its metabolites, the short chain fatty acids (SCFA), acetate and propionate.4
The bacterial enzymes beta-glucosidase, beta-glucuronidase, and urease may contribute to the development of colon cancer by generating carcinogens. A reduction in the activity of these enzymes by certain lactic acid bacteria is considered to be beneficial. This study examined fecal beta-glucosidase, beta-glucuronidase, and urease activities during administration of Lactobacillus rhamnosus LC705 (LC705) together with Propionibacterium freudenreichii ssp shermanii JS (PJS).5
Stomach cancer
This study investigated the potential for butyrate and propionate to alter cell viability, cell cycle regulation and intracellular protective mechanisms in a human gastric cancer cell line (Kato III). Kato III cells were incubated with butyrate or propionate for 24, 48 and 72 hr.6

Propionibacterium Effects on Various Disease and Conditions

Propionibacterium freudenreichii and other strains of propionibacterium have demonstrated promising properties in treating and preventing a number of conditions and diseases, especially those of the colon such as Irritable Bowel Syndrome and Colitis.  Table 2 lists the various conditions and diseases that have been studied using Propionibacterium freudenreichii and other strains of propionibacterium:

Table 2: Propionibacterium freudenreichii Effects on Various Disease and Conditions

DiseaseAbstractReference(s)
Allergies
In a double-blinded, placebo-controlled study we randomized 1223 mothers with infants at high risk for allergy to receive a probiotic mixture (2 lactobacilli, bifidobacteria, and propionibacteria) or placebo during the last month of pregnancy and their infants to receive it from birth until age 6 months.1
Colitis
Experimental studies have shown that luminal antigens are involved in chronic intestinal inflammatory disorders. Bifidogenic growth stimulator (BGS) is a prebiotic preparation produced by Propionibacterium freudenreichii isolated from Swiss cheese. Previously BGS was shown to act in the colon as a growth stimulator of Bifidobacteria. This study investigated the efficacy and safety of BGS in the treatment of ulcerative colitis.2
Milk whey culture with Propionibacterium freudenreichii is a prebiotic preparation isolated from Swiss cheese. It selectively stimulates the growth of Bifidobacteria through the action of its component 1, 4-dihydroxy-2-naphthoic acid. Recent reports have shown that this foodstuff ameliorates experimental colitis and human ulcerative colitis. We discuss the characteristics and the therapeutic application of this foodstuff for patients with ulcerative colitis.3
The anti-inflammatory mechanism of prebiotics has recently been shown to have an impact on the host immune system. DHNA from Propionibacterium freudenreichii is known to promote the proliferation of Bifidobacterium and can ameliorate colitis, although its mode of action remains unknown.4
1.4-Dihydroxy-2-naphthoic acid (DHNA), a bifidogenic growth stimulator from Propionibacterium freudenreichii, is thought to have a beneficial effect as a prebiotic; however, its in vivo effect on intestinal inflammation remains unknown. The aim of this study was to determine whether oral administration of DHNA can ameliorate dextran sodium sulphate (DSS) induced colitis and to determine the possible underlying mechanisms.5
Colonic infusion with Propionibacterium acidipropionici reduces severity of chemically-induced colitis in rats6
This study aimed to evaluate whether milk whey culture with Propinibacterium freudenreichii ET-3 (milk whey culture), which has been reported to have Bifidogenic activity, is effective on the colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in rats.7
Inhibits Candida
R eport that a cheese containing a mixture of probiotics ( L. rhamnosus GG, L. rhamnosus LC705 and P. freudenreichii ssp. shermanii JS) reduced the risk of high yeast counts, especially Candida sp., in the mouth of elderly people.8
Constipation
The effects of fermented milk whey containing novel bifidogenic growth stimulator (BGS) produced by Propionibacterium on fecal microflora, putrefactive metabolite, defecation frequency and fecal properties were studied in 18 senile volunteers (64-102 yr age) needed serious nursing-care taking enteral nutrition by tube feeding. The test powder food containing 0.4 g/day of freeze-dried BGS were given for 4 weeks. During BGS intake, defecation frequency and fecal quantity were increased significantly, the ratio of color of dark brown and strong odor of feces were decreased significantly.9
Some relief from constipation may be observed with the combination of L. rhamnosus/P. freudenreichii. This probiotic combination also reduced fecal enzyme activity. The tested probiotics did not affect the mucosal barrier.10
Immunomodulation
Immunomodulatory properties of 10 dairy propionibacteria, analyzed on human peripheral blood mononuclear cells (PBMCs), revealed a highly strain-dependent induction of anti-inflammatory cytokine interleukin 10 (IL-10). Two selected strains of Propionibacterium freudenreichii showed a protective effect against two models of colitis in mice, suggesting a probiotic potential predicted by immune-based selection criteria for these cheese starter bacteria.11
The development of a dairy Propionibacterium and its establishment in the gut were studied. Mice fed a conventional diet received a suspension of propionibacteria in skim milk provided in their water bottles for 7 d. Counts of propionibacteria in faeces and intestinal sections indicated that the strain used reached significant levels in the gut during treatment.12
It was observed that Lactobacillus casei was able to stimulate phagocytosis both by the cell wall and the peptidoglycan, whereas it did not produce changes in IgA. L. acidophilus, on the other hand, produced an increase in the levels of IgA without modifying phagocytosis. Propionibacterium acidipropionici only showed immunostimulating activity with the cell wall, but not with the peptidoglycan.13
Immunomodulation by probiotics is a subject of growing interest, but the knowledge of dose response and time profile relationships is minimal. In this study we examined the effects of Lactobacillus rhamnosus GG (LGG) and Propionibacterium freudenreichii subsp. shermanii JS (PJS) on the proliferative activity of murine lymphocytes ex vivo.14
The efficacy of Propionibacterium jensenii 702 to stimulate a cell-mediated response to orally administered soluble Mycobacterium tuberculosis antigens using a mouse model15
Immunomodulatory properties of 10 dairy propionibacteria, analyzed on human peripheral blood mononuclear cells (PBMCs), revealed a highly strain-dependent induction of anti-inflammatory cytokine interleukin 10 (IL-10). Two selected strains of Propionibacterium freudenreichii showed a protective effect against two models of colitis in mice, suggesting a probiotic potential predicted by immune-based selection criteria for these cheese starter bacteria.16
Feeding synbiotics to newborn infants was safe and seemed to increase resistance to respiratory infections during the first 2 years of life.17
Inhibits H. Pylori
The aims of this study were (i) to evaluate the effect of recommended antimicrobial treatment of Helicobacter pylori infection, consisting of clarithromycin, amoxicillin and lansoprazole, on intestinal microbiota and (ii) to determine the ability of a probiotic combination containing Lactobacillus rhamnosus GG, L. rhamnosus LC705, Propionibacterium freudenreichii ssp. shermanii JS and Bifidobacterium breve Bb99 to prevent treatment-induced alterations in the intestinal microbiota.18
We characterize four probiotics and their combination in terms of pathogen adhesion, barrier function, cell death, and inflammatory response in Helicobacter pylori-infected epithelial cells. H. pylori-infected Caco-2 cells were pretreated with Lactobacillus rhamnosus GG, Lactobacillus rhamnosus Lc705, Propionibacterium freudenreichii subsp. shermanii Js, Bifidobacterium breve Bb99, or all four organisms in combination.19
Inflammation and IBD
P robiotic intervention with P. freudenreichii subsp. shermanii JS in healthy adults led to a reduction in the serum level of C-reactive protein (CRP) compared to a placebo control.20
All tested bacteria induced TNF-alpha production. The best inducers of Th1 type cytokines IL-12 and IFN-gamma were Streptococcus and Leuconostoc strains. All Bifidobacterium and Propionibacterium strains induced higher IL-10 production than other studied bacteria.21
Effects of probiotic Lactobacillus rhamnosus GG and Propionibacterium freudenreichii ssp. shermanii JS supplementation on intestinal and systemic markers of inflammation in ApoE*3Leiden mice consuming a high-fat diet22
After the screening of microorganism culture, the culture of Propionibacterium freudenreichii ET-3 in the milk whey (milk whey culture) was found to stimulate the growth of our own Bifidobacteria in the colon but not the growth of other microorganisms.23
Our aim was to determine whether IBS-associated bacterial alterations were reduced during multispecies probiotic intervention consisting of Lactobacillus rhamnosus GG, L. rhamnosus Lc705, Propionibacterium freudenreichii ssp. shermanii JS and Bifidobacterium breve Bb99. The intervention has previously been shown to successfully alleviate gastrointestinal symptoms of IBS.24
To investigate the effects of multispecies probiotic supplementation (Lactobacillus rhamnosus GG, L. rhamnosus Lc705, Propionibacterium freudenreichii ssp. shermanii JS and Bifidobacterium animalis ssp. lactis Bb12) on abdominal symptoms, quality of life, intestinal microbiota and inflammatory markers in irritable bowel syndrome.25
To investigate the mode of action of a multispecies probiotic consisting of Lactobacillus rhamnosus GG, Lactobacillus rhamnosus Lc705, Propionibacterium freudenreichii ssp. shermanii JS and Bifidobacterium breve Bb99 by monitoring its effects on intestinal microbiota and markers of microbial activity.26
I rritable bowel syndrome (IBS) is one of the most common diagnoses in gastroenterology, but current therapies are inefficient. Recent clinical trials suggest beneficial effects of certain probiotics in IBS. Because of the heterogeneity of IBS a probiotic combination may be more efficient than a single strain. We screened for optimal strains, and developed a multispecies probiotic combination consisting of L. rhamnosus GG, L. rhamnosus Lc705, P. freudenreichii ssp. shermanii JS and Bifidobacterium breve Bb99.27

Probiotics Supplements: Should They Be Taken With Or Without Food?

There exists some apparent ambiguity among health professionals on whether to take probiotic supplements with or without food.  The product labels of various probiotic manufacturors may contradict each other by advising to take their probiotic product before meals, during meals or after meals or even without meals.  These contradictions lead to confusion within the health industry and for the consumer.

Advocates in favor of taking probiotic supplements on an empty stomach state that there are no digestive enzymes and bile acids that can damage the probiotics.  The water taken with the probiotics supposedly dilute the acid in the stomach and quickly transport the probiotic into the small intestine.

Opposing advocates argue that the stomach acid in a fasting state (empty stomach) has a lower stomach acid pH than when the stomach is filled with food, and that a lower stomach acid pH rapidly kills probiotics.  The lower the stomach acid pH, the more detrimental to the probiotic, as stomach acid kills the live microorganisms.

When the stomach is empty (in a fasted state), the gastric (stomach acid) pH is in the range of 0.8 to 3.0.  The lower number of this range can be as high as 1.3. 

After eating food, gastric pH can raise to as high as 4.0-5.8, and can be as high as 7.0.  1  Within 1 hour after eating, the pH of the stomach decreases to less than 3.1.  The quantity, food pH value and composition of the food eaten plays a major role in the time required to re-store the fasting pH levels.

Researchers in 1990 set out to measure the pH in the upper gastrointestinal tracts of young, healthy men and women in the fasting state and after administration of a standard solid and liquid meal.  

In the fasted state, the median gastric pH was 1.7. When the meal was administered the gastric pH climbed briefly to a median peak value of 6.7, then declined gradually back to the fasted state value over a period of less than 2 hours.   2

When probiotic supplements are taken with a meal, the food buffers stomach acid thereby providing increased protection for the probiotics.  Some foods, like high fiber foods, (vegetable and certain fruits) can also nourish the probiotics in the gastrointestinal tract by supplying fermentable substrates. 

The advocates of taking probiotic supplements with food also would remind you that before the invention and production of probiotic supplements, individuals obtained their probiotics in foods, usually fermented foods, like yogurt, kefir and sauerkraut.  The probiotics in these foods were consumed with and as part of the food.

The question may have been answered in 2011, when a team of researchers examined the impact of the time of administration with respect to mealtime and the impact of the buffering capacity of the food on the survival of probiotic microbes during gastrointestinal transit.

In their experiment they used a probiotic that contained four strains:

  • Lactobacillus helveticus R0052
  • Lactobacillus rhamnosus R0011
  • Bifidobacterium longum R0175
  • Saccharomyces cerevisiae boulardii (non-pathogenic yeast)

Enumeration during and after transit of the stomach and duodenal models showed that survival of all the bacteria in the product was best when given with a meal or 30 minutes before a meal (cooked oatmeal with milk). Probiotics given 30 minutes after the meal did not survive in high numbers.

What they found important for the survival of the probiotics was the fat content of the meal and not so much the protein content.  They used milk with 1% milk fat and oatmeal-milk gruel.  This fat content meal had a better result than water or apple juice.

They concluded that ideally, non-enteric coated bacterial probiotic supplements should be taken with or just prior to a meal containing some fats.  3

It is also important to note that probiotic supplements should not be taken with hot foods or beverages since the excessive heat can kill the probiotics.

NutritionFacts.org - Should Probiotics Be Taken Before, During, or After Meals?