Host of Bacteria in Fermented Dairy Products acting in conjunction with the Gut Bacteria take care of Gut and Body Health

Fermented dairy products like yogurt and cheese contain a number of genera of bacteria called probiotics having beneficial effect on human gut. They are  members of the genera Lactobacillus, Lactococcus, Leuconostoc, Enterococcus, Pediococcus, Streptococcus, Staphylococcus and bifidobacterium.

There are 100 trillion (10¹²) of microbes in the mammalian intestines. They live in the human gut and help in many ways; some of those are responsible for fermentation of resistant dietary fibers, which are otherwise indigestible by gut enzymes in human. Those are also called as commensals.

Adopted from PNAS

Some commensals are involved in the fermentation of dietary fibers in the colon leading to production of short chain fatty acids (SCFAs), 2-carbon to 5-carbon weak acids including acetate (C2), propionate (C3), butyrate (C4) and valerate (C5). Among the SCFAs, butyrate has received particular attention for its multiple beneficial effects from the intestinal tract to the peripheral tissues.

The most important butyrate producers appear to be Faecalibacterium prausnitzii, which belongs to the Clostridium leptum (or clostridial cluster IV) cluster, and Eubacterium rectale/Roseburia spp., which belong to the Clostridium coccoides (or clostridial cluster XIVa) cluster of firmicute bacteria.

Butyrates can be produced from lactate in gut by the microbiota. Lactic acid producing bacteria like Lactobacillus and bifidobacterium are found in fermented dairy products. Thus, a lower PH or an acidic environment in gut may be a better place for butyrate producing bacteria.

The SCFAs have anti-inflammatory effect in the gut. Though the exact mechanism has not been established, it is thought that the SCFA have immunomodulatory effects on colonic macrophages, which are important cell types responsible for inflammation.

It has been found out by the researchers that n-butyrate silences genes responsible for expression of pro-inflammatory mediators including Nos2, Il6, Il12a, and Il12b.

The host immune system must constantly maintain a balance between tolerance to commensals and immunity against pathogens to avoid unnecessary immune responses against otherwise harmless bacteria in the intestine.

Adopted from PNAS

In a study, researchers have demonstrated that n-butyrate regulates macrophage function through the inhibition of Histone Deacylases (HDACs). HDACs keep genes in compact form, preventing uncoiling; when inhibited, there occurs uncoiling of chromatin, a step that proceeds for gene expression (Transcription).

Butyrate induced histone acylation results in production of factors that down-regulate certain gene expression that are harmful; whereas up-regulate function of another set of genes that have protective effect.

The precise mechanism proposed is the transcriptional up-regulation of detoxifying enzymes, such as glutathione-S-transferase (GST). The modulation of the GST gene may protect cells from genotoxic carcinogens, such as H₂O₂ and 4-hydroxynonenal (HNE). There occurs suppression of nuclear factor κB (NFkB) activation, the inhibition of interferon γ production and the upregulation of peroxisome proliferator-activated receptor γ (PPARγ).

As a result, intestinal macrophages reduce production of pro-inflammatory mediators such as NO, IL-6, and IL-12. Butyrate induces anergy in intestinal macrophages making immune system hypo-responsive to the beneficial, n-butyrate–producing bacteria.

In the absence of these beneficial bacteria, lamina propria macrophages remodel the intestinal microbial communities by eliminating unwanted populations of bacteria through the production of pro-inflammatory mediators until the optimal microbial balance is re-achieved and the levels of n-butyrate return to the desired concentrations.

Misregulated responses can lead to inflammatory bowel diseases such as ulcerative colitis or Crohn’s disease.

Intervention studies in patients with ulcerative colitis (UC) suggested that the luminal administration of butyrate or stimulation of luminal butyrate production by the ingestion of dietary fibers results in an amelioration of the inflammation and symptoms.

Hallert et al. instructed 22 patients with quiescent UC to add 20 g of dietary fibers to their daily diet. A total of 4 weeks of this treatment resulted in a significant increase of fecal butyrate concentration and in a significant improvement of abdominal symptoms.

Vernia et al. in a double-blind, placebo-controlled multicenter trial, treated 51 patients with active distal UC with rectal enemas containing either 5-aminosalicylic acid (5-ASA) or 5-ASA plus sodium butyrate (80 mM, twice a day). The combined treatment with topical 5-ASA plus sodium butyrate resulted in a significant improvement of the disease activity score compared to that observed in patients treated with 5-ASA alone.

Fermented dairy products (low fat) along with adequate amount of dietary fiber (Resistant, available from whole wheat, green banana, onion, peas and beans etc.) may benefit gut/body health acting together.

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Food and Gut Microbes Acting together in Enhancing Production of TMAO (Trimethylamine N-Oxide) may Increase Risk of Heart Attack

Food and gut microbes acting together in increasing production of TMAO (Trimethylamine N-Oxide) may increase the risk of Heart Attack from atherosclerosis.

Structure of Trimethylamine oxide (TMAO) (Photo credit: Wikipedia)

A study published online in the Cleveland Clinic on April, 2013 establishes the link between carnivorous/omnivorous food habit with predisposition to atherosclerosis and heart attack, to be TMAO (Trimethylamine Nitric-Oxide), a by-product of gut microbial action on certain foods containing lecithin and carnitine.

The researchers have proved that cholesterol cannot only be indicted to be the culprit in atherosclerosis, TMAO is the new found main facilitator for the plaque formation in the arterial walls.

Diets such as red meat and egg (Yolk) etc. when acted upon by the certain gut microbiota, produce TMAO, which is absorbed to the system and adversely affecting the reverse cholesterol transport; interferes with the metabolism of cholesterol in liver, only to facilitate its' deposition in the arterial walls, altering the macrophage foam cell function.

It is not precisely known which microbes from about a trillion of gut microbiota are responsible for increased TMAO production. In the study, when the gut flora was suppressed by antibiotics, production of this by-product was decreased. However, the Bacteroid type enterotype are associated with meat fat and protein eaters.

However, antibiotics are not recommended for prevention on heart attack because the gut flora recoups soon after the initial suppression by developing resistance.

The TMAO production was less in vegetarians and people on Mediterranean diet, in comparison to meat eaters. It is also interesting to observe that two different people can experience the same food differently because they have different gut flora. One person may generate a little more of a compound like TMAO than the other.

This concept is a new way of thinking about complex diseases like atherosclerosis and other cardiometabolic diseases. It can also apply to obesity and insulin resistance. Data links intestinal flora involvement in those phenotypes in both mice and humans.

There have been very exciting data from a gut flora transplant in persons with metabolic syndrome who received either their own fecal samples or those from a lean donor. Persistent changes in insulin sensitivity occurred just by transplanting the intestinal flora from one individual to another.

With the present level of knowledge, there has not been any recommendation on stopping meat eating for the purpose. But, promoting vegetarian diet is not a bad idea.

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• Few facts on probiotics and human gut flora
• Do These Microbes Make Me Look Fat?

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Antibiotic and PPI Associated Diarrhea

Endoscopic Image of Pseudomembranous Colitis Our gut harbors a number of bacteria; many of them protect us from colonization and harmful effect of deadly bacteria. In recent times pathogenic bacteria like C. difficile are more often found causing diarrhea; what is called pseudomembranous colitis a suferinfection.
This is most commonly seen following use of prolonged antibiotic therapy and use of proton pump inhibitors (PPI).
Commonly used antibiotics damage the normal gut flora and tilt the balance towards invasion and overgrowth of pathogenic bacteria. Prolonged PPI use decreases the acidic environment and allows multiplication of organisms harmful to body.
Clostridium difficile,  a bacterium that takes this opportunity to overgrow and causes diarrhea. It is also difficult to eradicate as is not susceptible to conventional antibiotics. A tough antibiotic called vancomycin is being used to treat it along with metronidazole. Some cases of vancomycin resistance have also been reported.
It is wise at the first place to prevent this superinfection by restricted use of antibiotics and supplementing with good bacteria during its use. Peudomembranous colitis can be treated by vancomycin, toxin‐binding medications, active vaccination, intravenous immunoglobin, and fecal bacteriotherapy (FB). Fecal bacteriotherapy is putting feces from healthy donors to the intestine of patient through colonoscopy.
Further, indiscriminate use of PPIs needs to stop making it available strictly on prescription.
In several interesting researches of recent times it has been seen that curcumin an active agent found in turmeric helps to improve gut health. It's likely that daily use of turmeric in hospital settings, in food products like curry or soup, can potentially decrease the incidence of Clostridium difficile associated diarrhea.
More studies are needed to determine the mechanism of action of turmeric and the physiological effects of turmeric in animal models of pseudomembranous colitis.
If this is ignored communities is likely to face situations like development of superbugs like (New Delhi Metallo) NDM-betalactamase1 and much more resistance strains of bacteria.

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• Attack on C. difficile: How can we combat this serious health issue (eurekalert.org)

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