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.