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Gut bacteria, our health and what we can do (part 2)

#Tejasvani knowledge desk

We consider the basic requirement of good gut health consists in.

1.     Gut bacteria in right scale, right proportion and in right places.

2.     Insulin sensitivity

3.     Anti-inflammatory environment

4.     Healthy mucosal immune system in intestines, and

5.     Polyphenols as enabling agent for prebiotic and its anti-microbial property against pathogenic gut microbe. In addition to modulating gut metabolism and immunity and displaying anti-inflammatory effects.


Of this first one is the most difficult part.


The human GI tract functions to digest foods and uptake nutrients. It also protects from pathogen infection as well as maintains immune tolerance. Undigested foods reach the colon and serve as substrates for bacterial metabolism. Carbohydrates, proteins, and fats are the three major macronutrients that serve as an energy source in human nutrition; they differ greatly in digestibility and, therefore, provide quite different microbiota-accessible nutrients. The amount and types of macronutrients select the growth of different bacteria and generate different metabolites, which have positive or negative effects on the gut epithelium and mucosal immune system. Indigestible carbohydrates are a major type of dietary fiber and select fiber-degrading bacteria, which produce short-chain fatty acids (SCFAs). SCFAs, in general, are considered to be beneficial to gut health under normal conditions. Undigested proteins in the range of 10–30% promote the growth of proteolytic bacteria, which produce SCFAs, branched-chain fatty acids, and some toxic metabolites, including ammonia and hydrogen sulfides. Bile acids are secreted in response to dietary fats and form conjugated fatty acids. About 5% of conjugated fatty acids reach the colon for bacterial metabolism. Dietary fats select bile acid-tolerant bacteria, which produce toxic compounds like H2S.


The gut microbiome, or gut microbiota, also termed commensal, refers to the entire microbial community that populates the mammalian gastrointestinal (GI) tract, with the majority residing in the colon. The human gut microbiome reaches 3.8 × 1013 microbes in a standard adult male, which outnumbers the human host cells (3.0 × 1013). Each individual hosts at least 160 species out of the total 1150 species that colonize the human GI tract. There are five major phyla for the human gut microbiota,

namely FirmicutesBacteroidetesActinobacteriaProteobacteria, and Verrucomicrobe, with the two dominating phyla, Firmicutes and Bacteroidetes, representing 90% of the gut microbiota. Some bacteria termed “pathobionts” can become pathogenic under specific conditions. For example, members of the phylum Proteobacteria belong to “pathobionts”, and a bloom of them is seen in inflammatory bowel disease (IBD). Accumulating evidence has shown that a diversified and well-structured gut microbiota is critical in maintaining health. Dysbiosis, defined as reduced diversity and alterations of the composition of the gut microbiota, is associated with obesity, diabetes, and gastrointestinal diseases such as IBD. Diet is a driving factor in shaping human gut microbiota composition and function. There is growing interest in targeting the gut microbiota through diet and nutritional approaches either to promote gut health or as an adjunct therapy for treating IBD.


Compared with human metabolism, bacterial metabolism is much more powerful considering the fact that the gut microbial genes (3.3 × 106) far outnumber human protein-coded genes by 150-fold .What is more, bacterial metabolism can switch from one substrate to another substrate much faster, depending on substrate availability. A healthy gut microbiome is characterized by a diversified bacterial community, where different species are equipped with different catabolism capacities and work in concert.


Through generating a diverse array of metabolites, the gut microbiome interacts with the gut epithelium and the intestinal mucosal immune system to maintain gut homeostasis, thus forming a symbiotic relationship with the host. Diet can disturb gut homeostasis by influencing the diversity, composition, and function of the gut microbiome. A nutritionally balanced diet is critical for maintaining a healthy gut microbiome, the integrity of the intestinal barrier, immune tolerance, and normal gut physiology, whereas an unbalanced diet, like the typical western diet, results in reduced diversity and dysbiosis of the gut microbiome, which can lead to a leaky gut and chronic inflammation, as seen in IBD. 

 

Diet, the Microbiome, and the Intestinal Barrier

The human GI tract is covered by a single layer of epithelial cells held together by tight junction proteins The intestinal epithelial cells form a physical barrier as they are impermeable to luminal contents. There are at least seven types of intestinal epithelial cells: enterocytes, goblet cells, Paneth cells, microfold cells, enteroendocrine cells, cup cells, and tuft cells. Enterocytes are the most abundant cells responsible for nutrient uptake. Goblet cells, with more abundance in the distal direction, are responsible for producing mucus. Most Paneth cells reside in the small intestine and secret antimicrobial peptides. The intestinal epithelial cells and the secreted factors form the intestinal barrier.


The glycoprotein-rich mucus layer overlying the gut epithelium is the first line of defense against commensal microbes as well as pathogens. The large intestine has two layers of mucus, namely, a firmly attached bacteria-free inner layer and a loose outer layer. The inner layer is about 200–300 μm thick in humans. The outer layer expands 4–5 times in volume, which creates a habitat for the commensal bacteria. The mucus barrier is also a reservoir of antimicrobial peptides and IgA. The inner mucus layer is continuously renewed every 1–2 h in murine colonic tissue. Once the inner mucus layer is lost or becomes penetrable to bacteria, a large number of bacteria will reach the epithelial cells and trigger inflammation. Thus, a penetrable inner mucus layer allowing large quantities of bacteria to reach the epithelial cells is a common mechanism for all mouse models of colitis and patients with active ulcerative colitis.


The permeability of the intestinal barrier is tightly regulated in a healthy gut. The commensal bacteria maintain the epithelial barrier by providing energy in the form of short-chain fatty acids and also releasing antimicrobial substances to inhibit pathogens. Some nutrients are important regulators of tight junction protein levels, which are critical in maintaining the epithelial barrier. An increase in intestinal permeability, termed a “leaky” gut, can be induced by dietary factors and may trigger inflammatory responses. In a healthy gut, a balance exists between commensal bacteria and the mucus layer. Some gut bacteria, termed mucin specialists, specifically metabolize mucins and are the major mucin degraders when the diet is rich in dietary polysaccharides. There is a balance of production and degradation of mucus, which maintains the thickness of the mucus layer. Dietary fiber-derived SCFAs promote the integrity of intestinal epithelium by inducing goblet cells to increase mucin production and enterocytes to secret IL-18, which is important for epithelial repair. SCFAs can also directly modify tight junctions to strengthen the gut barrier. When the diet is devoid of dietary fibers, some mucin generalists switch metabolism from plant polysaccharides to host mucin glycans. Expansion of mucus-degrading bacteria and an increase in the metabolic activity in utilizing mucin glycans lead to erosion of the mucus layer. Reduced dietary fiber correlates with the thinning of colonic mucus. Different protein sources also affect the thickness of the mucus layer. High saturated fats impair intestinal barrier integrity by reducing tight junction protein occludin and ZO-1. Simple sugars and emulsifiers negatively affect the intestinal barrier by inducing the expansion of mucin lytic bacteria such as Akkermansia muciniphila, which leads to a thinning of the mucus layer.

 



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