Gut microbiota mechanism

Hemarajata, P Versalovic, J., Effects of probiotics on gut microbiota Mechanisms of intestinal immu-nomodulation and neuromodulation. Therapeutic Advances in Gastroenterology (2013) 6, 39-51. 

Probiotic Microorganisms for Shaping the Human Gut Microbiota — Mechanisms and Efficacy into the Future... 

PROBIOTIC MICROORGANISMS FOR SHAPING THE HUMAN GUT MICROBIOTA - MECHANISMS AND EFFICACY INTO THE FUTURE... 

The gut microbiome is also being investigated for its role in severe malnutrition states such as kwashiorkor (156,157). Indeed, a complex interplay exists between the gut microbiota and host metabolism, and likely has far-ranging implications on normal metabolic homeostasis as well as several disease states, the mechanisms of which we are just beginning to elucidate. 

The final criterion for a prebiotic is that its fermentation in the colon has some beneficial impact on host health. In vitro studies using models of the colonic microbiota inoculated with human feces and studies in animals, have shown that fermentation of prebiotic fructans leads to accumulation of acetate and butyrate in intestinal/gut model contents. Fermentation of other prebiotics and certain dietary fibers has also been shown to increase propionate production in these systems. Small amounts of lactate and succinate can also be observed using in vitro models, but in vivo, these SCFA are rapidly converted into butyrate and propionate by the gut microbiota. Bifidobacteria and lactobacilli ferment carbohydrates mainly to acetate and lactate, but do not themselves produce butyrate. Recent studies have shown that dominant members of the Firmicutes, Eubacterium halli, Roseburia, Faecalibacterium prausnitzii and Anaerostipes caccae are able to cross-feed off acetate and lactate within the colonic milieu converting them into butyrate, providing a mechanism by which prebiotic modulation of acetate-produdng bifidobacteria can lead to elevated butyrate concentrations within the SCFA have been implicated... 

The mechanism of induction of low-grade chronic inflammation that accompanies HF-diet-induced obesity was demonstrated to be dependent on TLR-4. Interestingly, in the absence of TLR-4/CD14 receptor for LPS, no low-grade chronic inflammation and insulin resistance were induced by HF feeding in mice. Recently also TLR-2 and TLR-5 were shown to be involved in the innate immune system activation that is responsible for the inflammation induced after HF diet. These results confirm gut microbiota implication in the onset of metabolic disorders associated with obesity. Moreover, in animal studies at least, this high-fat-induced metabohc endotoxemia and subsequent metabolic disease may be reversed using prebiotic dietary fibers and certain bacterial supplements... 

Cani PD, Possemiers S, Van de Wiele T, et al. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut. 2009 58 1091—1103. 

To further clarify the causal role of gut microbiota in obesity, we need to answer two questions first, does the microbiota influence obesogenic pathways directly or through its components/metabolic products and second, are there specific host—microbe signaling mechanisms that lead to obesity ... 

In short, it is hard to conclude whether the gut microbiota is playing an active causative role in the development of obesity, or whether the obesity-associated profile of microbiota is simply in response to an obese state or the underlying diet. However, considering that the gut microbiota has been implicated in the onset of obesity in several animal studies, is modified by obesity and obesity-inducing diets, and appears to mediate some mechanisms of diet-related obesity and associated conditions, there is reasonable evidence to suggest its importance in metabolic health. The "chicken and egg" question therefore seems inconsequential compared to the significance of elucidating the role of the gut microbiota in host nutritional metabolism. 

---