Gut Microbiota: From Fundamental Research to Translational Medicine

Abstract

The human microbiota is a hot topic at present because increasing evidences demonstrate that it should be considered an organ based on its importance to human health . Dysbiosis of the gut microbiota is significantly related to many human disorders. In turn, correcting such imbalances and taking advantage of gut microbes are possible methods for alleviating or even curing host diseases. A recent study published in Cell indicated that inhibition of gut microbial production of trimethylamine(TMA) specifically prevents atherosclerosis in vivo. Another study found that a diet supplemented with TMA Noxide (TMAO) increased the level of atherosclerosis in mice , which suggested TMAO might be a causative factor in cardiovascular disease (CVD). However, direct inhibition of flavin-containing monooxygenase (FMO3), a hepatic enzyme that catalyzes the conversion of TMA to TMAO, results in TMA accumulation and several unpleasant side effects. The small-molecule 3,3-dimethyl-1-butanol (DMB), identified by Wang et al., reduces TMAO through non-lethal inhibition of microbial TMA formation in mice, even when fed a western diet, including high choline. DMB is a non-toxic compound found naturally in foods such as olive oil and red wine. Therefore, the risk of CVD could be reduced by some dietary habits (such as a Mediterranean diet), which might stem from changes in gut microbiota. Although the impact of DMB on microbial TMA has only been observed in mouse models, it provides a guideline for the treatment of CVD in humans by regulating gut microbes. There are many similar studies that target gut microbes to treat host disorders. For example, Sarkis’ group verified that a human commensal bacterium could improve autism spectrum disorder (ASD)-related gastrointestinal deficits and behavioral abnormalities in mice , which indicated that microbiome-mediated therapies might be a safe and effective treatment for ASD. In addition, fecal microbiota transplantation, which has aroused strong interest in recent years, is reported to be a highly successful therapy for recurrent Clostridium difficile infection . These studies support novel research ideas that are no longer focused solely on the host, but rather on the intimacy of the host-microbiota relationship. Considering the relative ease of regulating the gut microbiota, targeting these organisms through diet, prebiotics, probiotics, or other methods may become a useful strategy for curing diseases. To date, a large number of studies have been devoted to uncovering the relationship between microbial metabolites and human diseases, and it is highly likely that more bacterial or related pathways involved in human disease will be identified. In the future, targeting the microbiome may represent an effective and complementary strategy to current approaches for preventing and treating diseases.