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The complexities of host-microbiota interaction
▸ Faith JJ, Ahern PP, Ridaura VK, et al. Identifying gut microbe-host phenotype relationships using combinatorial communities in gnotobiotic mice. Sci Trans Med 2014;6:220ra11.
Identifying which members of the colonic microbiota actively participate in processes that affect physiology, metabolism, immunity and disease progression is challenging. Gut commensal bacteria and metabolites they produce, including short chain fatty acids, have been shown to regulate colonic regulatory T (Treg) cells in mice. These cells express the transcription factor Foxp3, secrete interleukin 10 and are critical in controlling intestinal inflammation by limiting proliferation of effector CD4 T cells. This highlights the complex effects of inflammation on microbial composition/activity and the host's ability to protect itself from a dysbiotic microbiota. This work has further demonstrated how colonic bacteria shape the immune landscape, and shows that the consortium of bacteria capable of shaping the Treg response spans different bacterial phyla, suggesting a common pathway by which bacteria can influence the host immune response. The authors transplanted intact uncultured microbiota from human donors into germ-free mice, to identify features of the donors that are transmissible. They then clonally arrayed bacteria from donors and sequenced/identified the strains whose presence or absence best explained phenotypical variation. Through this approach they identified a wide range of bacteria that influenced expansion and accumulation of various Treg cell subsets. They also identified bacterial strains that modulated adiposity and caecal metabolite concentrations. Identifying these effector strains represents the first stage in delineating the implications of how the gut microbiota impacts on the host. Also, the system described could be used to screen next-generation probiotics and synbiotics to more fully understand their impact on host biology.
FGF21 in obesity related metabolic disorders
▸ Emanuelli B, Vienberg SG, Smyth G, et al. Interplay between FGF21 and insulin action in the liver regulates metabolism. J Clin Invest 2014;124:515–27.
Worldwide, obesity related …
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