Bhanu P. Ganesh

Role of the Gut Microbiome in Obstructive Sleep Apnea-Induced Hypertension.

Individuals suffering from obstructive sleep apnea (OSA) are at increased risk for systemic hypertension. The importance of a healthy gut microbiota, and detriment of a dysbiotic microbiota, on host physiology is becoming increasingly evident. We tested the hypothesis that gut dysbiosis contributes to hypertension observed with OSA. OSA was modeled in rats by inflating a tracheal balloon during the sleep cycle (10-s inflations, 60 per hour). On normal chow diet, OSA had no effect on blood pressure; however, in rats fed a high-fat diet, blood pressure increased 24 and 29 mm Hg after 7 and 14 days of OSA, respectively (P<0.05 each). Bacterial community characterization was performed on fecal pellets isolated before and after 14 days of OSA in chow and high-fat fed rats. High-fat diet and OSA led to significant alterations of the gut microbiota, including decreases in bacterial taxa known to produce the short chain fatty acid butyrate (P<0.05). Finally, transplant of dysbiotic cecal contents from hypertensive OSA rats on high-fat diet into OSA recipient rats on normal chow diet (shown to be normotensive) resulted in hypertension similar to that of the donor (increased 14 and 32 mm Hg after 7 and 14 days of OSA, respectively; P<0.05). These studies demonstrate a causal relationship between gut dysbiosis and hypertension, and suggest that manipulation of the microbiota may be a viable treatment for OSA-induced, and possibly other forms of, hypertension.

Luminal Conversion and Immunoregulation by Probiotics

Beneficial microbes are responsible for the synthesis of nutrients and metabolites that are likely important for the maintenance of mammalian health. Many nutrients and metabolites derived from the gut microbiota by luminal conversion have been implicated in the development, homeostasis and function of innate and adaptive immunity. These factors clearly suggest that intestinal microbiota may influence host immunity via microbial metabolite-dependent mechanisms. We describe how intestinal microbes including probiotics generate microbial metabolites that modulate mucosal and systemic immunity.

Microbial Interactions with the Intestinal Epithelium and Beyond: Focusing on Immune Cell Maturation and Homeostasis

Purpose of ReviewOur perception of human microbes has changed greatly in the past decade from a focus on pathogens and infections to a new world view of mutualism and coevolution of microbes and mammalian hosts. This review article seeks to explain the dynamic interactions occurring between the intestinal microbiome and the mammalian host mucosa..Recent FindingsMicrobial metabolites influence the functions of epithelial, endothelial, and immune cells in the intestinal mucosa. Microbial metabolites like SCFAs and B complex vitamins influence macrophage differentiation and polarization, whereas microbe-derived biogenic amines such as histamine modulate the biology of the intestinal epithelium and immune responses. Aberrant bacterial lipopolysaccharide-mediated signaling may be involved in the pathogenesis of chronic intestinal inflammation and colorectal carcinogenesis.SummaryWe conclude that gut microbes (commensals and probiotics) can have profound impact on mammals by modulation of intestinal immunity and physiology and by influencing the functions of various cell types within the intestine. In addition, microbial metabolites have well-defined effects on shaping the gut epithelium, and these compounds play a key role in maintaining intestinal homeostasis. Therefore, effectively manipulating the microbiome via changes in diet and microbial composition and function may yield advances regarding diagnosis and treatment.