Mechanistic links between gut microbial community dynamics, microbial functions and metabolic health

Abstract

Gut microbes comprise a high density, biologically active community that lies at the interface of an animal with its nutritional environment. Consequently their activity profoundly influences many aspects of the physiology and metabolism of the host animal. A range of microbial structural components and metabolites directly interact with host intestinal cells and tissues to influence nutrient uptake and epithelial health. Endocrine, neuronal and lymphoid cells in the gut also integrate signals from these microbial factors to influence systemic responses. Dysregulation of these host-microbe interactions is now recognised as a major risk factor in the development of metabolic dysfunction. This is a two-way process and understanding the factors that tip host-microbiome homeostasis over to dysbiosis requires greater appreciation of the host feedbacks that contribute to regulation of microbial community composition. To date, numerous studies have employed taxonomic profiling approaches to explore the links between microbial composition and host outcomes (especially obesity and its comorbidities), but inconsistent host-microbe associations have been reported. Available data indicates multiple factors have contributed to discrepancies between studies. These include the high level of functional redundancy in host-microbiome interactions combined with individual variation in microbiome composition; differences in study design, diet composition and host system between studies; and inherent limitations to the resolution of rRNA-based community profiling. Accounting for these factors allows for recognition of the common microbial and host factors driving community composition and development of dysbiosis on high fat diets. New therapeutic intervention options are now emerging.

Nutrient-Gene Interaction in Colon Cancer, from the Membrane to Cellular Physiology

“…Some protective metabolites produced by the microbiota include short-chain fatty acids, such as acetate, butyrate, and propionate. A range of gut microbial structural components and metabolites directly interacts with host intestinal cells and stroma to influence nutrient uptake and epithelial resilience (75). For example, we and others have proposed that n-3 PUFA and butyrate, a four-carbon short-chain fatty acid produced during anaerobic fermentation of dietary fiber by endogenous bacteria in the colon, interact to profoundly suppress colon cancer (30, 110, 111).…”

Intestinal bacteria are necessary for doxorubicin-induced intestinal damage but not for doxorubicin-induced apoptosis

“…3 The gastrointestinal tract is home to a vast population of commensal bacteria and numerous studies have demonstrated the importance of the symbiotic relationship between intestinal bacteria and IECs in maintaining homeostatic functions of the intestine, including nutrient generation and metabolism and proper development of the innate immune system. [4][5][6][7] Evidence in models of intestinal damage, indicate distinct effects of bacteria in different regions of the gastrointestinal tract. For example, in colon of mice that lack TLR signaling (MyD88¡/¡), restitution and repair following epithelial injury is impaired.…”

Microbiota, Immune System and Colorectal Cancer

“…Заселение кишечника таких мышей микробиотой обес-печивало восстановление мукозальной иммунной сис-темы и индуцирование экспрессии различных генов, связанных с поглощением нутриентов, метаболизмом, ангиогенезом, мукозальной барьерной функцией и раз-витием нервной системы кишечника. Микробиота в кишечнике контактирует со 2-м (после мозга) наибо-лее крупным пулом нервных клеток организма и с са-мым крупным пулом иммунных клеток, оказывая влияние на формирование когнитивных функций и им-мунный статус организма [5][6][7].…”