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How the intestinal microbiome influences metabolism

New research from the Boston Children’s Hospital, which draws upon the rich stream of data emanating from human microbiome research, shows how the human body’s innate immune system, which is the first line of defense against bacterial infection, has an additional function. This function appears inextricably linked to health and well-being through the fine-tuning the body’s metabolism.

This research, however, has not been conducted directly on people and the findings are applied. For the latest research the fruit fly has been used as the study tool. Drosophila has useful attributes that have fueled its widespread use in biological research; the flies also have a short generation cycle (10 days) and life span, plus flies and humans have common evolutionary roots and display striking similarities at the level of their genes, cells, tissues and the biological processes.

While it has long been established that in the intestine the body’s digestive cells use an innate immune pathway to respond to pathogenic bacteria, less has been known about the functions of other intestinal cells like enteroendocrine cells. These cells have been shown to use the same pathway to respond to beneficial bacteria.

The new research shows how these cells can fine-tuning body metabolism to diet and intestinal conditions as an adaptive response. This was through bacteria living in flies’ intestines being shown to make a short-chain fatty acid called acetate, and this microbial metabolic signal activates signaling through the enteroendocrine pathway.

This fatty-acid is necessary for the flies’ own lipid metabolism and insulin signaling. Moreover, flies without any bacteria in their intestines accumulated fat droplets in their digestive cells; something that causes ill health. Further study showed that fat droplets caused by a reduction in beneficial intestinal bacteria, would probably lead to the equivalent of fatty liver in people, and thus an association with obesity and type 1 diabetes.

The research next needs to be run in a mammalian model to determine if the findings can be replicated. If so it indicates the importance of the balance of bacteria that form the basis of the gut microbiome, the collection of microorganisms and their genetic interactions.

The research is published in the journal Cell Metabolism, with the study paper titled “The Drosophila Immune Deficiency Pathway Modulates Enteroendocrine Function and Host Metabolism.”

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Dr. Tim Sandle is Digital Journal's Editor-at-Large for science news. Tim specializes in science, technology, environmental, business, and health journalism. He is additionally a practising microbiologist; and an author. He is also interested in history, politics and current affairs.

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