Gut's microbial community shown to influence host gene expression

Gut's microbial community shown to influence host gene expression

In our guts, and in the guts of all animals, resides a robust ecosystem of microbes known as the microbiome. Consisting of trillions of organisms -- bacteria, fungi and viruses -- the microbiome is essential for host health, providing important services ranging from nutrient processing to immune system development and maintenance.

Now, in a study comparing mice raised in a "germ free" environment and mice raised under more typical lab conditions, scientists have identified yet another key role of the microbes that live within us: mediator of host gene expression through the epigenome, the chemical information that regulates which genes in cells are active.

Writing in the journal Molecular Cell, a team of researchers from the University of Wisconsin-Madison describes new research helping tease out the mechanics of how the gut microbiome communicates with the cells of its host to switch genes on and off. The upshot of the study, another indictment of the so-called Western diet (high in saturated fats, sugar and red meat), reveals how the metabolites produced by the bacteria in the stomach chemically communicate with cells, including cells far beyond the colon, to dictate gene expression and health in its host.

The study revealed key differences in gene regulation in conventionally raised mice and mice raised in a germ-free environment. The mice were provided with two distinct diets: one rich in plant carbohydrates similar to fruits and vegetables humans consume; the other mimicking a Western diet, high in simple sugars and fat.

The new study shows that a small set of short-chain fatty acids produced as the gut bacteria consume, metabolize and ferment nutrients from plants are important chemical messengers, communicating with the cells of the host through the epigenome.

In the study, the gut microbiota of the animals that were fed a diet rich in sugar and fat have a diminished capacity to communicate with host cells. According to the team, that may be a hint that the template for a healthy human microbiome was set in the distant past, when food from plants made up a larger portion of diet and sugar and fat were less available than in contemporary diets with more meat and processed foods.

Foods rich in fat and sugar, especially processed foods, are more easily digested by the host, but are not necessarily a good source of food for the flora inhabiting the gut. The result is a less diverse microbiome and less communication to the host, according to the researchers.

A surprising finding in the study is that the chemical communication between the microbiome and host cells is far reaching. In addition to talking to cells in the colon, the microbiome also seems to be communicating with cells in the liver and in fatty tissue far removed from the gut.

The kicker experiment in the study, was providing mice raised in a germ-free environment with three different short-chain fatty acids that the study showed to be important messengers to the epigenome. The supplement was enough to promote the kind of healthy interplay between microbiota and host cells seen in mice given a diet high in plant fiber.