Study shows how gut microbiota regulates weight loss & good fat in the cold.


A mammals’ body temperature is usually constant, however, when exposed to cold their body temperature drops by few degrees before slowly rising almost back to normal. This adaptive mechanism is mediated by the brown fat, whose function is to generate heat by burning calories once activated by cold. Therefore cold, as well as exercise, has the effect of favouring the appearance of adipose cells similar to brown fat, the beige fat, within white fat, which protects the body against excess weight and its damaging consequences.  Now, a study  from researchers at University of Geneva has shown that this beneficial health effect is mediated in part by gut microbes. The team state that their findings suggest that cold exposure dramatically alters the composition of intestinal bacteria in mice and that this microbial shift is sufficient to burn fat, improve glucose metabolism, and reduce body weight. The opensource study is published in the journal Cell.

Previous studies show that the gastrointestinal tract is the body’s largest endocrine organ that releases a number of regulatory peptide hormones that influence many physiological processes. At the apical surface, the epithelial cells have microvilli that further substantially increase the absorptive area and mediate the secretory functions. The intestinal microbiota co-develops with the host, and its composition is influenced by several physiological changes. A wide range of pathologies have been associated with alterations of the gut microbial composition. The intestinal microbiota can also influence the whole-body metabolism by affecting energy balance. The phenotypic and morphological changes that regulate the energy homeostasis of the new host following microbiota transplantation remain poorly understood.  The current study shows that the microbiota remodeling is an important contributor of the beige fat induction during cold and a key factor that promotes energy uptake by increasing the intestinal absorptive area, thus orchestrating the overall energy homeostasis during increased energy demand.

The current study exposed a group of mice to cold over a period of a month, dropping their environment temperature slowly from 20°C to 6°C to study how their microbiota changed.  Results show that mice exposed to cold experience a sharp shift in their microbiota composition, rendering them leaner and more sensitive to insulin. Data findings show that prolonged cold exposure can also attenuate the body weight loss as the body takes up more calories from the consumed food. The lab explained that this is due to a disappearance of a key bacterium, Akkermansia muciniphila, which acts on the way nutrients are absorbed by the organism; when the bacterium is artificially administered, weight loss resumes.

The researchers next tested the direct impact of these microbes on metabolic health. To do so, they transplanted the cold-induced gut bacteria into other mice that did not harbor gut microbes because they had been raised in a germ-free environment. Results show that the transplanted microbes improved glucose metabolism, increased tolerance to cold temperatures, and caused weight loss in the recipient mice by promoting the formation of beige fat.  The team state that these findings demonstrate that gut microbes directly regulate the energy balance in response to changes in the environment.  They go on to stress that after three weeks of cold exposure, body weight began to stabilize which they hypothesize is the intestine absorbing more nutrients from food, counteracting additional weight loss.

To validate this hypothesize the group performed transplantation experiments to show that gut microbes associated with long-term cold exposure caused the intestine to grow in size and triggered an increase in the surface area of intestinal cells that absorb nutrients.  The lab conclude that their findings demonstrate that gut microbes enable mammals to harvest more energy from food as a way to adapt to the increased energy demand associated with long periods of cold exposure, thereby helping to protect against hypothermia.

The team surmise that the gut is the largest endocrine tissue, which secretes many hormones acting in different parts of the human body; thus, altering the gut morphology might be one of the ways by which microbiota impacts all other organs, including the brain.  For the future, the researchers plan to study the molecular mechanisms by which gut microbes sense changes in the environment to affect the energy balance of the host. They go on to add that another avenue of investigation centers on the idea that certain bacteria may prevent obesity by remodeling intestinal tissue and thereby decreasing the absorption of nutrients in the gut.

Source: University of Geneva (UNIGE)

Microbial functions in the host physiology are a result of the microbiota-host co-evolution. We show that cold exposure leads to marked shift of the microbiota composition, referred to as cold microbiota. Transplantation of the cold microbiota to germ-free mice is sufficient to increase insulin sensitivity of the host and enable tolerance to cold partly by promoting the white fat browning, leading to increased energy expenditure and fat loss. During prolonged cold, however, the body weight loss is attenuated, caused by adaptive mechanisms maximizing caloric uptake and increasing intestinal, villi, and microvilli lengths. This increased absorptive surface is transferable with the cold microbiota, leading to altered intestinal gene expression promoting tissue remodeling and suppression of apoptosis—the effect diminished by co-transplanting the most cold-downregulated strain Akkermansia muciniphila during the cold microbiota transfer. Our results demonstrate the microbiota as a key factor orchestrating the overall energy homeostasis during increased demand.  Gut Microbiota Orchestrates Energy Homeostasis during Cold.  Trajkowski et al 2015.

Microbial functions in the host physiology are a result of the microbiota-host co-evolution. We show that cold exposure leads to marked shift of the microbiota composition, referred to as cold microbiota. Transplantation of the cold microbiota to germ-free mice is sufficient to increase insulin sensitivity of the host and enable tolerance to cold partly by promoting the white fat browning, leading to increased energy expenditure and fat loss. During prolonged cold, however, the body weight loss is attenuated, caused by adaptive mechanisms maximizing caloric uptake and increasing intestinal, villi, and microvilli lengths. This increased absorptive surface is transferable with the cold microbiota, leading to altered intestinal gene expression promoting tissue remodeling and suppression of apoptosis—the effect diminished by co-transplanting the most cold-downregulated strain Akkermansia muciniphila during the cold microbiota transfer. Our results demonstrate the microbiota as a key factor orchestrating the overall energy homeostasis during increased demand. Gut Microbiota Orchestrates Energy Homeostasis during Cold. Trajkowski et al 2015.

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