The existing evidence about a different gut microbiota composition between healthy and obese or type 2 diabetic patients has led scientists to study the role of gut microbes in the onset and development of metabolic diseases. Several mechanisms by which the gut microbiota may interfere with energy metabolism are currently being explored, though it is not fully understood how the gut microbiome affects energy expenditure in the host.

A new study, led by Dr. John Speakman from the State Key Laboratory of Molecular Developmental Biology at the Chinese Academy of Sciences in Beijing (China), has found that the gut microbiota affects thermogenesis in brown and beige adipocytes in mice.

The authors sought to explore the impact of gut microbiota on brown adipose tissue (BAT) and white adipose tissue (WAT) beiging, as both are potential targets for therapy for obesity and related metabolic conditions.

Under a cold temperature (4ºC), different antibiotic cocktails led to decreased gene expression and protein levels of uncoupling protein 1 (UCP1)—involved in reducing ATP synthesis and generating heat in the mitochondrial respiratory chain—in both BAT and subcutaneous WAT. Antibiotic mice also exhibited temporary weight loss due to decreased energy absorption capacity, which was not, however, responsible for the observed dampened thermogenic capacity.

In contrast, gut microbiota depletion through antibiotics did not affect the thermogenic capacity of neither BAT nor WAT at 22ºC, compared to control colonized mice.

The researchers also went a step further and explored if these findings were not down to the toxic effects of antibiotics on UCP in mitochondria. However, this was not the case, given that daily energy expenditure and UCP1-dependent thermogenesis were also blunted in germ-free mice treated with the highly selective beta 3-adrenergic receptor agonist CL-316243 (a selective activator of brown and beige adipocytes).

In short, by using two different models for studying the contribution of the gut microbiota in adaptive thermogenesis, Dr. Speakman and colleagues found that the depletion of gut microbiota can decrease UCP1 expression and whole-body energy expenditure. As a result, the absence of the gut microbiota impaired both the browning of WAT and capacity for UCP1-dependent thermogenesis.

Indirect calorimetry also showed that antibiotic impairment of BAT and subcutaneous WAT thermogenesis also led to a fall in whole-body energy expenditure at room and cold temperatures.

Meanwhile, the repopulation of gut microbiota and the gavage of butyrate in antibiotic-treated mice led to a partial reverse in the thermogenic capacity of BAT and WAT browning. Isotope tracing also revealed that butyrate was preferably uptaken in the brain rather than in BAT and WAT.

The role of butyrate in enhancing host energy expenditure and promoting UCP1 expression offers a promising area of research for further study.

To sum up, these findings in mice support the contribution of gut microbiota to the body’s heat generation in response to cold temperatures in mice. For the first time, this study has clarified the effects of gut microbiota on different adipocytes. Whether the gut microbiota and butyrate may affect host metabolic homeostasis, thus regulating food intake through thermogenesis, is, however, not known and therefore deserves further research.



Li B, Li L, Lam SM, et al. Microbiota depletion impairs thermogenesis of Brown adipose tissue and browning of white adipose tissue. Cell Rep. 2019; 26(10):2720-37. doi: 10.1016/j.celrep.2019.02.015.