How Gut Bacteria are Involved in Obesity

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Christoph Thaiss has been named the 2018 Grand Prize winner of the Science & SciLifeLab Prize for Young Scientists for work that implicates the microbiome as a common culprit underlying hallmarks associated with human obesity, a complex and multifaceted disease.

Thaiss and his team discovered that specific molecules produced by intestinal bacteria are altered during three specific instances that have each been associated with human obesity: the disruption of the biological clock, recurrent weight gain and enhanced susceptibility to infection.

The molecular processes involved in metabolic disease are poorly understood, in part because both genetic and environmental factors contribute to its onset. “The metabolic effects of obesity are also largely variable in different individuals and influence multiple different organ systems, and as such, the study of obesity and the development of new therapeutic strategies require integration of technologies from many different scientific disciplines,” said Thaiss.

The prize, now in its sixth year, recognizes promising early-career scientists who conduct groundbreaking life-science research and includes a grand-prize award of US $30,000. It is supported by SciLifeLab (Science for Life Laboratory), a national center for advanced molecular life sciences in Sweden and the journal Science, which is published by AAAS, the nonprofit science society. The prize is also made possible through the kind support of the Knut and Alice Wallenberg Foundation, which promotes scientific research, teaching and education. The foundation is the largest private financier of research in Sweden.

“The human lifestyle has dramatically changed over the last century, and so has our susceptibility to various metabolic diseases,” said Thaiss. In his grand-prize winning essay, “Microbiome dynamics in obesity,” which will appear in the November 23 issue of Science, Thaiss’ findings suggest that elements of the modern human lifestyle like the disruption of the biological or circadian clock by shift work or erratic weight management by cycles of diets may impact metabolic health through their effect on the intestinal microbiome.

“A deeper understanding of the factors controlling the activity of the microbiome will enable us to understand the specific mechanisms underlying environmental impacts on human disease, and may provide us with actionable predictions of how certain lifestyle changes can have preventive or therapeutic effects,” said Thaiss.

Previous research has linked clock disturbances to obesity and high blood sugar, and Thaiss discovered that the gut microbiome in both mice and humans undergoes fluctuations in a 24-hour rhythm. He then showed that such daily oscillations in the intestinal microbial community influence the circadian biology of the host. Interestingly, Thaiss observed that disruption of host circadian rhythms either genetically or by jet lag altered the intestinal microbiome, which predisposed the rodents and humans to obesity and glucose intolerance.

Thaiss also studied microbiome disruption on longer time scales, as the rapid weight regain of formerly obese individuals after successful weight loss – a phenomenon commonly known as the “yo-yo effect” – continues to puzzle scientists. In mice, Thaiss found that a period of obesity induced long-lasting alterations in microbiome composition that persisted even after the host organism returned to normal weight – “memory-like” behavior that predisposed formerly obese animals to experience accelerated weight regain.

Thaiss lastly addressed the enhanced susceptibility of obese and diabetic individuals to intestinal infection and systemic inflammation. Intestinal epithelial cells, which line the intestinal tract normally provide a tight barrier that separates intestinal bacteria from the circulatory system. His analysis of obese and diabetic mice revealed that breakdowns in the intestinal epithelial barrier led to the transport of bacterial molecules to the blood stream, which caused inflammation. Importantly, Thaiss validated these results in a human cohort, where chronic high blood sugar strongly correlated with the levels of microbial products detected in the circulation.

“Since most of our work was carried out using mice to model obesity and its metabolic complications, the most important next step will be to translate our findings to human obesity. Our first insights indicate that the fundamental mechanisms we discovered can be applied to human biology. Whether our approach can be used to improve metabolic health in humans is an exciting question that we are actively pursuing,” said Thaiss.

“Understanding the interplay between diseases like obesity and the bacteria that live in our gut may suggest new approaches for therapeutic intervention,” said Valda Vinson, deputy editor of Science.

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