International Business Department           Liu Bojia           September 6, 2023

  Some people work hard to exercise and control their appetites in order to curb their soaring weight, while others are slim despite their frequent consumption of fried chicken and barbecue meat. While this difference is greatly contributed by our own genetics, it is also inextricably linked to the gut flora of different people.

  Countless microorganisms in the gut influence our digestion, absorption and metabolic storage of nutrients. Scientists have long recognized that the composition of gut flora differs significantly between obese and lean people. In the lab, researchers have observed the same trend in mice: fat mice have different gut flora than lean mice.

  Interestingly, the mouse experiments also showed a puzzling phenomenon: if there was a complete absence of gut flora and always lived in a sterile environment, such mice tended to be thinner than their counterparts with intact intestinal flora, and even when they were fed high-sugar and high-fat foods, they did not gain weight.

  Eating greasy but not gaining weight is not to be envied by many in a world where obesity is becoming an increasingly common problem. Scientists are also hoping to take a cue from this to find a solution to the obesity problem, especially in preventing and treating diet-induced obesity.

  A recent research paper published in the leading academic journal Science has identified a key molecule that regulates lipid absorption and diet-induced obesity through this clue. At the same time, the researchers suggest that, based on the new findings, it is possible to go in the opposite direction and develop treatments for malnutrition, providing help to others who struggle to "eat fat".

  In this study, a team led by Professor Lora Hooper of the University of Texas Southwestern Medical Center and Dr. Yuhao Wang (now at Zhejiang University) first conducted an experiment to examine gene expression in the epithelial cells of the small intestine of germ-free mice through RNA sequencing.

  After comparing them to regular mice with intact intestinal flora, the researchers noticed that several genes encoding long non-coding RNAs (lncRNAs) were expressed in significantly different amounts in the intestinal cells of germy and germ-free mice.

  The authors focused on one of these genes, Snhg9, and found that the RNA molecule produced by this gene acted as a "grease scraper," limiting the absorption of fat from food in the small intestine.

  Specifically, in the small intestinal epithelial cells of germ-free mice, a high concentration of Snhg9 product interacts with and binds to a protein called CCAR2, which in turn contributes to the latter's inhibition of sirtuin, a regulatory factor in lipid metabolism. This series of molecular cascade reactions ultimately prevented the efficient absorption of lipids by intestinal cells, resulting in a high-sugar, high-fat diet that also made it difficult to fatten these mice.

  In contrast, mice with intact gut flora were easily fattened by the high-sugar, high-fat diet, associated with lower levels of lncRNA molecules such as Snhg9 in their bodies. Experiments showed that this was due to lymphocytes in the immune system signaling the "presence of bacteria," prompting the small intestinal epithelial cells to reduce Snhg9 expression.

  When the researchers genetically modified the small intestinal epithelial cells to produce more Snhg9 RNA molecules, they were saved from eating fat. And when, again by means of genetic modification, the mice were in turn made deficient in Snhg9 RNA, then even after the gut flora was killed with antibiotics, these mice gained extra weight as a result of enjoying a high-fat diet.

  Taking these findings together, the researchers propose that both over- and undernourished people can be brought back to health by manipulating this interaction. On the one hand, by pharmacologically mimicking the function of Snhg9, it is expected to prevent and treat obesity and obesity-associated diabetes and other metabolic disorders; on the other hand, by inhibiting Snhg9, it is expected to treat malnutrition and enhance the absorption of nutrients.