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Slimming, the gut bug way

It seems there is more to the saying “You are what you eat”. A growing body of evidence suggests that the size and shape of your body is determined not just by what you eat but also by zillions of bugs residing inside your body.

Now a new study — by a US research team that includes a scientist of Indian descent — has shown that gut immunity plays a role in deciding whether one has the propensity to gain weight if given a high-fat diet.

The finding is significant because it indicates that it would be possible to make a person gain or lose weight by simply altering the microbes in the gut, using probiotics or antibiotics. Collectively called microbiome, the human gut harbours over 100 trillion (million times million) bacteria. These bugs, which belong to nearly three million types, account for nine out of 10 cells in the human body.

The immune system plays a role in coordinating changes in the gut microbial community that appears to promote weight gain, says Vaibhav Upadhyay, a research student at the University of Chicago who is the first author of the paper that appeared online in Nature Immunology yesterday.

“This understanding offers an exciting theoretical possibility of regulating weight gain by manipulating one’s immune system,” Upadhyay, whose parents hail from Madhya Pradesh, told KnowHow.

Upadhyay, a second-generation non-resident Indian, grew up in Rockford in Illinois and has been studying the role of a protein called lymphotoxin in modulating micobiota in the gut under the guidance of Yang-Xin Fu, the senior author of the study.

Their studies in mice have shown that when the genes responsible for the production of lymphotoxin are knocked off, the animals do not gain weight despite being fed a high-fat diet. Lymphotoxin belongs to a super family of proteins that play an important role in triggering a wide variety of immune responses. Its primary role is to regulate the formation of lymph nodes that trap foreign particles before they are destroyed by the immune system.

The Chicago University scientists have shown that lymphotoxin has another role too — that of protecting the gut from harmful microbes by regulating the production of anti-microbial compounds, which are quite similar to antibiotics. It is this beneficial activity of lymphotoxin that leads to weight gain if on a high-calorie diet, says Upadhyay.

Now that they know that lymphotoxin plays a critical role in promoting weight gain, the next step is to understand how the body uses the lymphotoxin signalling system to promote weight gain. “We are also interested in using lymphotoxin to figure out which microbes are important in weight gain and attempting a therapeutic intervention in mice based on that data,” Upadhyay says.

Closer home, researchers from Pune have found in another study that there are subtle differences in the composition of gut bacteria in people with normal body structure and those who are obese. “While a majority of the microbes are the same in both thin and obese people, certain types of bacteria are more abundant in obese people,” says Yogesh Shouche of the National Centre for Cell Science (NCCS) in Pune, who led the study.

The subjects they studied included people who have undergone weight reduction surgeries such as bariatric surgery. Significantly, the scientists found that in such people the type of bacteria found in obese people hadn’t come down to the level found in normal people.

“We are curious to know whether such bacteria have anything to do with promoting obesity,” Shouche told KnowHow. The study, scheduled to appear in the September issue of Journal of Biosciences, is just a preliminary one, he says.

The team, which includes scientists from Agarkar Research Institute and Rubi Hall Clinic, apart from NCCS, is planning to embark on a larger study involving larger joint families from villages around Pune. “Doing such studies in joint families where three to four generations of people live has several advantages,” observes Shouche. “With all of them eating the same food, drinking the same water and being exposed to more or less similar conditions, their environmental conditions remain the same. So genetic factors can be easily separated out.”

“We still have very little understanding of how much the gut microbiota contribute to metabolism. Understanding this will be really beneficial in tackling many lifestyle diseases that are caused by metabolic abnormalities,” says the NCCS researcher.

Well, it’s always smart to trust your gut feeling.

 
 
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