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John Hopkins Study Ties Gut Bacteria to Obesity

John Hopkins Study Ties Gut Bacteria to Obesity
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By    |   Monday, 12 February 2018 12:13 PM

Researchers at Johns Hopkins have conducted a study that found that the intestinal microbe — the bacterial, viral, and fungal genes that make up the gut's biome — plays a significant role in the development of obesity and insulin resistance in mammals, including humans.

The study, which studied mice with the rodent equivalent of metabolic syndrome, emphasized the potential to prevent obesity and diabetes by controlling the levels of gut bacteria, and/or modifying the actions of genes that control metabolism.

"This study adds to our understanding of how bacteria may cause obesity, and we found particular types of bacteria in mice that were strongly linked to metabolic syndrome," says the study's senior author Dr. David Hackam, surgeon-in-chief and co-director of Johns Hopkins Children's Center.

"With this new knowledge we can look for ways to control the responsible bacteria or related genes and hopefully prevent obesity in children and adults," he continued.

Metabolic syndrome is a cluster of conditions including obesity around the waist, high blood sugar and increased blood pressure. It is a known risk factor for heart disease, stroke and diabetes.

Previous studies have indicated that Toll-like receptor 4 (TLR4), a protein that activates inflammation after receiving chemical signals, may be at least partly responsible for the development of metabolic syndrome.

Researchers ran a series of experiments on both normal mice and mice genetically modified to lack TLR4 in their intestinal epithelium. They then fed both groups of mice "standard chow," or food with 22 percent fat calories, for 21 weeks.

Compared to normal mice, those lacking TLR4 showed a series of symptoms consistent with metabolic syndrome, such as significant weight gain, increased body and liver fat, and insulin resistance.

The researchers then fed both groups of mice a high-fat diet comprised of 60 percent fat calories for 21 weeks to find out whether diet would affect the development of metabolic syndrome. Again, the genetically modified mice gained significantly more in weight and had greater body and liver fat than the normal mice.

To confirm the role of TLR4 expression in the intestinal epithelium, the researchers genetically modified three more groups of mice: one group expressed TLR4 only in the intestinal epithelium, another group lacked TLR4 in all body cells and the third group lacked TLR4 only in white blood cells.

All groups ate standard chow, and all groups had similar body weight, body and liver fat, and glucose tolerance compared to normal mice.

Compared with normal mice, belly and small intestine fat was higher in mice lacking TLR4 only in the intestinal epithelium. This, the researchers say, provides further evidence that deleting TLR4 specifically from the intestinal epithelium is required for developing metabolic syndrome.

To investigate the role the bacterial makeup of the gut had on the mice, Hackam and his team then administered antibiotics to the normal and TLR4 intestinal epithelium-deficient mice. Antibiotics significantly reduced the amount of bacteria in the intestinal tract and prevented all symptoms of metabolic syndrome in the mice that lacked TLR4 in their intestinal epitheliums.

This demonstrates, the researchers say, that bacterial levels can be manipulated to prevent the development of metabolic syndrome.

The results were published in Mucosal Immunology.

Recent studies have found that gut bacteria have a role in many diseases. A study from the Mayo Clinic found that they predict our risk of rheumatoid arthritis. Researchers compared rheumatoid arthritis patients and their relatives to a healthy control group.

"Using genomic sequencing technology, we were able to pin down some gut microbes that were normally rare and of low abundance in healthy individuals, but expanded in patients with rheumatoid arthritis," said researcher Veena Taneja.

She added that in the future intestinal microbiota and metabolic signatures could help scientists build a predictive profile for who is likely to develop rheumatoid arthritis and the course the disease will take.

A recent study published in Movement Disorders found that bacteria in the guts of Parkinson's patients are very different from that of healthy people even at very early stages of the disease. Researchers hope their study may lead to earlier diagnosis of the disease, new treatments, and possibly even prevention.

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Researchers at Johns Hopkins have conducted a study that found that the intestinal microbe - the bacterial, viral, and fungal genes that make up the gut's biome - plays a significant role in the development of obesity and insulin resistance in mammals, including humans.The...
bacteria, gut, obesity, link, intestinal, microbe, biome
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2018-13-12
Monday, 12 February 2018 12:13 PM
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