Interplay of intestinal bacteria, host cells affects body weight



Mysterious cells that secrete hormones in the large intestine play a key role in regulating body weight through their relationship with intestinal bacteria, a study led by researchers suggests. Their findings, published in Nature Metabolism, could lead to new treatments for obesity and extreme weight loss.

“This work provides a new understanding of the complex metabolic interplay between bacteria and the host, shedding light on novel mechanisms that control appetite and body weight,” said the senior author.

For about a century, scientists have known that the lining of the intestines contains hormone-producing cells known as enteroendocrine cells (EECs). In the small intestine, EECs sense nutrients passing through the organ and secrete hormones that control digestion and absorption. However, since the large intestine is thought to mostly absorb water and salt, the role of EECs there has been unclear.

To investigate, the researchers used a targeted genetic technique to prevent this type of cell from developing in the large intestine, also known as the colon, of lab mice. As these animals grew into adulthood, they gradually became obese from overeating and developed changes that accompany obesity, including poor blood sugar control. Tests showed these mice had elevated amounts of glutamate in their stool. Other experiments showed that this amino acid influences appetite in the brain, an effect not previously known.

Surprisingly, the extra glutamate stemmed not from intestines without EECs but from intestinal bacteria, whose composition became different in the genetically altered mice compared with unaltered littermates. Supplementing unaltered mice with glutamate increased their appetites similarly to animals in which EECs in the colon had been deleted.

Together, the senior author these findings suggest that interplay between colonic EECs and intestinal bacteria regulates the intestinal flora’s composition, affecting how much glutamate these microbes secrete – and, in turn, influencing the host animal’s appetite.

Eventually, researchers may be able to create treatments for obesity based on these findings by decreasing intestinal glutamate or for extreme weight loss disorders such as anorexia nervosa by increasing this amino acid.

In the meantime, the researchers are investigating several questions, including how EECs communicate with intestinal bacteria and how glutamate produced in the intestines sends a signal to the appetite-regulating center in the brain.

https://www.nature.com/articles/s42255-024-01044-5

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