Transfer with microbiota from lean donors prevents excessive weight gain and restores gut-brain vagal signaling in obese rats maintained on a high fat diet

TL;DR

Transferring gut bacteria from lean rats to obese ones on a high-fat diet reduces weight gain and improves gut-brain communication.

Contribution

This study shows that lean microbiota transfer can restore gut-brain signaling and reduce overeating in obese rats.

Findings

Transferring lean microbiota reduced caloric intake and prevented excessive weight gain in obese rats.

Lean microbiota transfer increased postprandial activation of gut and brainstem neurons in obese rats.

No significant changes in vagal afferent density were observed, but signaling improved in the HF-LF group.

Abstract

The collection of microorganisms, mainly bacteria, which live in the gastrointestinal (GI) tract are collectible known as the gut microbiota. GI bacteria play an active role in regulation of the host’s immune system and metabolism, as well as certain pathophysiological processes. Diet is the main factor modulating GI microbiota composition and recent studies have shown that high fat (HF) diets induce detrimental changes, known as dysbiosis, in the GI bacterial makeup. HF diet induced microbiota dysbiosis has been associated with structural and functional changes in gut-brain vagally mediated signaling system, associated with overeating and obesity. Although HF-driven changes in microbiota composition are sufficient to alter vagal signaling, it is unknown if restoring normal microbiota in obesity can improve gut-brain signaling and metabolic outcomes. In this study, we evaluated the effect of lean gut microbiota transfer in obese, vagally compromised, rats on gut-brain communication, food intake, and body weight. Male Sprague-Dawley rats were maintained on regular chow, or 45% HF diet for nine weeks followed by three weeks of microbiota depletion using an antibiotic cocktail. The animals were then divided into four groups (n=10 each): LF – control group on regular chow, LF-LF – chow fed animals that received antibiotics and microbiota from chow fed animals, HF-LF – HF fed animals that received microbiota from chow fed animals, and HF-HF – HF fed animals that received microbiota from HF fed animals. Animals were gavaged with donor microbiota for three consecutive days on week one and once a week thereafter for three more weeks. HF-LF animals received inulin as a prebiotic to aid the establishment of the lean microbiome.

We found that transferring a LF microbiota to HF fed animals (HF-LF) reduced caloric intake during the light phase when compared with HF-HF rats and prevented additional excessive weight gain. We did not observe significant changes in the density of vagal afferents terminating in the brainstem among the groups, however, HF-LF animals displayed an increase in postprandial activation of both primary sensory neurons innervating the GI tract and brainstem secondary neurons.

We concluded from these data that normalizing microbiota composition in obese rats improves gut-brain communication and restores normal feeding patterns which was associated with a reduction in weight gain.

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