Gut Microbiota Modulation of Host Feeding Behavior

Author: Ousey, James Anthony

Year: 2023

Degree: Dissertation (Ph.D.)

Advisor: Mazmanian, Sarkis K.

Committee Members: Prober, David A.; Lois, Carlos; Oka, Yuki; Mazmanian, Sarkis K.

Option: Biochemistry and Molecular Biophysics

DOI: 10.7907/8ghx-2b24

Abstract

The rich, diverse community of microorganisms in the gastrointestinal tract of animals, or gut microbiota, regulates aspects of host metabolism, immunity, and neural function, with resulting effects on the expression of complex behaviors, including feeding.

In this thesis, we sought to characterize gut microbiota influences on the behavioral response to palatable foods in mice. We discover that binge-like consumption of palatable foods, including high-sucrose pellets and a high-fat diet, is exacerbated in mice in the absence of a gut microbiota. Furthermore, using automated feeding dispensers and video analysis, we find that microbiota depletion with oral antibiotics results in elongated feeding bouts and conserved changes in the dynamics of palatable food intake. We show the hyperphagic phenotype of antibiotic-treated mice is reversible upon microbiota reconstitution via fecal microbiota transplant. Operant conditioning tests reveal that the motivation to pursue high-sucrose rewards is augmented in microbiota-depleted mice. The mesolimbic brain region activity induced upon high-sucrose pellet consumption is elevated in antibiotic-treated mice. Gut bacteria from the family S24-7 and genus Lactobacillus were identified by differential antibiotic treatment and fecal microbiota transplants as correlating with reduction of high-sucrose pellet consumption. Indeed, colonization of vancomycin-treated mice with a mixture of S24-7 and Lactobacillus johnsonii reduces overconsumption of high-sucrose pellets in a limited-access binge-eating model. The work in this thesis comprehensively demonstrates that the gut microbiota regulates feeding induced in response to palatable foods in mice.

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