Influence of the gut microbiome on appetite-regulating neuropeptides in the hypothalamus: Insight from conventional, antibiotic-treated, and germ-free mouse models of anorexia nervosa

• Published in: Neurobiology of disease Vol. 193; p. 106460
• Main Authors: Roubalová, Radka, Procházková, Petra, Kovářová, Tereza, Ježková, Janet, Hrnčíř, Tomáš, Tlaskalová-Hogenová, Helena, Papežová, Hana
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2024; Elsevier
• Subjects: Activity-based anorexia model; Animals; Anorexia Nervosa - metabolism; Appetite - physiology; Appetite regulation; Eating disorders; Gastrointestinal Microbiome; Gut barrier; Humans; Hypothalamus - metabolism; Mice; Microbiome; Neuropeptide Y; Neuropeptides - metabolism; Neuropeptide Y; Activity-based anorexia model; Appetite regulation; Eating disorders; Gut barrier; Microbiome
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2024.106460

Recent research highlights the profound impact of the gut microbiome on neuropsychiatric disorders, shedding light on its potential role in shaping human behavior. In this study, we investigate the role of the gut microbiome in appetite regulation using activity-based anorexia (ABA) mouse model of anorexia nervosa (AN) — a severe eating disorder with significant health consequences. ABA was induced in conventional, antibiotic-treated, and germ-free mice. Our results show the clear influence of the gut microbiome on the expression of four orexigenic (neuropeptide Y, agouti-related peptide, melanin-concentrating hormone, and orexin) and four anorexigenic peptides (cocaine- and amphetamine-regulated transcript, corticotropin-releasing hormone, thyrotropin-releasing hormone, and pro-opiomelanocortin) in the hypothalamus. Additionally, we assessed alterations in gut barrier permeability. While variations were noted in germ-free mice based on feeding and activity, they were not directly attributable to the gut microbiome. This research emphasizes that the gut microbiome is a pivotal factor in AN's appetite regulation beyond just dietary habits or physical activity. •The gut microbiome contributes to the exercise capacity of mice.•ATB administration decrease the running activity of activity-based anorexia mice.•The gut microbiome has an impact on the expression of feeding-regulatory peptides.•Antibiotics downregulate the expression of key neuropeptides regulating appetite.