“Butyrate, produced from dietary fiber by the gut flora, can enter the brain and directly regulate appetite – a novel finding that expands our understanding on the gut – brain axis”. The finding is reported in a recent study published in Nature Communications by a group of researchers including Dr. Doan Van Khanh – School of Health Sciences at Eastern International University (EIU), as one of the four primary authors.
The research article, titled “Primary Cilia of Hypothalamic AgRP Neurons Regulate the Metabolic Effects of Butyrate,” shows that butyrate, a short-chain fatty acid (SCFA) produced by gut bacteria, affects the host body’s metabolism not only in the gastrointestinal tract but also in the brain, particularly in the regulation of appetite and energy balance. However, the central nervous system mechanisms underlying these effects of butyrate remain unclear. In this study, the authors demonstrate that the primary cilia of agouti-related peptide (AgRP)-secreting neurons in the arcuate nucleus of the hypothalamus are required for butyrate’s appetite-suppressing effects and its role in regulating glucose homeostasis. Specifically, the administration of butyrate to mice, either peripherally or directly into the brain, increased ciliogenesis in hypothalamic neurons. This may occur through enhanced histone acetylation and the activation of transcription factors that regulate the expression of genes involved in primary cilia formation, thereby reducing food intake and improving metabolism. Disrupting the structure and function of primary cilia in hypothalamic neurons—specifically in AgRP neurons of the arcuate nucleus, but not in midbrain neurons—abolished the effects of butyrate. At the cellular level, butyrate inhibited AgRP neuronal activity, and this inhibitory effect was markedly reduced when the neurons lost their primary cilia, indicating that primary cilia determine the neuronal inhibitory effects of butyrate. These findings establish the essential role of primary cilia in AgRP neurons in mediating the metabolic effects of butyrate.
Access full article: https://doi.org/10.1038/s41467-026-71745-w
Dr. Doan Van Khanh – School of Health Sciences at EIU
Regarding its scientific significance and novelty, we all know that consuming enough dietary fiber helps reduce overeating tendencies, support weight management, and control blood glucose levels. Many previous studies have shown that these beneficial metabolic effects of adequate fiber intake result from multiple mechanisms. Dietary fiber is not digested in the stomach or small intestine. Therefore, when consumed, it helps create a longer-lasting feeling of fullness by stimulating intestinal cells to secrete hormones such as cholecystokinin (CCK) and peptide tyrosine tyrosine (PYY), which reduce appetite and food cravings (J. Gibbs, October 12, 1973; Dagbasi, June 19, 2024), thereby lowering food intake. In addition, when fiber reaches the large intestine, it is partially metabolized by gut bacteria, producing short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate. These SCFAs are absorbed into the circulatory system and transported throughout the body via the bloodstream, influencing the metabolism of various organs. Among them, butyrate has the highest potential to cross the blood-brain barrier and act directly on neurons (O’Riordan, April 2022), particularly hypothalamic neurons surrounding the third ventricle, which play an especially important role in regulating whole-body homeostasis, including metabolic, endocrine, and neural functions. Currently, these short-chain fatty acids are being studied for supplementation in diets, including infant formula products, with the aim of improving human digestive health, immune function, and neurocognitive development (Stinson, July 21, 2020; Paparo, May 2021). Therefore, gaining a deeper understanding of the mechanisms through which SCFAs, particularly butyrate, affect cellular metabolism in the body—especially in neurons—is both necessary and important. This represents the key novelty and critical contribution of the study, which led to its acceptance for publication in a leading multidisciplinary scientific journal such as Nature Communications.
The paper was completed and published during my time working at Eastern International University (EIU). Therefore, acknowledging EIU in the publication not only reflects transparency in scientific activities but also represents my personal responsibility to contribute to the University’s overall development. At present, in alignment with the University’s orientation in training and scientific and technological development in the field of Health Sciences, I am gradually shifting my research focus from basic biomedical research to translational and clinical research. This is a challenging journey, but also one full of opportunities. With personal determination and support from the University, I hope that in the future I will be able to conduct research projects whose outcomes are fully developed and shaped at EIU.
Reference:
- Dagbasi, Aygul. 2024 Jun 19. “Diet shapes the metabolite profile in the intact human ileum, which affects PYY release.” Science Translational Medicine 16(752):eadm8132. doi: 10.1126/scitranslmed.adm8132.
- J Gibbs, R C Young, G P Smith. 1973 Oct 12. “Cholecystokinin elicits satiety in rats with open gastric fistulas.” Nature 245(5424):323-5. doi: 10.1038/245323a0.
- O’Riordan, Kenneth J. 2022 April. “Short chain fatty acids: Microbial metabolites for gut-brain axis signalling.” Molecular and Cellular Endocrinology 15:546:111572. doi: 10.1016/j.mce.2022.111572.
- Paparo, Lorella. 2021 May. “Butyrate as a bioactive human milk protective component against food allergy.” Allergy 76(5):1398-1415. doi: 10.1111/all.14625.
- Stinson, Lisa F. 2020 Jul 21. “Human Milk From Atopic Mothers Has Lower Levels of Short Chain Fatty Acids.” Frontier Immunology 11:1427. doi: 10.3389/fimmu.2020.01427.
