Fructooligosaccharides and galactooligosaccharides improve hepatic steatosis via gut microbiota-brain axis modulation

AbstractStudies have shown that gut dysbiosis is associated with the steatotic liver disease associated with metabolic dysfunction (MALSD) and its severity. This study evaluated the effects of two commercially available prebiotics fructooligosaccharides (FOS) and galactooligosaccharides(GOS) on hepatic adipogenesis, inflammation, and gut microbiota in high-fat diet-induced MALSD. The results indicated that FOS and GOS effectively reduced insulin resistance, hyperglycaemia, triglyceridemia, cholesterolaemia, and IL-1β serum levels. Moreover, FOS and GOS modulated the lipogenic (SREBP-1c, ACC, and FAS) and lipolytic (ATGL) signalling pathways, and reduced inflammatory markers such as p-NFκB-65, IL-6, iNOS, COX-2, TNF-α, IL-1β, and nitrotyrosine. FOS and GOS also enhanced the abundance of acetate producers’ bacteria Bacteroides acidifaciens and Bacteroides dorei. FOS and GOS also induced positive POMC/GPR43 neurons at the arcuate nucleus, indicating hypothalamic signalling modulation. Our results suggest that FOS and GOS attenuated MALSD by reducing the hepatic lipogenic pathways and intestinal permeability through the gut microbiota-brain axis.Keywords: FOS and GOSMASLDadipogenesisgut microbiotaPOMC AcknowledgementsThe authors would like to express their gratitude to the Research Excellence Program - Instituto Aggeu Magalhães (IAM-PROEP#400208/2019-9), the Knowledge Generation Program of the Fundação Oswaldo Cruz (FIOCRUZ; #VPPCB-007-FIO-18-2-17), the Institute of Science and Technology of Neuroimmunomodulation (INCT-NIM; # 465489/2014-1) and the National Council for Scientific and Technological Development (CNPq; #301777/2012-8). This study was partially funded by the Coordination for the Improvement of Higher Education Personnel-Brazil (CAPES) Financial Code 001. All authors contributed to the preparation of the manuscript and approved its final version. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.Author contributionsR.S.S performed experiments, analysed data and wrote the manuscript. I.P.M; I.H.R.P performed experiments. J.R.B.S. performed statistical analyses. C.A.P. conceived, supervised, and reviewed the manuscript.Disclosure statementThe authors declare that there was no conflict of interest concerning the publication of this article.Consent formInformed consent was obtained from all subjects involved in the study.Data availabilityData supporting findings are presented within the manuscript. Inquiries about data availability should be directed to the authors.Additional informationFundingThis work was supported by Aggeu Magalhães Institute, Fundação Oswaldo Cruz.