From Gut to Brain: The Impact of Short-Chain Fatty Acids on Brain Cancer

Overview

Journal Neuromolecular Med

Date 2025 Jan 17

PMID 39821841

Authors

Mohamed J Saadh

Omer Qutaiba B Allela

Radhwan Abdul Kareem

Gaurav Sanghvi

Soumya V Menon

Pawan Sharma

Balvir S Tomar

Aanchal Sharma

Hayder Naji Sameer

Atheer Khdyair Hamad

Zainab H Athab

Mohaned Adil

Affiliations

Soon will be listed here.

Abstract

The primary source of short-chain fatty acids (SCFAs), now recognized as critical mediators of host health, particularly in the context of neurobiology and cancer development, is the gut microbiota's fermentation of dietary fibers. Recent research highlights the complex influence of SCFAs, such as acetate, propionate, and butyrate, on brain cancer progression. These SCFAs impact immune modulation and the tumor microenvironment, particularly in brain tumors like glioma. They play a critical role in regulating cellular processes, including apoptosis, cell differentiation, and inflammation. Moreover, studies have linked SCFAs to maintaining the integrity of the blood-brain barrier (BBB), suggesting a protective role in preventing tumor infiltration and enhancing anti-tumor immunity. As our understanding of the gut-brain axis deepens, it becomes increasingly important to investigate SCFAs' therapeutic potential in brain cancer management. Looking into how SCFAs affect brain tumor cells and the environment around them could lead to new ways to prevent and treat these diseases, which could lead to better outcomes for people who are dealing with these challenging cancers.

References

Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J, deRoos P . Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 2013; 504(7480):451-5. PMC: 3869884. DOI: 10.1038/nature12726. View

Baruch E, Youngster I, Ben-Betzalel G, Ortenberg R, Lahat A, Katz L . Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients. Science. 2020; 371(6529):602-609. DOI: 10.1126/science.abb5920. View

Berndt B, Zhang M, Owyang S, Cole T, Wang T, Luther J . Butyrate increases IL-23 production by stimulated dendritic cells. Am J Physiol Gastrointest Liver Physiol. 2012; 303(12):G1384-92. PMC: 3532546. DOI: 10.1152/ajpgi.00540.2011. View

Bhat M, Kapila R . Dietary metabolites derived from gut microbiota: critical modulators of epigenetic changes in mammals. Nutr Rev. 2017; 75(5):374-389. DOI: 10.1093/nutrit/nux001. View

Borre Y, OKeeffe G, Clarke G, Stanton C, Dinan T, Cryan J . Microbiota and neurodevelopmental windows: implications for brain disorders. Trends Mol Med. 2014; 20(9):509-18. DOI: 10.1016/j.molmed.2014.05.002. View

Braniste V, Al-Asmakh M, Kowal C, Anuar F, Abbaspour A, Toth M . The gut microbiota influences blood-brain barrier permeability in mice. Sci Transl Med. 2014; 6(263):263ra158. PMC: 4396848. DOI: 10.1126/scitranslmed.3009759. View

Brennan C, Verhaak R, McKenna A, Campos B, Noushmehr H, Salama S . The somatic genomic landscape of glioblastoma. Cell. 2013; 155(2):462-77. PMC: 3910500. DOI: 10.1016/j.cell.2013.09.034. View

Brown A, Goldsworthy S, Barnes A, Eilert M, Tcheang L, Daniels D . The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem. 2002; 278(13):11312-9. DOI: 10.1074/jbc.M211609200. View

Cani P, Lecourt E, Dewulf E, Sohet F, Pachikian B, Naslain D . Gut microbiota fermentation of prebiotics increases satietogenic and incretin gut peptide production with consequences for appetite sensation and glucose response after a meal. Am J Clin Nutr. 2009; 90(5):1236-43. DOI: 10.3945/ajcn.2009.28095. View

10.

Chen L, Sun M, Wu W, Yang W, Huang X, Xiao Y . Microbiota Metabolite Butyrate Differentially Regulates Th1 and Th17 Cells' Differentiation and Function in Induction of Colitis. Inflamm Bowel Dis. 2019; 25(9):1450-1461. PMC: 6701512. DOI: 10.1093/ibd/izz046. View

11.

Chen M, Sundrud M . Cytokine Networks and T-Cell Subsets in Inflammatory Bowel Diseases. Inflamm Bowel Dis. 2016; 22(5):1157-67. PMC: 4838490. DOI: 10.1097/MIB.0000000000000714. View

12.

Chen Y, Chen Y, Zhang J, Cao P, Su W, Deng Y . Promotes Metastasis in Colorectal Cancer by Activating Autophagy Signaling via the Upregulation of CARD3 Expression. Theranostics. 2020; 10(1):323-339. PMC: 6929621. DOI: 10.7150/thno.38870. View

13.

Coutzac C, Jouniaux J, Paci A, Schmidt J, Mallardo D, Seck A . Systemic short chain fatty acids limit antitumor effect of CTLA-4 blockade in hosts with cancer. Nat Commun. 2020; 11(1):2168. PMC: 7195489. DOI: 10.1038/s41467-020-16079-x. View

14.

DAgostino P, Gottfried-Blackmore A, Anandasabapathy N, Bulloch K . Brain dendritic cells: biology and pathology. Acta Neuropathol. 2012; 124(5):599-614. PMC: 3700359. DOI: 10.1007/s00401-012-1018-0. View

15.

DAlessandro G, Antonangeli F, Marrocco F, Porzia A, Lauro C, Santoni A . Gut microbiota alterations affect glioma growth and innate immune cells involved in tumor immunosurveillance in mice. Eur J Immunol. 2020; 50(5):705-711. PMC: 7216943. DOI: 10.1002/eji.201948354. View

16.

Davie J . Inhibition of histone deacetylase activity by butyrate. J Nutr. 2003; 133(7 Suppl):2485S-2493S. DOI: 10.1093/jn/133.7.2485S. View

17.

deFazio A, Chiew Y, Donoghue C, Lee C, Sutherland R . Effect of sodium butyrate on estrogen receptor and epidermal growth factor receptor gene expression in human breast cancer cell lines. J Biol Chem. 1992; 267(25):18008-12. View

18.

Dinan T, Stilling R, Stanton C, Cryan J . Collective unconscious: how gut microbes shape human behavior. J Psychiatr Res. 2015; 63:1-9. DOI: 10.1016/j.jpsychires.2015.02.021. View

19.

Dokmanovic M, Marks P . Prospects: histone deacetylase inhibitors. J Cell Biochem. 2005; 96(2):293-304. DOI: 10.1002/jcb.20532. View

20.

Du H, Yue S, Niu D, Liu C, Zhang L, Chen J . Gut Microflora Modulates Th17/Treg Cell Differentiation in Experimental Autoimmune Prostatitis the Short-Chain Fatty Acid Propionate. Front Immunol. 2022; 13:915218. PMC: 9289123. DOI: 10.3389/fimmu.2022.915218. View