Infant Feces-derived FWJL-4 Mitigates Experimental Necrotizing Enterocolitis Acetate Production

Overview

Journal Gut Microbes

Specialties Gastroenterology
Microbiology

Date 2024 Dec 8

PMID 39648298

Authors

Li-Long Pan

Yudong Sun

Xiaoliang Dong

Zhengnan Ren

Binbin Li

Ping Yang

Le Zhang

Jia Sun

Affiliations

Soon will be listed here.

Abstract

Necrotizing enterocolitis (NEC) is a life-threatening disease in premature infants, characterized by high mortality. Recent studies increasingly highlight the role of gut dysbiosis in NEC pathogenesis. Although probiotics have shown some efficacy in preventing NEC, further research is needed to determine potential strains and approaches. In this study, we demonstrated that the novel probiotic strain () FWJL-4, isolated from the feces of healthy infants, significantly enhanced intestinal barrier function, providing substantial protection against NEC. This protective effect was attributed to elevated intestinal acetate levels. Notably, acetate supplementation alone was sufficient to mitigate NEC, mimicking the protective effects of FWJL-4. Mechanistically, we revealed that FWJL-4 inhibited necroptosis and preserved the number of the goblet cells and enterocytes through the production of the short-chain fatty acid acetate, activation of the acetate receptors G protein-coupled receptor (GPR) 41 and GPR43. Our findings suggest that FWJL-4 enhances intestinal barrier function to protect against NEC, underscoring the potential of probiotic manipulation as a promising strategy for NEC prevention.

References

MohanKumar K, Namachivayam K, Cheng F, Jiang R, Flores-Torres J, Torres B . Trinitrobenzene sulfonic acid-induced intestinal injury in neonatal mice activates transcriptional networks similar to those seen in human necrotizing enterocolitis. Pediatr Res. 2016; 81(1-1):99-112. PMC: 5235988. DOI: 10.1038/pr.2016.189. View

MohanKumar K, Kaza N, Jagadeeswaran R, Garzon S, Bansal A, Kurundkar A . Gut mucosal injury in neonates is marked by macrophage infiltration in contrast to pleomorphic infiltrates in adult: evidence from an animal model. Am J Physiol Gastrointest Liver Physiol. 2012; 303(1):G93-102. PMC: 3404576. DOI: 10.1152/ajpgi.00016.2012. View

Lin P, Myers L, Ray L, Song S, Nasr T, Berardinelli A . Lactobacillus rhamnosus blocks inflammatory signaling in vivo via reactive oxygen species generation. Free Radic Biol Med. 2009; 47(8):1205-11. PMC: 2760264. DOI: 10.1016/j.freeradbiomed.2009.07.033. View

Nino D, Sodhi C, Hackam D . Necrotizing enterocolitis: new insights into pathogenesis and mechanisms. Nat Rev Gastroenterol Hepatol. 2016; 13(10):590-600. PMC: 5124124. DOI: 10.1038/nrgastro.2016.119. View

Ikeda T, Nishida A, Yamano M, Kimura I . Short-chain fatty acid receptors and gut microbiota as therapeutic targets in metabolic, immune, and neurological diseases. Pharmacol Ther. 2022; 239:108273. DOI: 10.1016/j.pharmthera.2022.108273. View

Kimura I, Ichimura A, Ohue-Kitano R, Igarashi M . Free Fatty Acid Receptors in Health and Disease. Physiol Rev. 2019; 100(1):171-210. DOI: 10.1152/physrev.00041.2018. View

Olm M, Bhattacharya N, Crits-Christoph A, Firek B, Baker R, Song Y . Necrotizing enterocolitis is preceded by increased gut bacterial replication, , and fimbriae-encoding bacteria. Sci Adv. 2019; 5(12):eaax5727. PMC: 6905865. DOI: 10.1126/sciadv.aax5727. View

Alcon-Giner C, Dalby M, Caim S, Ketskemety J, Shaw A, Sim K . Microbiota Supplementation with and Modifies the Preterm Infant Gut Microbiota and Metabolome: An Observational Study. Cell Rep Med. 2020; 1(5):100077. PMC: 7453906. DOI: 10.1016/j.xcrm.2020.100077. View

Pammi M, Cope J, Tarr P, Warner B, Morrow A, Mai V . Intestinal dysbiosis in preterm infants preceding necrotizing enterocolitis: a systematic review and meta-analysis. Microbiome. 2017; 5(1):31. PMC: 5343300. DOI: 10.1186/s40168-017-0248-8. View

10.

Macia L, Tan J, Vieira A, Leach K, Stanley D, Luong S . Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome. Nat Commun. 2015; 6:6734. DOI: 10.1038/ncomms7734. View

11.

Gustafsson J, Johansson M . The role of goblet cells and mucus in intestinal homeostasis. Nat Rev Gastroenterol Hepatol. 2022; 19(12):785-803. DOI: 10.1038/s41575-022-00675-x. View

12.

Blum L, Vincent D, Boettcher M, Knopf J . Immunological aspects of necrotizing enterocolitis models: a review. Front Immunol. 2024; 15:1434281. PMC: 11298363. DOI: 10.3389/fimmu.2024.1434281. View

13.

Collado M, Cernada M, Neu J, Perez-Martinez G, Gormaz M, Vento M . Factors influencing gastrointestinal tract and microbiota immune interaction in preterm infants. Pediatr Res. 2015; 77(6):726-31. DOI: 10.1038/pr.2015.54. View

14.

Bauer P, Duca F, Waise T, Dranse H, Rasmussen B, Puri A . Lactobacillus gasseri in the Upper Small Intestine Impacts an ACSL3-Dependent Fatty Acid-Sensing Pathway Regulating Whole-Body Glucose Homeostasis. Cell Metab. 2018; 27(3):572-587.e6. DOI: 10.1016/j.cmet.2018.01.013. View

15.

Liu X, Du T, Gao X, Zhao W, Wang Z, He Y . Gut microbiota and short-chain fatty acids may be new biomarkers for predicting neonatal necrotizing enterocolitis: A pilot study. Front Microbiol. 2022; 13:969656. PMC: 9428482. DOI: 10.3389/fmicb.2022.969656. View

16.

De Filippis F, Pasolli E, Ercolini D . The food-gut axis: lactic acid bacteria and their link to food, the gut microbiome and human health. FEMS Microbiol Rev. 2020; 44(4):454-489. PMC: 7391071. DOI: 10.1093/femsre/fuaa015. View

17.

Pan L, Ren Z, Yang J, Li B, Huang Y, Song D . Gut microbiota controls the development of chronic pancreatitis: A critical role of short-chain fatty acids-producing Gram-positive bacteria. Acta Pharm Sin B. 2023; 13(10):4202-4216. PMC: 10547962. DOI: 10.1016/j.apsb.2023.08.002. View

18.

Hui Y, Smith B, Steen Mortensen M, Krych L, Sorensen S, Greisen G . The effect of early probiotic exposure on the preterm infant gut microbiome development. Gut Microbes. 2021; 13(1):1951113. PMC: 8284123. DOI: 10.1080/19490976.2021.1951113. View

19.

Li B, Lee C, Chuslip S, Lee D, Biouss G, Wu R . Intestinal epithelial tight junctions and permeability can be rescued through the regulation of endoplasmic reticulum stress by amniotic fluid stem cells during necrotizing enterocolitis. FASEB J. 2020; 35(1):e21265. DOI: 10.1096/fj.202001426R. View

20.

Cuna A, Morowitz M, Ahmed I, Umar S, Sampath V . Dynamics of the preterm gut microbiome in health and disease. Am J Physiol Gastrointest Liver Physiol. 2021; 320(4):G411-G419. PMC: 8238167. DOI: 10.1152/ajpgi.00399.2020. View