Therapeutic Potential of Gut Microbiota and Its Metabolite Short-Chain Fatty Acids in Neonatal Necrotizing Enterocolitis

Abstract

Short chain fatty acids (SCFAs), the principle end-products produced by the anaerobic gut microbial fermentation of complex carbohydrates (CHO) in the colon perform beneficial roles in metabolic health. Butyrate, acetate and propionate are the main SCFA metabolites, which maintain gut homeostasis and host immune responses, enhance gut barrier integrity and reduce gut inflammation via a range of epigenetic modifications in DNA/histone methylation underlying these effects. The infant gut microbiota composition is characterized by higher abundances of SCFA-producing bacteria. A large number of in vitro/vivo studies have demonstrated the therapeutic implications of SCFA-producing bacteria in infant inflammatory diseases, such as obesity and asthma, but the application of gut microbiota and its metabolite SCFAs to necrotizing enterocolitis (NEC), an acute inflammatory necrosis of the distal small intestine/colon affecting premature newborns, is scarce. Indeed, the beneficial health effects attributed to SCFAs and SCFA-producing bacteria in neonatal NEC are still to be understood. Thus, this literature review aims to summarize the available evidence on the therapeutic potential of gut microbiota and its metabolite SCFAs in neonatal NEC using the PubMed/MEDLINE database.

The role of short-chain fatty acids produced by gut microbiota in the regulation of pre-eclampsia onset

“…In term infants born to GDM women, GM, such as Bifidobacterium, is related to the decrease of SCFAs content in feces ( Soderborg et al., 2020 ). Bifidobacterium can utilize human milk oligosaccharides (HMOs) through related degradation enzymes, thereby increasing the production of butyrate, propionate and other SCFAs ( Gopalsamy et al., 2019 ; Alsharairi, 2023 ). The results of a control trial showed that butyrate could reduce intestinal inflammation in mice, and the expression of M2 macrophage related protein Arg1 was significantly increased.…”

The Role of Diet and Nutritional Interventions for the Infant Gut Microbiome

“…In agreement with the typical gut microbiota developmental pattern, key species within the Lachnospiraceae and Ruminococcaceae families produce butyrate, while Bacteroides species are common propionate producers [161]. These species possess a comprehensive array of enzymes for breaking down dietary fibers into these SCFAs [162]. Moreover, certain species more abundant in older infants, such as Bacteroides and Clostridium, might employ a range of amino acids derived from dietary proteins to produce BCFAs [163].…”

Short-chain fatty acids in nonalcoholic fatty liver disease: New prospects for short-chain fatty acids as therapeutic targets

“…The change in DNA methylation induced by SCFAs is an important epigenetic modification [ 67 ]. During the occurrence and development of NAFLD, the hypo-and hypermethylation genes such as growth factor-α ( PDGFα ), phospholipase C gamma 1 ( PLCG1 ), caspase 1 ( CASP1 ) are epigenetic regulated and exacerbate the progression of NAFLD by participating in immune response, oxidative stress, and liver lipid degeneration [ 68 ].…”