Gut microbiota and short-chain fatty acids may be new biomarkers for predicting neonatal necrotizing enterocolitis: A pilot study

Abstract

BackgroundDysbacteriosis is thought to play an important role in the pathogenesis of necrotizing enterocolitis (NEC). We aimed to identify new biomarkers among gut microbiota and short-chain fatty acids (SCFAs) for the early prediction of NEC.Materials and methodsThirty-four preterm infants with gestational ages of ≤ 34 weeks who developed gastrointestinal symptoms were divided into the NEC group (n = 17) and non-NEC group (n = 17). In the NEC group, the gut microbiota and SCFAs in feces were assessed when the infants were enrolled (Group P) and when they were diagnosed with NEC (Group N). In the non-NEC group, samples were assessed when the infants were enrolled (Group C).ResultsThe Ace and Chao1 indices were higher in Group P than in Group C (P < 0.05), and there was no difference between Groups C and N or between Groups P and N (P > 0.05). There was no significant difference in the Simpson and Shannon indices among Groups C, P and N (P > 0.05). The four main phyla showed no differences (P > 0.05) in composition, while at the genus level, compared with Group C, in Group P, Clostridioides, Blautia and Clostridium_sensu_stricto_1 were increased, while Lactobacillus and Bifidobacterium were decreased (P < 0.05). At the species level, Streptococcus salivarius and Rothia mucilaginosa increased, while Bifidobacterium animals subsp. lactis decreased (P < 0.05). In Group N, at the genus level, Stenotrophomonas, Streptococcus and Prevotella increased (P < 0.05). Compared with those in Group C, the levels of acetic acid, propanoic acid and butyric acid decreased significantly in Groups P and N (P < 0.05), and the areas under the curves (AUCs) of these three SCFAs between groups C and P were 0.73, 0.70, and 0.68, respectively.ConclusionThe increase in Streptococcus salivarius and Rothia mucilaginosa and decrease in Bifidobacterium_animals_subsp._lactis, as well as the decrease in acetic, propionic and butyric acids, may help in the early prediction of NEC.

Succinate aggravates intestinal injury in mice with necrotizing enterocolitis

“…Substantial evidence has indicated that succinate concentrations increase under conditions of hypoxia, stress, inflammation, and changes in intestinal microorganisms ( Nagao-Kitamoto et al., 2016 ; Macias-Ceja et al., 2019 ; Banerjee et al., 2020 ; Huber-Ruano et al., 2022 ). It has been widely reported in previous studies that changes in the intestinal flora are closely related to the development of NEC ( He et al., 2021 ; Liu et al., 2022a ; Samara et al., 2022 ). In exploring the pathological mechanism whereby the gut flora affects NEC, some investigators have proven that gut microbiota-derived metabolites, including short-chain fatty acids, DL-lactate, tauroursodeoxycholic acid, and other related metabolites, play important messenger roles in NEC progression or can contribute to its prediction ( Li et al., 2019a ; Feng et al., 2022 ; Huang et al., 2022 ).…”

“…Additionally, with the change in the gut microbiota, metabolites show corresponding changes; the affected metabolites are generally considered to act as a bridge between flora and host communication and may also be involved in the pathogenesis of NEC (Krautkramer et al, 2021;Zhou et al, 2022a). For example, several studies have demonstrated the effect of short-chain fatty acids on the progression of intestinal health in patients with NEC and demonstrated that they show predictive value for NEC development (Roy et al, 2018;Sun et al, 2021;Liu et al, 2022a). Succinate, widely regarded as an intermediate molecule of the mitochondrial tricarboxylic acid cycle, has recently emerged as a key player in maintaining intestinal homeostasis, intestinal energy metabolism, and immune regulation (De Vadder et al, 2016;Banerjee et al, 2020;Zhou et al, 2022b).…”

“…Additionally, with the change in the gut microbiota, metabolites show corresponding changes; the affected metabolites are generally considered to act as a bridge between flora and host communication and may also be involved in the pathogenesis of NEC ( Krautkramer et al., 2021 ; Zhou et al., 2022a ). For example, several studies have demonstrated the effect of short-chain fatty acids on the progression of intestinal health in patients with NEC and demonstrated that they show predictive value for NEC development ( Roy et al., 2018 ; Sun et al., 2021 ; Liu et al., 2022a ).…”

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

“…Preterm infants demonstrated a significantly less diverse microbiome, including Bifidobacterium spp. [ 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. Bifidobacterium spp.…”

“…The aetiology of NEC is not clear, but it is thought to be related to several factors, including pre-eclampsia, aberrant bacterial colonization (e.g., infection), premature rupture of the membranes, placental abruption, intrauterine growth restriction, LBW, patent ductus arteriosus, sepsis and anemia [ 13 ]. Early gut microbial dysbiosis is also implicated in disease pathogenesis, in which the gut microbiota composition of preterm infants with NEC is characterized by reduced abundances of Bifidobacterium , Firmicutes and Bacteroidetes and increased abundances of Prevotella , Clostridioides , Staphylococcaceae , Proteobacteria , Enterobacteriaceae , Rothia , Streptococcus and Blautia [ 14 , 15 , 16 , 17 , 18 , 19 , 20 ].…”