Gut Dysbiosis With Bacilli Dominance and Accumulation of Fermentation Products Precedes Late-onset Sepsis in Preterm Infants

Abstract

Background Gut dysbiosis has been suggested as a major risk factor for the development of late-onset sepsis (LOS), a main cause of mortality and morbidity in preterm infants. We aimed to assess specific signatures of the gut microbiome, including metabolic profiles, in preterm infants <34 weeks of gestation preceding LOS. Methods In a single-center cohort, fecal samples from preterm infants were prospectively collected during the period of highest vulnerability for LOS (days 7, 14, and 21 of life). Following 16S rRNA gene profiling, we assessed microbial community function using microbial metabolic network modeling. Data were adjusted for gestational age and use of probiotics. Results We studied stool samples from 71 preterm infants with LOS and 164 unaffected controls (no LOS/necrotizing enterocolitis). In most cases, the bacteria isolated in diagnostic blood culture corresponded to the genera in the gut microbiome. LOS cases had a decelerated development of microbial diversity. Before onset of disease, LOS cases had specific gut microbiome signatures with higher abundance of Bacilli (specifically coagulase-negative Staphylococci) and a lack of anaerobic bacteria. In silico modeling of bacterial community metabolism suggested accumulation of the fermentation products ethanol and formic acid in LOS cases before the onset of disease. Conclusions Intestinal dysbiosis preceding LOS is characterized by an accumulation of Bacilli and their fermentation products and a paucity of anaerobic bacteria. Early microbiome and metabolic patterns may become a valuable biomarker to guide individualized prevention strategies of LOS in highly vulnerable populations.

Metabolic Functions of Gut Microbes Associate With Efficacy of Tumor Necrosis Factor Antagonists in Patients With Inflammatory Bowel Diseases

“…37,38 These findings do not only support the crucial role of SCFA in the disease control of patients with IBD but also underline the feasibility of using 16S in silico analysis to predict metabolic pathways that are disrupted in IBD and might affect therapeutic efficacy, which has also been suggested by others. 39,40 It is tempting to speculate on the mechanism of action by which biologic therapy is able to restore metabolite exchange interactions in IBD. A robust clinical response to biologic therapy leads to mucosal healing, inducing subsequent changes in host transcriptome architecture.…”

Lactobacillus Acidophilus/Bifidobacterium Infantis Probiotics Are Beneficial to Extremely Low Gestational Age Infants Fed Human Milk

“…While the huge variability in study designs has been acknowledged, the authors conclude that probiotics are more effective in reducing morbidity when taken in human milk or human milk plus formula form, consumed for <6 weeks, administered at a dosage of <10 9 CFU/d, and include multiple strains. We assume that promoted weight gain in HM-fed infants is correlated with the dynamics of the establishing intestinal microbiota, nutrient utilization, and immune-metabolome interaction [4,32]. L. acidophilus/B.…”

“…Probiotics that act as gut colonizers of human-milk-fed infants [1] have a high potential to foster the early microbiome development [2]. Thus, they might prevent dysbiosis-associated complications such as necrotizing enterocolitis (NEC) and sepsis [3,4]. Numerous studies on the therapeutic effects of probiotics in preterm infants have been performed [4].…”

“…Thus, they might prevent dysbiosis-associated complications such as necrotizing enterocolitis (NEC) and sepsis [3,4]. Numerous studies on the therapeutic effects of probiotics in preterm infants have been performed [4]. However, the results remain inconclusive due to a high variability in study protocols, target populations and endpoints, probiotic formulations (e.g., strain composition and inclusion of single vs. multiple strains), and the context of nutrition [5].…”

gapseq: Informed prediction of bacterial metabolic pathways and reconstruction of accurate metabolic models

“…While single organisms can be considered as the building blocks of microbial communities, individual metabolic models of organisms are the building blocks of in silico microbial community simulations. Therefore, genome-scale metabolic models are increasingly applied to predict the function of multi-species microbial communities [31,43,51]. To correctly infer metabolic interaction networks between different organisms, it is important that individual models accurately predict nutrient utilisation (e.g.…”