We sought to identify the fungi that colonize healthy GI tracts and that have a sustained influence on the diverse functions of the gut microbiome. Instead, we found that all fungi in the stool of healthy volunteers could be explained by their presence in oral and dietary sources and that our results, together with those from other analyses, support the model that there is little or no gastrointestinal colonization by fungi. This may be due to Westernization, primate evolution, fungal ecology, and/or the strong defenses of a healthy immune system. Importantly, fungal colonization of the GI tract may often be indicative of disease. As fungi can cause serious infections in immunocompromised individuals and are found at increased abundance in multiple disorders of the GI tract, understanding normal fungal colonization is essential for proper treatment and prevention of fungal pathogenesis.

BackgroundLate onset sepsis (LOS) in preterm infants is associated with considerable morbidity and mortality. While studies have implicated gut bacteria in the aetiology of the disease, functional analysis and mechanistic insights are generally lacking. We performed temporal bacterial (n = 613) and metabolomic (n = 63) profiling on extensively sampled stool from 7 infants with LOS and 28 matched healthy (no LOS or NEC) controls.ResultsThe bacteria isolated in diagnostic blood culture usually corresponded to the dominant bacterial genera in the gut microbiome. Longitudinal changes were monitored based on preterm gut community types (PGCTs), where control infants had an increased number of PGCTs compared to LOS infants (P = 0.011). PGCT 6, characterised by Bifidobacteria dominance, was only present in control infants. Metabolite profiles differed between LOS and control infants at diagnosis and 7 days later, but not 7 days prior to diagnosis. Bifidobacteria was positively correlated with control metabolites, including raffinose, sucrose, and acetic acid.ConclusionsUsing multi-omic analysis, we show that the gut microbiome is involved in the pathogenesis of LOS. While the causative agent of LOS varies, it is usually abundant in the gut. Bifidobacteria dominance was associated with control infants, and the presence of this organism may directly protect, or act as a marker for protection, against gut epithelial translocation. While the metabolomic data is preliminary, the findings support that gut development and protection in preterm infants is associated with increased in prebiotic oligosaccharides (e.g. raffinose) and the growth of beneficial bacteria (e.g. Bifidobacterium).Electronic supplementary materialThe online version of this article (doi:10.1186/s40168-017-0295-1) contains supplementary material, which is available to authorized users.

Background and aims: Bacteriotherapy aimed at addressing dysbiosis may be therapeutic for Inflammatory Bowel Diseases (IBDs). We sought to determine if defined Bacteroides-based bacteriotherapy could be an effective and consistent alternative to fecal microbiota transplantation (FMT) in a murine model of IBD. Methods: We induced experimental colitis in 8-12-week-old C57BL/6 mice using 2-3% dextran sodium sulfate. Mice were simultaneously treated by oral gavage with a triple-Bacteroides cocktail, individual Bacteroides strains, FMT using stool from healthy donor mice, or their own stool as a control. Survival, weight loss and markers of inflammation (histology, serum amyloid A, cytokine production) were correlated to 16S rRNA gene profiling of fecal and mucosal microbiomes. Results: Triple-Bacteroides combination therapy was more protective against weight loss and mortality than traditional FMT therapy. B. ovatus ATCC8483 was more effective than any individual strain, or a combination of strains, in preventing weight loss, decreasing histological damage, dampening inflammatory response, and stimulating epithelial recovery. Irrespective of the treatment group, overall Bacteroides abundance associated with treatment success and decreased cytokine production while the presence of Akkermansia correlated with treatment failure. However, the therapeutic benefit associated with high Bacteroides abundance was negated in the presence of Streptococcus. Conclusions: Bacteroides ovatus monotherapy was more consistent and effective than traditional FMT at ameliorating colitis and stimulating epithelial recovery in a murine model of IBD. Given the tolerability of Bacteroides ovatus ATCC 8483 in an active, ongoing human study, this therapy may be repurposed for the management of IBD in a clinically expedient timeline.

The incidence of pediatric Inflammatory Bowel Disease, which includes Crohn's and ulcerative colitis, has risen alarmingly in the Western and developing world in recent decades. Epidemiological (including monozygotic twin and migrant) studies highlight the substantial role of environment and nutrition in IBD etiology. Here we review the literature supporting the developmental and environmental origins hypothesis of IBD. We also provide a detailed exploration of how the human microbiome and epigenome (primarily through DNA methylation) may be important elements in the developmental origins of IBD in both children and adults.