High individuality, large complexity and limited understanding of the mechanisms underlying human intestinal microbiome function remain the major challenges for designing beneficial modulation strategies. Exemplified by the analysis of intestinal bacteria in a thousand Western adults, we discuss key concepts of the human intestinal microbiome landscape, i.e. the compositional and functional 'core', the presence of community types and the existence of alternative stable states. Genomic investigation of core taxa revealed functional redundancy, which is expected to stabilize the ecosystem, as well as taxa with specialized functions that have the potential to shape the microbiome landscape. The contrast between Prevotella-and Bacteroides-dominated systems has been well described. However, less known is the effect of not so abundant bacteria, for example, Dialister spp. that have been proposed to exhibit distinct bistable dynamics. Studies employing time-series analysis have highlighted the dynamical variation in the microbiome landscape with and without the effect of defined perturbations, such as the use of antibiotics or dietary changes. We incorporate ecosystem-level observations of the human intestinal microbiota and its keystone species to suggest avenues for designing microbiome modulation strategies to improve host health.

Background: Faecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (rCDI). It restores the disrupted intestinal microbiota and subsequently suppresses C. difficile. The long-term stability of the intestinal microbiota and the recovery of mucosal microbiota, both of which have not been previously studied, are assessed herein. Further, the specific bacteria behind the treatment efficacy are also investigated. Methods: We performed a high-throughput microbiota profiling using a phylogenetic microarray analysis of 131 faecal and mucosal samples from 14 rCDI patients pre- and post-FMT during a 1-year follow-up and 23 samples from the three universal donors over the same period. Results: The FMT treatment was successful in all patients. FMT reverted the patients' bacterial community to become dominated by Clostridium clusters IV and XIVa, the major anaerobic bacterial groups of the healthy gut. In the mucosa, the amount of facultative anaerobes decreased, whereas Bacteroidetes increased. Post-FMT, the patients' microbiota profiles were more similar to their own donors than what is generally observed for unrelated subjects and this striking similarity was retained throughout the 1-year follow-up. Furthermore, the universal donor approach allowed us to identify bacteria commonly established in all CDI patients and revealed a commonly acquired core microbiota consisting of 24 bacterial taxa. Conclusions: FMT induces profound microbiota changes, therefore explaining the high clinical efficacy for rCDI. The identification of commonly acquired bacteria could lead to effective bacteriotherapeutic formulations. FMT can affect microbiota in the long-term and offers a means to modify it relatively permanently for the treatment of microbiota-associated diseases.

Rotavirus (RV) is the leading cause of diarrhea-related death in children worldwide and ninety-five percent of rotavirus deaths occur in Africa and Asia. Rotavirus vaccines (RVV) can dramatically reduce RV deaths, but have low efficacy in low-income settings where they are most needed. The intestinal microbiome may contribute to this decreased RVV efficacy. This pilot study hypothesizes that infants' intestinal microbiota composition correlates with RVV immune responses and that RVV responders have different gut microbiota as compared to non-responders. We conducted a nested, matched case-control study comparing the pre-vaccination intestinal microbiota composition between 10 6-week old Pakistani RVV-responders, 10 6-week old Pakistani RVV non-responders, and 10 healthy Dutch infants. RVV response was defined as an Immunoglobulin A of >= 20 IU/mL following Rotarix (TM)(RV1) vaccination in an infant with aprevaccination IgA RV1 response correlated with a higher relative abundance of bacteria belonging to Clostridium cluster XI and Proteobacteria, including bacteria related to Serratia and Escherichia coli. Remarkably, abundance of these Proteobacteria was also significantly higher in Dutch infants when compared to RV1-non-responders in Pakistan. This small but carefully matched study showed the intestinal microbiota composition to correlate with RV1 seroconversion in Pakistan infants, identifying signatures shared with healthy Dutch infants.

OBJECTIVES: Fecal microbiota transfer (FMT) is suggested as a potential treatment for patients with irritable bowel syndrome (IBS). We aimed to study the effect of allogenic and autologous FMT on IBS symptoms, visceral sensitivity, and compositional changes in fecal and mucosa-adherent microbiota. METHODS: Seventeen patients with IBS were randomized either to receive fecal material from a healthy donor (allogenic) or to receive their own fecal material (autologous). The fecal material was administered into the cecum by whole colonoscopy after bowel cleansing. RESULTS: No significant differences were found between the allogenic and the autologous FMT regarding symptom scores. However, symptom scores of patients receiving allogenic fecal material significantly decreased after FMT compared with baseline (P = 0.02), which was not the case in the autologous group (P=0.16). Visceral sensitivity was not affected except for a small beneficial effect on urge scores in the autologous group (P <0.05). While both fecal and mucosa-adherent microbiota of some patients shifted to their respective donor's fecal microbiota, some patients showed no relevant microbial changes after allogenic FMT. Large compositional shifts in fecal and mucosa-adherent microbiota also occurred in the autologous group. CONCLUSIONS: This study showed that a single FMT by colonoscopy may have beneficial effects in IBS; however, the allogenic fecal material was not superior to the autologous fecal material. This suggests that bowel cleansing prior to the colonoscopy and/or processing of the fecal material as part of the FMT routine contribute to symptoms and gut microbiota composition changes in IBS.