Complex gene-environment interactions are considered important in the development of obesity. The composition of the gut microbiota can determine the efficacy of energy harvest from food and changes in dietary composition have been associated with changes in the composition of gut microbial populations. The capacity to explore microbiota composition was markedly improved by the development of metagenomic approaches, which have already allowed production of the first human gut microbial gene catalogue and stratifying individuals by their gut genomic profile into different enterotypes, but the analyses were carried out mainly in non-intervention settings. To investigate the temporal relationships between food intake, gut microbiota and metabolic and inflammatory phenotypes, we conducted diet-induced weight-loss and weight-stabilization interventions in a study sample of 38 obese and 11 overweight individuals. Here we report that individuals with reduced microbial gene richness (40%) present more pronounced dys-metabolism and low-grade inflammation, as observed concomitantly in the accompanying paper. Dietary intervention improves low gene richness and clinical phenotypes, but seems to be less efficient for inflammation variables in individuals with lower gene richness. Low gene richness may therefore have predictive potential for the efficacy of intervention.

Clostridium difficile is a major enteric pathogen responsible for antibiotic-associated diarrhea. Host susceptibility to C. difficile infections results partly from inability of the intestinal microbiota to resist C. difficile colonization. During early infancy, asymptomatic colonization by C. difficile is common and the intestinal microbiota shows low complexity. Thus, we investigated the potential relationship between the microbiota composition and the implantation of C. difficile in infant gut. Fecal samples from 53 infants, ages 0 to 13 months, 27 negative and 26 positive for C. difficile, were studied. Dominant microbiota profiles were assessed by PCR-temporal temperature gradient gel electrophoresis (TTGE). Bacterial signatures of the intestinal microbiota associated with colonization by C. difficile were deciphered using principal component analysis (PCA). Resulting bands of interest in TTGE profiles were excised, sequenced, and analyzed by nucleotide BLAST (NCBI). While global biodiversity was not affected, interclass PCA on instrumental variables highlighted significant differences in dominant bacterial species between C. difficile-colonized and noncolonized infants (P ‫؍‬ 0.017). Four bands were specifically associated with the presence or absence of C. difficile: 16S rRNA gene sequences related to Ruminococcus gnavus and Klebsiella pneumoniae for colonized infants and to Bifidobacterium longum for noncolonized infants. We demonstrated that the presence of C. difficile in the intestinal microbiota of infants was associated with changes in this ecosystem's composition. These results suggest that the composition of the gut microbiota might be crucial in the colonization process, although the chronology of events remains to be determined.

The human gastrointestinal (GI) tract is the habitat for hundreds of microbial species, of which many cannot be cultivated readily, presumably because of the dependencies between species. Studies of microbial co-occurrence in the gut have indicated community substructures that may reflect functional and metabolic interactions between cohabiting species. To move beyond species co-occurrence networks, we systematically identified transcriptional interactions between pairs of coexisting gut microbes using metagenomics and microarray-based metatranscriptomics data from 233 stool samples from Europeans. In 102 significantly interacting species pairs, the transcriptional changes led to a reduced expression of orthologous functions between the coexisting species. Specific species-species transcriptional interactions were enriched for functions important for H and CO homeostasis, butyrate biosynthesis, ATP-binding cassette (ABC) transporters, flagella assembly and bacterial chemotaxis, as well as for the metabolism of carbohydrates, amino acids and cofactors. The analysis gives the first insight into the microbial community-wide transcriptional interactions, and suggests that the regulation of gene expression plays an important role in species adaptation to coexistence and that niche segregation takes place at the transcriptional level.