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Background. Acute Graft-versus-Host Disease (aGvHD) is the main complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Gut microbiota composition has been shown to contribute to aGvHD, however, the specific composition of the intestinal ecosystem involved in the pathologic process at the time of aGvHD onset is not yet fully known. Methods. A relevant series of allo-HSCT microbiome data sets were combined and reanalyzed, with focus on species level changes in the microbiota, using state-of-the-art and in part proprietary 16S analysis routines. Results. Immunosuppressive conditioning was found to impact gut microbiome (GM) composition. GM composition was found highly correlated with aGvHD status at onset (R2=0.4). The species diversity, average biological safety level (BSL), gram staining balance and the strict anaerobe proportion at aGvHD onset indicate that a moderate level of gram positive strict anaerobe cleansing with antibiotics reduces the risk of aGvHD. Butyrate producers were found associated with non-aGvHD controls, as well as the probiotic species and IL-10 inducer Bifidobacterium longum. Among species associated with mortality and aGvHD, we found Th1 and Th17 eliciting bacteria. We formulated a probiotic composition putatively competing with mortality and aGvHD species, from correlation analysis in a large superset of gut samples (n=17,800) from clinical- and crowd-sourced studies. Implications. To restore the Treg/Th17 balance, probiotic supplementation with B. longum eventually combined with Bacillus clausii, prebiotics and vitamin B9 is a treatment option. Simultaneous use of vancomycin, metronidazole, ceftazidime and rifaximin for GM control is a possibility, because of antibiotic resistance of B. longum.

Background: Inflammatory bowel disease (IBD) is a set of conditions characterized by non-infectious chronic inflammation of the gastrointestinal tract. These primarily include Crohns disease (CD), ulcerative colitis (UC) and indeterminate colitis. Fecal microbiota transplantation (FMT) has proven to be an effective treatment for some patients with active UC. However, factors contributing to the individual response to FMT therapy remain to be uncovered. There is currently no procedure allowing to predict the patients response and to select the most adequate donor(s). Methods: The first available UC FMT microbiome data sets were reanalyzed, with focus on species level changes in the microbiota, using state-of-the-art and in part proprietary 16S analysis routines. Results: We found the microbiomes of UC and CD patients to have paucity of obligate anaerobes, which could be a consequence of oxidative stress. Microbiomes of UC FMT responders and responder donors have higher phylogenetic diversity and a higher proportion of aerobes and facultative anaerobes as compared to non-responders and non-responder donors. We found Proteobacteria to account for the major part of species found in increased relative abundance in responders. Sphingolipid producers were found among these species. Implications: Our findings contribute to the establishment of selection criteria for UC FMT donor samples and composition guidelines for future synthetic microbial communities. Instead of replenishing missing obligate anaerobes, our results suggest that oxidative stress resistant Proteobacteria are important for successful UC FMT therapy.

International audience; Taking advantage of recent technology developments of 454 pyrosequencing we have undertaken whole genome sequencing of O. oeni strain IOEB 8413. This strain performs malolactic fermentation, but has a relatively low level of adaptation to oenological environment. The genome draft was obtained with Genome Sequencer FLX System (Roche). The generated 111 Mb of raw data (406 255 individual reads) was processed with Newbler Assembler through two different modes. The assembly resulting from the "de novo" mode consisted of 39 major contigs attaining an average 50x coverage. Manual draft inspection revealed that, independently of the number of contigs, it contained only 19 real gaps. Cumulated size of missing fractions was estimated to be less than 10 kb, thus allowing us one-step finishing by Sanger sequencing. For the second assembly mode, particularly indicated for resequencing projects, we have used as a reference the recently achieved genome of strain ATCC BAA-1163 (LAB9, communication Bon et al.). The 1,8-Mb chromosome is covered by 90% of all mapped reads, whereas the fully covered 3,9-kb high-copy plasmid monopolizes the remaining 10%. More than 97% of all reads were fully mapped to the reference (chromosome or plasmid) and organized in 18 "mapping" contigs. Less than 2% of reads aligned partially at the oriC linearization site or corresponded to repeat regions (rRNA operons). Only 429 reads are unique meaning that both strains have very close nucleotide content. Preliminary evaluation of the two genomes indicates no significant large-scale rearrangements. Functional annotation as well as further comparative analyses between available strains (including PSU-1) will await completion of the strain IOEB 8413 genome.

Bacterial consortium; Gut microbiome; Portal hypertension Consorcio bacteriano; Microbioma intestinal; Hipertensión portal Consorci bacterià; Microbioma intestinal; Hipertensió portal The gut microbiome has a recognized role in Non-alcoholic fatty liver disease (NAFLD) and associated comorbidities such as Type-2 diabetes and obesity. Stool transplantation has been shown to improve disease by restoring endothelial function and insulin signaling. However, more patient-friendly treatments are required. The present study aimed to test the effect of a defined bacterial consortium of nine gut commensal strains in two in vivo rodent models of Non-alcoholic steatohepatitis (NASH): a rat model of NASH and portal hypertension (PHT), and the Stelic animal (mouse) model (STAM™). In both studies the consortium was administered orally q.d. after disease induction. In the NASH rats, the consortium was administered for 2 weeks and compared to stool transplant. In the STAM™ study administration was performed for 4 weeks, and the effects compared to vehicle or Telmisartan at the stage of NASH/early fibrosis. A second group of animals was followed for another 3 weeks to assess later-stage fibrosis. In the NASH rats, an improvement in PHT and endothelial function was observed. Gut microbial compositional changes also revealed that the consortium achieved a more defined and richer replacement of the gut microbiome than stool transplantation. Moreover, liver transcriptomics suggested a beneficial modulation of pro-fibrogenic pathways. An improvement in liver fibrosis was then confirmed in the STAM™ study. In this study, the bacterial consortium improved the NAFLD activity score, consistent with a decrease in steatosis and ballooning. Serum cytokeratin-18 levels were also reduced. Therefore, administration of a specific bacterial consortium of defined composition can ameliorate NASH, PHT, and fibrosis, and delay disease progression.