Dissecting the respective roles of microbiota and host genetics in the susceptibility of Card9-/- mice to colitis.

BACKGROUND: The etiology of inflammatory bowel disease (IBD) is unclear but involves both genetics and environmental factors, including the gut microbiota. Indeed, exacerbated activation of the gastrointestinal immune system toward the gut microbiota occurs in genetically susceptible hosts and under the influence of the environment. For instance, a majority of IBD susceptibility loci lie within genes involved in immune responses, such as caspase recruitment domain member 9 (Card9). However, the relative impacts of genotype versus microbiota on colitis susceptibility in the context of CARD9 deficiency remain unknown. RESULTS: Card9 gene directly contributes to recovery from dextran sodium sulfate (DSS)-induced colitis by inducing the colonic expression of the cytokine IL-22 and the antimicrobial peptides Reg3ß and Reg3γ independently of the microbiota. On the other hand, Card9 is required for regulating the microbiota capacity to produce AhR ligands, which leads to the production of IL-22 in the colon, promoting recovery after colitis. In addition, cross-fostering experiments showed that 5 weeks after weaning, the microbiota transmitted from the nursing mother before weaning had a stronger impact on the tryptophan metabolism of the pups than the pups' own genotype. CONCLUSIONS: These results show the role of CARD9 and its effector IL-22 in mediating recovery from DSS-induced colitis in both microbiota-independent and microbiota-dependent manners. Card9 genotype modulates the microbiota metabolic capacity to produce AhR ligands, but this effect can be overridden by the implantation of a WT or "healthy" microbiota before weaning. It highlights the importance of the weaning reaction occurring between the immune system and microbiota for host metabolism and immune functions throughout life. A better understanding of the impact of genetics on microbiota metabolism is key to developing efficient therapeutic strategies for patients suffering from complex inflammatory disorders. Video Abstract.

Ruminococcin A, a new lantibiotic produced by a Ruminococcus gnavus strain isolated from human feces.

When cultivated in the presence of trypsin, the Ruminococcus gnavus E1 strain, isolated from a human fecal sample, was able to produce an antibacterial substance that accumulated in the supernatant. This substance, called ruminococcin A, was purified to homogeneity by reverse-phase chromatography. It was shown to be a 2,675-Da bacteriocin harboring a lanthionine structure. The utilization of Edman degradation and tandem mass spectrometry techniques, followed by DNA sequencing of part of the structural gene, allowed the identification of 21 amino acid residues. Similarity to other bacteriocins present in sequence libraries strongly suggested that ruminococcin A belonged to class IIA of the lantibiotics. The purified ruminococcin A was active against various pathogenic clostridia and bacteria phylogenetically related to R. gnavus. This is the first report on the characterization of a bacteriocin produced by a strictly anaerobic bacterium from human fecal microbiota.

Relationship between intestinal colonization of Bifidobacterium bifidum in infants and the presence of exogenous and endogenous growth-promoting factors in their stools.

The relationship between the intestinal colonization of a test strain of Bifidobacterium bifidum requiring human milk growth-promoting factors in vitro and the presence of growth-promoting factors either in the stools of human neonates or in their diet was investigated. Thirty-one infants were inoculated with a single dose of this strain within the first 8 d of life. Spores of a strictly thermophilic Bacillus admixed with the B. bifidum inoculum were used as transit marker, and the fecal population levels of both strain B. bifidum and the transit marker were recorded within 6 d after inoculation. Strain B. bifidum was found in the predominant flora of six neonates. It was eliminated more quickly than the transit marker from the stools of 17 neonates. Its population remained at a low level in the remaining eight neonates. Amounts of B. bifidum growth-promoting factor in the infant stools were not significantly different whether they harbored strain B. bifidum at a high population level or not. Although these amounts were significantly higher in infants fed human milk containing B. bifidum growth-promoting factor than in infants fed formula milk without B. bifidum growth-promoting factor, strain B. bifidum became established in one of the 18 infants fed human milk and in five of the 13 formula-fed infants. No relationship could be found between the population levels of strain B. bifidum and those of facultatively anaerobic streptococci and enterobacteria already present on d 0 and 1. These results clearly show that no relationship exists between the intestinal colonization of B. bifidum and the amounts of exogenous or endogenous growth-promoting factors found in stools.

Efficiency of various bacterial suspensions derived from cecal floras of conventional chickens in reducing the population level of Salmonella typhimurium in gnotobiotic mice and chicken intestines.

The antagonistic effect exerted towards Salmonella typhimurium by the flora issued from conventional chickens was studied in gnotobiotic animals. In germfree chickens and mice inoculated with S. typhimurium, the highest bacterial counts were observed in ceca, and were not significantly different in either host. The protection afforded by the inoculation of cecal flora issued from a conventional chicken was more effective when this flora was inoculated first into germfree chickens than when it was given only after inoculation with S. typhimurium. Administration of a cecal flora from a 15-day-old chick to gnotobiotic mice and chicken resulted in the inhibition of a further intestinal colonization by S. typhimurium in both hosts. Sixteen strains were isolated among the predominant populations of the fecal flora from chicken flora recipient mice. Association of 14 strains of strictly anaerobic bacteria with 2 strains of Escherichia coli and Streptococcus faecium only decreased the number of S. typhimurium in the ileum of gnotobiotic mice, but not in their cecum. Anaerobe cultures were obtained from 10(-6) and 10(-8) dilutions prepared from the fecal flora of gnotobiotic recipient mice. Antagonistic bacteria were present only in cultures from the 10(-6) dilution. Cecal concentrations of volatile fatty acids were shown not to be the sole factor implicated in the antagonistic effect against S. typhimurium.

[Seroanthropological studies of albino and melanoderm Bamiléké populations (Cameroon). ABO and Rhesus erythrocyte groups, hemoglobin S and taste sensitivity to phenylthiocarbamide]. / Etudes séroanthropologiques des populations albinos et mélanodermes bamilékés (Cameroun). Groupes érythrocytaires ABO et Rhésus, hémoglobine S et sensibilité gustative à la phénylthiocarbamide.

Human oculocutaneous albinism is a recessive autosomic hereditary disease with a prevalence of 1/8,500 in bamileke tribe (Cameroon). ABO and Rhesus red blood cell group repartition, presence of hemoglobin S, taste sensitivity for phenylthiocarbamid in a group of 100 albino bamileke subjects were compared with these of 100 black bamileke subjects. There is no significant difference for these genetic markers mentionned above between albino and black bamileke subjects.

[Pathogenicity of various toxinogenic types of Clostridium perfringens administered by mouth to axenic and holoxenic mice]. / Pouvoir pathogène de différents types toxinogènes de Clostridium perfringens inoculés per os à des souris axéniques et holoxéniques.

Axenic mice died with signs of enterotoxaemia after oral ingestion of Clostridium perfringens type C or D. Under the same conditions, C. perfringens type B was less pathogenic, and types A and E showed no pathogenicity. The microflora of conventional mice prevented the establishment of C. perfringens types B, C and D in the digestive tract and protected them against the pathogenicity of these strains. Toxins produced in the caecum of monoxenic mice harbouring C. perfringens type C were not neutralized by the anti-C. perfringens type C antiserum. This suggests that the toxins produced in vivo by this strain were different from those produced in vitro.

[Antagonistic effect against "Clostridium perfringens" exerted in the digestive tract of gnotobiotic mice by "Clostridium" strains isolated from the microflora of conventional mice (author's transl)]. / Effet antagoniste à l'égard de Clostridium perfringens exercé par des souches de Clostridium isolées de la microflore de souris holoxéniques dans le tube digestif de souris gonotoxéniques.

Bacterial strains isolated from the digestive tract of conventional mice produced a barrier effect against a strain of Clostridium perfringens type A (strain CP) in the gastrointestinal tract of gnotobiotic mice. This barrier effect was observed when mice, monoassociated with Escherichia coli K12, were inoculated with a mixed culture of fusiform-shaped clostridia. The collection of fusiforms (collection D) was obtained from a single colony chosen from among the 26 types studied. Collection D and E. coli K12 together exerted a barrier effect against all strains of C. perfringens type A tested. No effect was observed against a C. perfringens type C strain. The expression of the barrier effect depended on the order in which the strains were used to inoculate the mice. Thus strain CP was eliminated from the digestive tract when the mice had previously been associated with collection D and E. coli K12. If the mice were inoculated with strain CP first, however, the barrier effect was only partial. We have also been able to use two strains of clostridia (C1, C3) instead of E. coli K12 to produce a drastic barrier effect against strain CP. The order in which the strains were used to inoculate the mice did not, in this case, influence the production of a barrier effect. Three strains (Da, Db, Dc) isolated from collection D, produced only a partial barrier effect against strain CP in mice previously associated with E. coli K12. These results illustrate the difficulties encountered in determining the minimal number of bacterial strains involved in the production of a barrier effect.