The gut microbiota is a complex ecosystem, affected by both environmental factors and host genetics. Here, we aim at uncovering the bacterial taxa whose gut persistence is controlled by host genetic variation. We used a murine model based on inbred lines BALB/c and C57BL/6J and their F1 reciprocal hybrids (♀C57BL/6J × ♂BALB/c; ♀BALB/c × ♂C57BL/6J). To guarantee genetic similarity of F1 offspring, including the sex chromosomes, we used only female mice. Based on 16S rRNA gene sequencing, we found that the genetically different inbred lines present different microbiota, whereas their genetically identical F1 reciprocal hybrids presented similar microbiota. Moreover, the F1 microbial composition differed from that of both parental lines. Twelve taxa were shown to have genetically controlled gut persistence, while none were found to show maternal effects. Nine of these taxa were dominantly inherited by the C57BL/6J line. Cohousing of the parental inbred lines resulted in a temporary and minor shift in microbiota composition, which returned back to the former microbial composition following separation, indicating that each line tends to maintain a unique bacterial signature reflecting the line. Taken together, our findings indicate that mouse genetics has an effect on the microbial composition in the gut, which is greater than maternal effect and continuous exposure to different microbiota of the alternative line. Uncovering the bacterial taxa associated with host genetics and understanding their role in the gut ecosystem could lead to the development of genetically oriented probiotic products, as part of the personalized medicine approach. IMPORTANCE The gut microbiota play important roles for their host. The link between host genetics and their microbial composition has received increasing interest. Using a unique reciprocal cross model, generating genetically similar F1 hybrids with different maternal inoculation, we demonstrate the inheritance of gut persistence of 12 bacterial taxa. No taxa identified as maternally transmitted. Moreover, cohabitation of two genetically different inbred lines did not dramatically affect the microbiota composition. Taken together, our results demonstrate the importance of the genetic effect over maternal inoculation or effect of exposure to unlike exogenous microbiota. These findings may lead to the development of personalized probiotic products, specifically designed according to the genetic makeup.

The gut microbiota is strongly associated with the well-being of the host. Its composition is affected by environmental factors, such as food and maternal inoculation, while the relative impact of the host's genetics have been recently uncovered. Here, we studied the effect of the host genetic background on the composition of intestinal bacteria in a murine model, focusing on lactic acid bacteria (LAB) as an important group that includes many probiotic strains. Based on 16S rRNA gene genotyping, variation was observed in fecal LAB populations of BALB/c and C57BL/6J mouse lines. Lactobacillus johnsonii, a potentially probiotic bacterium, appeared at significantly higher levels in C57BL/6J versus BALB/c mouse feces. In the BALB/c gut, the L. johnsonii level decreased rapidly after oral administration, suggesting that some selective force does not allow its persistence at higher levels. The genetic inheritance of L. johnsonii levels was further tested in reciprocal crosses between the two mouse lines. The resultant F1 offspring presented similar L. johnsonii levels, confirming that mouse genetics plays a major role in determining these levels compared to the smaller maternal effect. Our findings suggest that mouse genetics has a major effect on the composition of the LAB population in general and on the persistence of L. johnsonii in the gut in particular. Concentrating on a narrow spectrum of culturable LAB enables the isolation and characterization of such potentially probiotic bacterial strains, which might be specifically oriented to the genetic background of the host as part of a personalized-medicine approach.

The composition of the gut microbiota is affected by environmental factors as well as host genetics. Iron is one of the important elements essential for bacterial growth, thus we hypothesized that changes in host iron homeostasis, may affect the luminal iron content of the gut and thereby the composition of intestinal bacteria. The iron regulatory protein 2 (Irp2) and one of the genes mutated in hereditary hemochromatosis Hfe , are both proteins involved in the regulation of systemic iron homeostasis. To test our hypothesis, fecal metal content and a selected spectrum of the fecal microbiota were analyzed from Hfe-/-, Irp2-/- and their wild type control mice. Elevated levels of iron as well as other minerals in feces of Irp2-/- mice compared to wild type and Hfe-/- mice were observed. Interestingly significant variation in the general fecal-bacterial population-patterns was observed between Irp2-/- and Hfe-/- mice. Furthermore the relative abundance of five species, mainly lactic acid bacteria, was significantly different among the mouse lines. Lactobacillus (L.) murinus and L. intestinalis were highly abundant in Irp2-/- mice, Enterococcus faecium species cluster and a species most similar to Olsenella were highly abundant in Hfe-/- mice and L. johnsonii was highly abundant in the wild type mice. These results suggest that deletion of iron metabolism genes in the mouse host affects the composition of its intestinal bacteria. Further studying the relationship between gut microbiota and genetic mutations affecting systemic iron metabolism in human should lead to clinical implications.

BackgroundThe intestinal microbiota, composed of complex bacterial populations, is host-specific and affected by environmental factors as well as host genetics. One important bacterial group is the lactic acid bacteria (LAB), which include many health-promoting strains. Here, we studied the genetic variation within a potentially probiotic LAB species, Lactobacillus johnsonii, isolated from various hosts.ResultsA wide survey of 104 fecal samples was carried out for the isolation of L. johnsonii. As part of the isolation procedure, terminal restriction fragment length polymorphism (tRFLP) was performed to identify L. johnsonii within a selected narrow spectrum of fecal LAB. The tRFLP results showed host specificity of two bacterial species, the Enterococcus faecium species cluster and Lactobacillus intestinalis, to different host taxonomic groups while the appearance of L. johnsonii and E. faecalis was not correlated with any taxonomic group. The survey ultimately resulted in the isolation of L. johnsonii from few host species. The genetic variation among the 47 L. johnsonii strains isolated from the various hosts was analyzed based on variation at simple sequence repeats (SSR) loci and multi-locus sequence typing (MLST) of conserved hypothetical genes. The genetic relationships among the strains inferred by each of the methods were similar, revealing three different clusters of L. johnsonii strains, each cluster consisting of strains from a different host, i.e. chickens, humans or mice.ConclusionsOur typing results support phylogenetic separation of L. johnsonii strains isolated from different animal hosts, suggesting specificity of L. johnsonii strains to their hosts. Taken together with the tRFLP results, that indicated the association of specific LAB species with the host taxonomy, our study supports co-evolution of the host and its intestinal lactic acid bacteria.

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