Predominant Effect of Host Genetics on Levels of Lactobacillus johnsonii Bacteria in the Mouse Gut

Abstract

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.

Quantitatively Different, yet Qualitatively Alike: A Meta-Analysis of the Mouse Core Gut Microbiome with a View towards the Human Gut Microbiome

“…The composition of the GM has previously been shown to be influenced by multiple factors including environment and host genetics [8], [27]–[31]. The latter seems to be a major force driving the GM differences between the various mice and human clusters.…”

Host genetic and environmental effects on mouse intestinal microbiota

“…Two such studies (Benson et al, 2010;Buhnik-Rosenblau et al, 2011) found ties between host genetics and Lactobacillus in mice. Another study (Alexander et al, 2006) in which mice from 23 inbred strains were inoculated with and tested for the altered Schaedler's flora using specific quantitative PCR assays noted significant differences for these species.…”

The human microbiota associated with overall health

“…If the genetic background does not match well, even the already released probiotics could not survive for an extended time. For example, based on 16S rRNA gene genotyping, Buhnik-Rosenblau et al (2011) found that L. johnsonii (a potentially probiotic bacterium) appeared at significantly higher levels in C57BL/6J versus BALB/c mouse feces, their offspring presented similar L. johnsonii levels. However, after oral administration, the L. johnsonii level decreased rapidly in the BALB/c gut, suggesting that some selective force does not allow its persistence at higher levels.…”