טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentBuhnik Rosenblau Keren
SubjectThe Genetic Aspect of Host-Bacteria Interaction in the
Gut
DepartmentDepartment of Biotechnology and Food Engineering
Supervisor Professor Yechezkel Kashi
Full Thesis textFull thesis text - English Version


Abstract

The gut is a habitat for complex bacterial populations which are highly important for maintaining a healthy organism. The composition of the gut microbiota is host-specific and affected by environmental factors while the relative impact of the host’s genetics is recently uncovered. Here we study the effect of host’s genetics on the composition of intestinal lactic acid bacteria (LAB), a bacterial group which includes many health-promoting strains. Testing the composition of fecal LAB populations of 62 animal hosts revealed that the abundance of the E.faecium cluster and L.intestinalis was associated with specific host taxonomic groups. Furthermore, analyzing the fecal LAB population of two genetically different mouse lines (C57BL/6J and BALB/C) revealed highly reproducible variation between the lines. L.johnsonii, a potentially probiotic bacterium, appeared at significantly higher levels in C57BL/6J mouse feces. In the BALB/C gut, 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 relatively lower maternal effect. The adhesion ability of L.johnsonii to intestinal mucus from C57BL/6J and BALB/C mice was further tested, revealing elevated adhesion ability to the C57BL/6J mucus, which may partially explain L.johnsonii difference in fecal samples of the two mouse lines.

At the next stage, intestinal LAB species from various hosts were tested at the bacterial strain level. The patterns of the genetic relationships among L.johnsonii strains from various hosts inferred by different DNA fingerprinting methods revealed different clusters of L.johnsonii strains, each associated with strains from different host. This may be a result of co-evolution of the host and its gut microbiota. Strain typing conducted on a panel of strains belonging to E.faecalis revealed different results, with no association between the isolation origin of the strains and their phylogenetic relationship. 

Our findings indicate an association of particular LAB species and strains with the host taxonomy in general and further suggests a major effect of mouse genetic background on L.johnsonii gut persistence 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.