Differences in the microbiome of the small intestine of Leghorn lines divergently selected for antibody titer to sheep erythrocytes suggest roles for commensals in host humoral response

Abstract

For forty generations, two lines of White Leghorn chickens have been selected for high (HAS) or low (LAS) antibody response to a low dose injection of sheep red blood cells (SRBCs). Their gut is home to billons of microorganisms and the largest number of immune cells in the body; therefore, the objective of this experiment was to gain understanding of the ways the microbiome may influence the differential antibody response observed in these lines. We achieved this by characterizing the small intestinal microbiome of HAS and LAS chickens, determining their functional microbiome profiles, and by using machine learning to identify microbes which best differentiate HAS from LAS and associating the abundance of those microbes with host gene expression. Microbiome sequencing revealed greater diversity in LAS but statistically higher abundance of several strains, particularly those of Lactobacillus, in HAS. Enrichment of microbial metabolites implicated in immune response such as lactic acid, short chain fatty acids, amino acids, and vitamins were different between HAS and LAS. The abundance of several microbial strains corresponds to enriched host gene expression pathways related to immune response. These data provide a compelling argument that the microbiome is both likely affected by host divergent genetic selection and that it exerts influence on host antibody response by various mechanisms.

Keywords: VA tech HAS and LAS; antibody response; immunogenetics; machine learning; microbiome.