Adaptive immunity increases the pace and predictability of evolutionary change in commensal gut bacteria

Abstract

Co-evolution between the mammalian immune system and the gut microbiota is believed to have shaped the microbiota's astonishing diversity. Here we test the corollary hypothesis that the adaptive immune system, directly or indirectly, influences the evolution of commensal species. We compare the evolution of Escherichia coli upon colonization of the gut of wild-type and Rag2−/− mice, which lack lymphocytes. We show that bacterial adaptation is slower in immune-compromised animals, a phenomenon explained by differences in the action of natural selection within each host. Emerging mutations exhibit strong beneficial effects in healthy hosts but substantial antagonistic pleiotropy in immune-deficient mice. This feature is due to changes in the composition of the gut microbiota, which differs according to the immune status of the host. Our results indicate that the adaptive immune system influences the tempo and predictability of E. coli adaptation to the mouse gut.

A Mutational Hotspot and Strong Selection Contribute to the Order of Mutations Selected for during Escherichia coli Adaptation to the Gut

“…We note that despite the allelic variation within each target of adaptation, only one allele representative of each locus was tested. While for the gat locus we have previously shown that different alleles have equivalent selective effects [8,27], we acknowledge that for the second targets of adaptation, different alleles may have different phenotypes.…”

The evolution of the host microbiome as an ecosystem on a leash

“…Genotype discrimination can be limited by an inability to detect a beneficial strain that evolves a pathogenic phenotype, or vice versa. The adaptive immune system can solve this problem by learning new associations during infection—combining trait and genotypic information—and adaptive immunity can impact the microbiota 49,51 . However, it is not yet clear whether this results in effective control of the microbiota at epithelial surfaces.…”

“…We, therefore, expect natural selection to favour hosts that act as ecosystem engineers that influence not only individual species but also community-level properties, such as stability and productivity 14 . Possible mechanisms of this control include the immune system 49 and epithelial mucus secretion, which can weaken ecological interactions by regulating species density and increasing spatial structure 14 . Interrupting the immune system or mucus secretion 22,52 , therefore, may lead to a less stable, and thus less diverse, microbiota.…”

Gut microbiota utilize immunoglobulin A for mucosal colonization

“…However, not only do animals tolerate a complex microbiome, in the case of B. fragilis provoking an immune response paradoxically enables intimate association with its mammalian host. Related commensal bacteria may also benefit from actively engaging IgA during symbiosis, as Rag2 −/− mice devoid of adaptive immunity harbor fewer Bacteroides (43), and both B cell deficient and IgA −/− animals display decreased colonization by the Bacteroidaceae family (44). IgA has been previously shown to increase adherence of Escherichia coli (15), Bifidobacterium lactis, and Lactobacillus ramnosus (16) to tissue-cultured epithelial cells, suggesting that these microorganisms may also benefit from IgA to establish a mucosal bacterial community.…”