A phylogenomic analysis of Limosilactobacillus reuteri reveals ancient and stable evolutionary relationships with rodents and birds and zoonotic transmission to humans

Abstract

Background Gut microbes play crucial roles in the development and health of their animal hosts. However, the evolutionary relationships of gut microbes with vertebrate hosts, and the consequences that arise for the ecology and lifestyle of the microbes are still insufficiently understood. Specifically, the mechanisms by which strain-level diversity evolved, the degree by which lineages remain stably associated with hosts, and how their evolutionary history influences their ecological performance remain a critical gap in our understanding of vertebrate-microbe symbiosis. Results This study presents the characterization of an extended collection of strains of Limosilactobacillus reuteri and closely related species from a wide variety of hosts by phylogenomic and comparative genomic analyses combined with colonization experiments in mice to gain insight into the long-term evolutionary relationship of a bacterial symbiont with vertebrates. The phylogenetic analysis of L. reuteri revealed early-branching lineages that primarily consist of isolates from rodents (four lineages) and birds (one lineage), while lineages dominated by strains from herbivores, humans, pigs, and primates arose more recently and were less host specific. Strains from rodent lineages, despite their phylogenetic divergence, showed tight clustering in gene-content-based analyses. These L. reuteri strains but not those ones from non-rodent lineages efficiently colonize the forestomach epithelium of germ-free mice. The findings support a long-term evolutionary relationships of L. reuteri lineages with rodents and a stable host switch to birds. Associations of L. reuteri with other host species are likely more dynamic and transient. Interestingly, human isolates of L. reuteri cluster phylogenetically closely with strains from domesticated animals, such as chickens and herbivores, suggesting zoonotic transmissions. Conclusions Overall, this study demonstrates that the evolutionary relationship of a vertebrate gut symbiont can be stable in particular hosts over time scales that allow major adaptations and specialization, but also emphasizes the diversity of symbiont lifestyles even within a single bacterial species. For L. reuteri, symbiont lifestyles ranged from autochthonous, likely based on vertical transmission and stably aligned to rodents and birds over evolutionary time, to allochthonous possibly reliant on zoonotic transmission in humans. Such information contributes to our ability to use these microbes in microbial-based therapeutics.

Pangenome Analysis Reveals the Genetic Basis for Taxonomic Classification of the Lactobacillaceae Family

“…Only two species had more closed pangenomes, Lentilactobacillus parabuchneri, with a normalized λ value of 0.171 ± 0.004 and Lactobacillus acidophilus, with a normalized λ value of 0.077 ± 0.021. Limosilactobacillus reuteri had the most open pangenome (Li et al, 2023), with a normalized λ value of 0.378 ± 0.015, followed by Lactobacillus crispatus, with a normalized λ value of 0.364 ± 0.017. The genera with the most Fig.…”

Microbe Profile: The Lactobacillaceae

“…Overall, the findings are consistent with a model in which free-living ancestors evolved into increasingly host-adapted symbiotics, with present-day species displaying substantial variation in terms of the reliance on environmental niches and the degree of host and niche specificity [ 4 ]. On a finer scale, phylogenetic analysis performed for a limited number of species (such as Limosilactobacillus reuteri ) revealed distinct host adaptations and specialization at sub-species level [ 5 ]. The most specialized and strictly host adapted species among the Lactobacillaceae , as demonstrated by the smallest genomes (see graphical abstract), are found among the symbionts of insects, as well as in the vaginal species Lactobacillus iners .…”

Probiotic Properties of Lactobacillus Reuteri (L. Reuteri) Strains

“…Он принадлежит к роду Lactobacillus, который включает в себя многие другие грамположительные кислородоустойчивые ферментативные бактерии, такие как L. acidophilus, L. bulgaricus, L. casei и L. rhamnosus [7]. Lactobacillus reuteri DSM 17938, недавно переименованный в Limosilactobacillus reuteri (L. reuteri), является пробиотиком, хорошо идентифицированным по его благотворному влиянию на некоторые желудочно-кишечные заболевания [2,4,[8][9][10].…”

“…Пробиотический эффект L. reuteri обусловлен целым комплексом особенных свойств. Благодаря способности образовывать биопленки [4,11], колонии L. reuteri устойчивы к низким значениям рН и солям желчи [12]. Доказано, что L. reuteri способен прикрепляться к муцину, кишечному эпителию и к эпителиальным клеткам кишечника у ряда позвоночных [13].…”