Long-term evolution and short-term adaptation of microbiota strains and sub-strains in mice

Metabolic reconstitution by a gnotobiotic microbiota varies over the circadian cycle

“…A widely used example, the OligoMM12, is a gnotobiotic consortium of 12 cultivable mouse-derived strains representing the major five bacterial phyla in the murine gut (Brugiroux et al, 2016). It is reproducible between facilities (Eberl et al, 2020) and extensive data now exists on the metabolism of individual species and their interactions with each other and the host (Streidl et al, 2021;Weiss et al, 2021;Wotzka et al, 2019;Yilmaz et al, 2021). However, working with these mice involves hygiene conditions similar to those required to work with germfree mice, which poses a technical challenge for the long-term analysis of mouse metabolism.…”

PD-1 checkpoint blockade disrupts CD4 T cell regulated adaptive B cell tolerance to foreign antigens

“…We do see smaller, more variable changes to IgA GC in the Peyer's Patch with small but significant increases in IgA PC in the bone marrow (but not spleen or PP) after acute PD-1 blockade, however the impact on the local PP IgA GC program remains uncharacterized. While IgA is more typically considered the humoral regulator of the microbiome (Donaldson et al, 2018;Fagarasan et al, 2010;Guzman-Bautista et al, 2020;Huus et al, 2021), anti-microbial IgG also impacts gut microbial composition (Chen et al, 2020; Macpherson et al, 2018;Slack et al, 2009;Yilmaz et al, 2021).…”

“…These TFH cells induce antibody class switch upon antigenactivation and promote affinity maturation within GC B cells to support long-term immune protection against a multitude of foreign antigens (McHeyzer-Williams et al, 2012;Mesin et al, 2016;Roco et al, 2019;Victora et al, 2010;Vinuesa et al, 2016). During development, some aspects of these CD4-regulated B cell compartments must also become tolerate to commensal organisms and a broad array of benign environmental antigens (Donaldson et al, 2018;Li et al, 2020;Morais et al, 2021;Yilmaz et al, 2021). Immune checkpoints regulate the quality and magnitude of CD4 T cell mediated signals that ultimately dictate B cell fate and impact immune function (ElTanbouly and Noelle, 2021;Liu et al, 2021;Qi, 2016;Sharpe and Pauken, 2018;Shi et al, 2018;Tan et al, 2021).…”

A standardized gnotobiotic mouse model harboring a minimal 15-member mouse gut microbiota recapitulates SOPF/SPF phenotypes

“…Importantly, the reduced microbial complexity of the GM15 community, the efficacy of its transfer to GF animals in different facilities, the tractability of its members and the control offered to the scientist on its composition over time allow easy quantification and recording of short and/or long-term gut microbiota dynamics, a current limit when using SPF/SOPF animals. Importantly, it was recently exemplified that minimal microbial communities do naturally evolve in gnotobiotic animals bred on chow diet or upon dietary challenges [28]. In order to ensure optimal reproducibility of preclinical works, it is advisable to regularly re-establish the models using fresh frozen bacterial samples and new GF animals to avoid drift and/or selection of variants in the microbial community.…”

“…It is a minimal microbiota gnotobiotic model composed of 12 defined cultivable mouse commensal bacteria from the miBC collection representing members of the major bacterial phyla of the mouse gut [19,25,26]. The community is transmissible and stable over consecutive mouse generations and animal facilities [27] and was recently used to reveal that the intestinal microbiota adapts to environmental changes by short-term effects of transcriptional reprogramming and adjustments in sub-strains proportions and long-term genomic positive selection [28]. Functionally, and unlike ASF, Oligo-MM 12 offers colonization resistance against Salmonella enterica serovar Typhimurium when supplemented with facultative anaerobic bacteria including Escherichia coli [22].…”