Functional insights on probiotics activity in the gut from metagenomic data

Abstract

Recently, a novel way was described for selection of antibiotic resistance genes in the microbiome of the gut, in which probiotic bacteria are involved. Classical, direct selection of resistance against a particular antibiotic is straightforward, and this can be accompanied by cross-resistance, when one resistant mechanism applies to more than one antimicrobial. Co-selection occurs when multiple antibiotic resistance genes (ARGs) are simultaneously transferred between bacteria in a single transfer event. To these three selection mechanisms that result in antimicrobial resistance, we can now add a fourth mechanism. It was shown that propagation of bacteria that carried ARGs had occurred in volunteers who had first been treated with a combination of antibiotics (ciprofloxacin and metronidazole) and then took a cocktail of probiotic bacteria (Bio-25, Ambrosia SupHerb Ltd., Netanya, Israël -containing 11 different species) (Montassier et al., 2021). In a small number of individuals, this resulted in proliferation of certain bacterial species in their gut that carried vancomycin resistance genes. The authors showed that these vancomycin resistance genes did not stem from the probiotic bacteria that had been administered. Whether these genes resulted in overt vancomycin resistance was not assessed, but the observations identify a novel mechanism by which ARGs can be enriched in a microbiome: the sequential application of antibiotics and probiotics. Importantly, and a bit worrisome, the selected ARGs were not active against the applied antibiotics. The authors warn for this unwanted effect of probiotics (Montassier et al., 2021). Do these observations actually pose a reason for concern? Or do they describe an important mechanism how probiotics can exert their beneficial health effects? The data indicate that their presence in the gut can result in a shift in commensal bacterial populations, resulting in expansion of species that are beneficial to the host.The described enrichment of ARG-carrying bacteria was observed following metagenomic sequencing of endoscopic samples. The effect was only seen in individuals who the authors described as 'permissive' , meaning the probiotic bacteria colonised their gut. The effect was only observed in the microbiome of their lower gastrointestinal tract, and only in lumen samples but not in mucosal endoscopic samples or in faeces. The effect was not observed in individuals who the authors described as 'resistant' , meaning the probiotic bacteria didn't multiply in their gut. Following the treatment, the 'permissive' individuals had larger numbers of AGR-carrying Blautia species and Clostridium species (Clostridium citroniae, Clostridium leptum) in their gut, and by the use of mouse experiments it was confirmed that Blautia coccoides, Blautia hominis and Blautia producta had all increased as a result of the sequential antibiotic and probiotic treatment (Montassier et al., 2021).The beneficial effects of these species, and conversely, correlations between their absence or lower abundanc...