Systematic evaluation of genome-wide metabolic landscapes in lactic acid bacteria reveals diet-induced and strain-specific probiotic idiosyncrasies

Abstract

Lactic acid bacteria (LAB) naturally occur in animal and plant niches and are well-known to elicit several health benefits in humans. Yet, how they adapt their functional metabolic landscapes to diverse nutrient environments and synthesize relevant bioactive compounds remain unexplored across genera, species and strains. Hence, presented herein is a systematic framework for comprehensively characterizing the genome-wide metabolisms of six representative LAB by combining multi-omics data with in silico modeling. We analyse the differences in their growth and cellular fitness, biosynthetic capability of health-relevant compounds, i.e., postbiotics, and probable interactions with 15 common gut microbiota under 11 virtual dietary regimes, and show such attributes are diet- and species-specific. Particularly, some LAB exhibit a desirable balance between synthesis of beneficial postbiotic compounds, positive interactions with beneficial gut commensals, and the ability to colonize and persist in gut environment. We also observe that high fat-low carb diets likely lead to detrimental outcomes in most LAB. Our results clearly highlight that probiotics are not one size fits all commodities and need to be formulated in a personalized manner for their use as dietary supplements and live biotherapeutics. Overall, the proposed framework will systematize the probiotic administration and could also widen the strain repertoire.

Systems Biology of Gut Microbiota-Human Receptor Interactions: Toward Anti-inflammatory Probiotics

“…Well-curated models can further provide quantitative estimates of the ligand production, which may serve as proxies for ligand-receptor activities. For instance, we have reconstructed and used GEMs for 18 lactic acid bacterial strains to systematically evaluate their probiotic capabilities ( Koduru et al, 2021 ). This study constitutes one of the first attempts to theoretically quantify the probiotic potential of strains.…”