Shifting from Abundance and Centrality-Fluctuating Microbes are Key Drivers of Long Lasting Microbiome Manipulation

The gut microbiome can be altered in ways that impact both microbial composition and host health. Various interventions, including prebiotics, probiotics, postbiotics, and fecal microbiota transplants (FMT), can influence this balance. However, most interventions cannot create lasting changes in the microbiome. We propose that certain microbes, denoted here as Regime Shifting Microbes (RSM), have the unique ability to induce durable shifts in the microbiome that may also affect the host’s phenotype. Two main ideas have been suggested to define RSMs: they are either highly abundant microbes or central players in the microbial interaction network. However, a combination of extensive microbial sequencing, data on probiotic persistence, and ecological modeling, indicates otherwise. Instead, we find that microbes with a high degree of variability across individuals and over time—termed “fluctuating”—are most likely to drive sustained changes in microbial composition. To confirm this, we evaluated the impact of these fluctuating microbes under various conditions and across individuals, using multiple metrics for regime shifts, including overall microbial abundance shifts, colonization likelihood, persistence, and effects on host phenotype. In summary, we propose that for microbes to be effective candidates as next-generation probiotics, they should exhibit variability over time and across individuals.