'Inside Out'– a dialogue between mitochondria and bacteria.

Mitochondria play crucial roles in regulating metabolism and longevity. A body of recent evidences reveals that the gut microbiome can also exert significant effects on these activities in the host. Here, by summarizing the currently known mechanisms underlying these regulations, and by comparing mitochondrial fission–fusion dynamics with bacterial interactions such as quorum sensing, we hypothesize that the microbiome impacts the host by communicating with their intracellular relatives, mitochondria. We highlight recent discoveries supporting this model, and these new findings reveal that metabolite molecules derived from bacteria can fine‐tune mitochondrial dynamics in intestinal cells and hence influence host metabolic fitness and longevity. This perspective mode of chemical communication between bacteria and mitochondria may help us understand complex and dynamic environment–microbiome–host interactions regarding their vital impacts on health and diseases. Gut microbiome orchestrates biological processes in the host by communicating with mitochondria, intracellular organelles that originated from bacteria. Reciprocating to environmental challenges, bacteria produce metabolites that can modulate mitochondrial dynamics to adjust intracellular activities. Together, the interplay between microbiome and mitochondria provides new insights into the regulation of host metabolic health and longevity. [ABSTRACT FROM AUTHOR]