Metabolic outsourcing from ingested lactic acid bacteria extends Caenorhabditis elegans healthspan via bacterial amino acid and enzyme provision

Abstract

Lactic acid bacteria promote longevity, yet the host-microbe metabolic mechanisms remain obscure. Using Caenorhabditis elegans, which lacks a urea cycle, we investigated how Lactococcus lactis JCM 5805 (Lc5805) extends lifespan. Live Lc5805 consumption upregulated 74 cuticle-formation genes, primarily collagens, supporting structural integrity for longevity without activating host stress responses. Multi-omics and UPLC-MS analyses revealed a dramatic accumulation of L-citrulline and L-ornithine, driven by high intestinal expression of bacterial arginine deiminase (arcA). The finding that heat-treated Lc5805 failed to induce citrulline accumulation and lifespan extension confirms that this metabolic outsourcing system, the operation of the arginine deiminase pathway, requires active metabolic and enzymatic activity by live bacteria in the gut. By utilizing bacterial metabolites and enzymes to fuel collagen maintenance, the host avoids endogenous energy expenditure. This study unveils a novel symbiotic paradigm of "Metabolic Outsourcing" governing organismal longevity.