The laboratory worm Caenorhabditis elegans feeds on Escherichia coli its whole life, but in nature its diet consists of rotting plants rich in bacilli and lactic acid bacteria. One such bacterium, Lactococcus lactis JCM 5805, extends the worm's life by four days, while another, Lactiplantibacillus plantarum MAFF 401534, produces no such effect. Why? It turns out the secret is not that the bacterium activates the host's own defense programs, but that it does part of the work of maintaining the host's body itself. It's as if you hired a contractor who doesn't just advise you on how to reinforce the foundation, but actually delivers bricks and cement.
The researchers compared three diets for the nematodes: the standard OP50, Lc5805, and Lp1534. The worms were fed live or heat-killed bacteria, and then changes in gene expression and metabolite composition were measured at 10, 60, and 300 minutes. The main result: only live Lc5805 cells caused citrulline to accumulate in the worm's tissues, reaching 100 nmol/g within just 10 minutes of feeding, whereas in worms on OP50 or Lp1534 the level stayed below 10 nmol/g. Heat treatment of Lc5805 completely abolished both the citrulline accumulation and the lifespan extension.
Analysis of the bacterial cells showed that citrulline is present only in Lc5805, and that the arcA gene, responsible for converting arginine into citrulline, is actively expressed inside the worm's intestine. Transcriptome analysis revealed that in worms that ate Lc5805, 74 genes linked to cuticle formation were specifically activated, including 58 collagen genes. At the same time, the classic markers of stress resistance and longevity (sod-3, gst-4) were not switched on. This points to an unusual mechanism: the bacterium itself supplies the building blocks for collagen, sparing the host the need to launch energy-expensive defense programs.
This mechanism has been called "metabolic outsourcing": the host doesn't merely receive nutrients, it directly uses the enzymes and intermediate metabolites of the bacteria to maintain its own structures. This shifts the focus away from the traditional view of probiotics as immune modulators or vitamin suppliers. For gerontology, a new class of interventions is opening up, aimed not at the organism's own longevity genes but at its microbial partners.
The work explains why probiotic effects often fail to reproduce: what matters is not only the bacterial species but also its metabolic activity in a live state. The next step is to check whether a similar mechanism works in mammals, in particular in mice with deficiencies in urea cycle enzymes or with age-related decline in collagen synthesis. It may be possible to create synthetic bacterial consortia optimized to deliver specific amino acids or enzymes to the gut. The long-term prospect is the development of "living therapeutics" to maintain connective tissue health and slow aging in humans.
Citrulline got its name from the Latin citrullus, meaning watermelon, from which it was first isolated in 1914. In the paper, the citrulline concentration in worms that ate Lc5805 reached 100 nmol/g, comparable to the content of this amino acid in watermelon flesh.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.