Gut bacteria make fats that feed liver and muscle mitochondria — in mice

Edited by Samael A. Tejada, Founder & Editor-in-Chief

The microbiome story usually stops at inflammation. This one follows two bacterial fats out of the gut, through blood and lymph, and into the mitochondria of liver and muscle — and finds the power plants running better when the fats arrive, and worse when they are taken away.

What did the liver study find?

Christopher Blesso's UConn team had expected the opposite: bacterial lipids are usually pro-inflammatory, and in 2022 the group showed these glycine lipids acted as immunosuppressive signals in atherosclerosis and liver inflammation. For the new work, mice were fed a high-fat, high-sugar Western diet to induce MASLD progression, then given one-microgram injections of L654 or L1256 every other day for eight weeks. Both lipids significantly attenuated disease severity on histopathology, and gene-regulation analysis found enhancement of genes controlling mitochondrial biogenesis and fat oxidation. The depletion test cuts the other way and matters as much: removing exposure to the lipids enhanced inflammation, and injecting them brought it back down to healthy levels. In liver cells in vitro, repeated exposure to the lipids improved mitochondrial functioning overall.

Where does fiber come in?

Diet strongly modulates how much glycine lipid the microbiome produces, and the team's dietary lever was fiber: a combination of pea fiber and citrus peel fiber raised microbiome glycine lipid levels after the Western diet had suppressed them. That makes the pathway, at least in mice, a diet-to-microbe-to-mitochondria chain rather than a drug story. Translationally, the researchers did the right first check: using human liver tissue from the UConn Health Research Biorepository, they confirmed the lipids are detectable in human liver — presence, not proof of effect. Blesso's group is starting a fiber intervention study in humans to see whether fiber supplementation changes glycine lipid levels in people, and describes funding and time as the biggest limitations on the many open questions.

What happened in muscle?

The companion Journal of Physiology study, led by kinesiology researcher Oh Sung Kwon, asked what the lipids do in skeletal muscle, where mitochondria decide how fat is burned. In male Ldlr-knockout mice fed a Western diet for eight weeks, L1256 accumulated in skeletal muscle and improved mitochondrial respiration supported by fatty acids — a direct measure of the mitochondria's capacity to use fat as fuel. It also increased proteins involved in mitochondrial energy production and antioxidant defense and helped preserve muscle fiber size. L654 influenced gene expression and inflammatory signaling but did not produce comparable improvements in respiration — a useful internal contrast showing the effect is lipid-specific, not a generic 'bacterial fat' story. The authors' own framing is the right size: the next question is whether similar responses occur in humans.

Where the evidence stands

• Established: Bacteroidota species in the gut and mouth produce glycine lipids that circulate systemically; mitochondrial biogenesis and fat-oxidation programs are central to liver and muscle metabolism; and MASLD affects roughly 30% of adults with limited treatment options.
• Preliminary: In Western-diet mouse models (Anto et al., Gastro Hep Advances 2026, DOI 10.1016/j.gastha.2026.101064; Kim et al., J Physiol 2026, DOI 10.1113/jp291898), L654/L1256 injections attenuated MASLD severity and enhanced mitochondrial-biogenesis and fat-oxidation genes; L1256 improved fatty-acid-supported muscle mitochondrial respiration and preserved fiber size; fiber feeding raised glycine lipid levels; and the lipids were detected in human liver tissue.
• Absent: Any human efficacy data, human dose information, and any demonstration that raising glycine lipids changes human liver or muscle outcomes — a human fiber-intervention study is being started.