Microbiota-Derived Metabolite Butyrate as a Senomorphic
-
Butyrate levels in the colon are lower in older adults. And senescent T cells are higher in older adults. Can the number of senescent T cells be corrected to a more youthful levels?
ABSTRACT
Advancing age is accompanied by an accumulation of senescent T cells that secrete pro-inflammatory senescence-associated secretory phenotype (SASP) molecules. Gut-microbiota-derived signals are increasingly recognised as immunomodulators. In the current study, we demonstrated that ageing and the accumulation of senescent T cells are accompanied by a reduction in microbial-derived short-chain fatty acids (SCFAs). Culturing aged T cells in the presence of butyrate suppresses the induction of a senescence phenotype and inhibits the secretion of pro-inflammatory SASP factors, such as IL6 and IL8. Administration offaecal supernatants from young mice rich in butyrate prevented in vivo accumulation of senescent spleen cells in aged mice. The molecular pathways governing butyrate's senomorphic potential include a reduced expression of DNA damage markers, lower mitochondrial ROS accumulation, and downregulation of mTOR activation, which negatively regulates the transcription factorNFκB. Our findings establish butyrate as a potent senomorphic agent and provide the evidence base for future microbiome restitution intervention trials using butyrate supplements for combating T cell senescence, ultimately reducing inflammation and combating age-related pathologies to extend lifelong health.
-
I made an AI search to understand:
Context
Administration of faecal supernatants from young mice rich in butyrate prevented in vivo accumulation of senescent spleen cells in aged mice.
Faecal supernatants: Fecal pellets are processed (homogenized, centrifuged) to create a fecal suspension or supernatant.
Answer:
Fecal supernatants, derived from young mice and given to old mice (FMT), act as a potent anti-aging intervention, reversing gut, brain, and metabolic decline by transferring youthful microbiota and metabolites, improving cognition, reducing inflammation, enhancing gut barrier function, and boosting metabolism in old recipients, essentially making their microbiomes "younger" and improving overall health.
Key Findings & Effects
• Rejuvenates Gut Microbiome: Transfers beneficial microbes from young donors, restoring youthful diversity and function in aged guts.
• Improves Cognition & Brain Health: Enhances learning, memory, synaptic plasticity (like LTP), and reduces neuroinflammation, reversing age-related brain defects.
• Boosts Metabolism: Improves glucose metabolism and overall metabolic capacity in older recipients.
• Strengthens Gut Barrier: Reduces intestinal permeability, a key factor in aging and inflammation.
• Reduces Inflammation: Decreases pro-inflammatory markers and increases anti-inflammatory factors systemically.
• Enhances Physical Fitness: Can rejuvenate muscle and skin, and improve overall fitness in aged animals.
• Modulates Metabolites: Alters the fecal metabolome, increasing beneficial short-chain fatty acids (SCFAs) like butyrate and valerate.
How It Works (Mechanisms)- Microbial Transfer: Young feces contain a microbial community more diverse and functional than aged feces.
- Gut-Brain Axis: Changes in gut microbiota influence brain function through neural, hormonal, and immune pathways.
- Metabolic Signaling: Young microbiota produce metabolites (like SCFAs) that signal to the host, improving health.
- Immune System Modulation: Shifts the immune balance towards less inflammation.
Application in Studies
• Preparation: Fecal pellets are often processed (homogenized, centrifuged) to create a fecal suspension or supernatant.
• Administration: Given to old mice (often after antibiotic pre-treatment to clear existing microbes) via oral gavage.
In essence, young fecal transplants reprogram the aging gut, leading to systemic anti-aging effects and improved health in older mice, highlighting the microbiome's crucial role in aging.
doi: 10.1186/s40168-022-01243-w
So, in essence: Try to be gentle with what will end up in the stool. Some very young children with severe weakness and a microbiome imbalance have already received a fecal enema from their mother, with success.
-
@LucH -Thanks for your cautionary words.
