Gut microbes-spinal connection is required for itch sensation

Area of Science:

• Neuroscience
• Microbiology
• Immunology

Background:

• The gut microbiota's role in neurological disorders is established.
• The connection between gut microbes and chronic itch remains unclear.
• Chronic itch significantly impacts patients' physical and mental well-being.

Purpose of the Study:

• To investigate the involvement of gut microbiota in the development of chronic itch.
• To elucidate the mechanisms underlying the gut-brain axis in itch modulation.

Main Methods:

• Antibiotic-induced gut microbiota depletion in mice.
• Germ-free mouse models.
• Oral gavage with *Bacteroides fragilis*.
• Analysis of FTO expression, RNA m6A modification, and MRGPRF protein levels.
• Investigation of ETS1 transcription factor activity.

Main Results:

• Gut microbiota depletion enhanced itch tolerance in mice.
• *Bacteroides fragilis* administration corrected antibiotic-induced itch dysfunction.
• This correction was mediated by the metabolite acetyl-l-carnitine (ALC).
• Microbiota depletion decreased FTO expression, increasing RNA m6A sites in *MrgprF* mRNA, reducing MRGPRF protein.
• FTO downregulation was linked to ETS1 inactivation.

Conclusions:

• A gut microbe-spinal cord connection modulates itch sensation via RNA N6-methyladenosine (m6A) epigenetic mechanisms.
• *Bacteroides fragilis* and its metabolite ALC play a critical role in linking gut microbiota alterations to itch dysfunction.
• Targeting the gut microbiota and its metabolites offers a potential therapeutic strategy for chronic itch.