Intestinal metabolites predict treatment resistance of patients with depression and anxiety

Juntaro Matsuzaki, Shunya Kurokawa, Chiaki Iwamoto, Katsuma Miyaho, Akihiro Takamiya, Chiharu Ishii, Akiyoshi Hirayama, Kenji Sanada, Shinji Fukuda, Masaru Mimura, Taishiro Kishimoto, Yoshimasa Saito

Research output: Contribution to journalArticlepeer-review


Background: The impact of the gut microbiota on neuropsychiatric disorders has gained much attention in recent years; however, comprehensive data on the relationship between the gut microbiome and its metabolites and resistance to treatment for depression and anxiety is lacking. Here, we investigated intestinal metabolites in patients with depression and anxiety disorders, and their possible roles in treatment resistance. Results: We analyzed fecal metabolites and microbiomes in 34 participants with depression and anxiety disorders. Fecal samples were obtained three times for each participant during the treatment. Propensity score matching led us to analyze data from nine treatment responders and nine non-responders, and the results were validated in the residual sample sets. Using elastic net regression analysis, we identified several metabolites, including N-ε-acetyllysine; baseline levels of the former were low in responders (AUC = 0.86; 95% confidence interval, 0.69–1). In addition, fecal levels of N-ε-acetyllysine were negatively associated with the abundance of Odoribacter. N-ε-acetyllysine levels increased as symptoms improved with treatment. Conclusion: Fecal N-ε-acetyllysine levels before treatment may be a predictive biomarker of treatment-refractory depression and anxiety. Odoribacter may play a role in the homeostasis of intestinal L-lysine levels. More attention should be paid to the importance of L-lysine metabolism in those with depression and anxiety.

Original languageEnglish
Article number8
JournalGut Pathogens
Issue number1
Publication statusPublished - 2024 Dec


  • Anxiety
  • Depression
  • Elastic net analysis
  • N-ε-acetyllysine
  • Odoribacter

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Gastroenterology
  • Virology
  • Infectious Diseases


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