Biology and Loneliness: Gut Microbiome Correlates

Dilip Jeste, MD, shared findings on the relationship between wisdom, loneliness, and gut microbiome diversity, with implications for population-level psychiatric intervention.

Jeste reported that his research group had consistently identified wisdom—defined as a multidimensional trait encompassing empathy, compassion, emotional regulation, and balanced perspective—as the most robust antidote to loneliness across both cross-sectional and longitudinal studies.¹ Individuals with higher wisdom scores, particularly on the compassion subscale, were significantly less likely to be lonely at baseline and were protected against developing loneliness 5 to 7 years later.²

The novel contribution of this work was the demonstration of an inverse relationship between the gut microbiome profiles associated with loneliness and those associated with wisdom and compassion. Jeste explained that loneliness was associated with reduced microbiome diversity (both alpha diversity, referring to variation in microbial species within an individual, and beta diversity, referring to variation in microbial species between individuals) whereas higher wisdom and compassion scores were associated with greater diversity across both measures. He framed this as demonstrating a bidirectional gut-brain axis model: "when we connect with people and have more social connections, the microbiome becomes more diverse, but also the other way around—if the microbiome is diverse, we are more likely to have more and higher quality social connection."

Jeste concluded that given the global scale of the loneliness epidemic, interventions aimed at cultivating wisdom and compassion at the population level represent a clinically and biologically grounded strategy for reducing loneliness-associated psychiatric and physical morbidity, with the gut-brain axis serving as a likely mechanistic pathway.

Dr Jeste is director of the Global Research Network on Social Determinants of Mental Health and Exposomics, president elect of the World Federation for Psychotherapy, and editor-in-chief of the International Psychogeriatrics journal, and a former professor of psychiatry and distinguished researcher at the University of California in San Diego, and former president of the American Psychiatric Association.

References

1. Jeste DV, Alexopoulos GS, Blazer DG, et al. Wisdom, resilience, and well-being in later life. Ann Rev Clin Psych. 2025;21(1):33-59.

2. Nguyen TT, Zhang X, Wu T-C, et al. Association of loneliness and wisdom with gut microbial diversity and composition: an exploratory study. Front Psychiatry. 2021;12:648475.