Gut Microbiome and Its Bidirectional Pathway With Neurochemistry

Dilip Jeste, MD, presented research on the gut microbiome as a psychobiological determinant of health, with particular focus on its relationship to loneliness and social connection.

Jeste described the gut microbiome (made up of bacteria, viruses, and fungi) as having a bidirectional relationship with the brain, where specific neural circuits and neurotransmitters influence gut microbial composition and gut microbes affect neurochemistry and brain function. He situated this work within the broader public health crisis of loneliness, citing former US Surgeon General Vivek Murthy's finding that more people die from loneliness than from stroke or lung cancer, and the World Health Organization's estimate that approximately 1.3 billion people worldwide experience loneliness, roughly half of whom also carry a diagnosis of mental illness.¹

Jeste reported that his research group had consistently identified wisdom as the most effective antidote to loneliness across multiple studies. He defined wisdom as a multidimensional personality trait encompassing empathy, compassion, emotional regulation, balanced perspective, and openness to differing viewpoints. Both cross-sectional and longitudinal analyses demonstrated that individuals with higher baseline wisdom scores, particularly on the compassion subscale, were significantly less likely to have loneliness 5 to 7 years later. He noted that other investigators have reported significant improvement in loneliness with a wisdom-promoting intervention.²

Jeste connected wisdom and loneliness to gut microbiome composition, framing the gut-brain axis as a potential biological mechanism through which social and psychological states influence and are influenced by microbial health, with implications for both prevention and intervention in loneliness-related psychiatric morbidity.

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. WHO commission on social connection. World Health Organization. Accessed May 15, 2026. https://www.who.int/groups/commission-on-social-connection

2. Jiang D, Tang VFY, Kahlon M, et al. Effects of wisdom-enhancement narrative-therapy and empathy-focused interventions on loneliness over 4 weeks among older adults: a randomized controlled trial. Am J Geriatr Psych. 2025;33:18–30.