Social anxiety disorder-associated gut microbiota increases social fear

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 121; no. 1; p. e2308706120
• Main Authors: Ritz, Nathaniel L, Brocka, Marta, Butler, Mary I, Cowan, Caitlin S M, Barrera-Bugueño, Camila, Turkington, Christopher J R, Draper, Lorraine A, Bastiaanssen, Thomaz F S, Turpin, Valentine, Morales, Lorena, Campos, David, Gheorghe, Cassandra E, Ratsika, Anna, Sharma, Virat, Golubeva, Anna V, Aburto, Maria R, Shkoporov, Andrey N, Moloney, Gerard M, Hill, Colin, Clarke, Gerard, Slattery, David A, Dinan, Timothy G, Cryan, John F
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 02.01.2024
• Subjects: Animals; Anxiety; Anxiety - psychology; Anxiety disorders; Biological Sciences; Fear; Gastrointestinal Microbiome - physiology; Hormones; Humans; Immune response; Intestinal microflora; Mice; Microbiomes; Microbiota; Microorganisms; Oxytocin; Phobia, Social; RNA, Ribosomal, 16S - genetics; rRNA 16S; Social anxiety; Stria terminalis; Therapeutic targets; microbiota-gut-brain axis; social phobia; microbiome; faecal transplant
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2308706120

Social anxiety disorder (SAD) is a crippling psychiatric disorder characterized by intense fear or anxiety in social situations and their avoidance. However, the underlying biology of SAD is unclear and better treatments are needed. Recently, the gut microbiota has emerged as a key regulator of both brain and behaviour, especially those related to social function. Moreover, increasing data supports a role for immune function and oxytocin signalling in social responses. To investigate whether the gut microbiota plays a causal role in modulating behaviours relevant to SAD, we transplanted the microbiota from SAD patients, which was identified by 16S rRNA sequencing to be of a differential composition compared to healthy controls, to mice. Although the mice that received the SAD microbiota had normal behaviours across a battery of tests designed to assess depression and general anxiety-like behaviours, they had a specific heightened sensitivity to social fear, a model of SAD. This distinct heightened social fear response was coupled with changes in central and peripheral immune function and oxytocin expression in the bed nucleus of the stria terminalis. This work demonstrates an interkingdom basis for social fear responses and posits the microbiome as a potential therapeutic target for SAD.