Bariatric surgery induces sustained weight loss and metabolic benefits via notable effects on the gut–brain axis that lead to alterations in the neuroendocrine regulation of appetite and glycaemia. However, in a subset of patients, bariatric surgery is associated with adverse effects on mental health, including increased risk of suicide or self-harm as well as the emergence of depression and substance use disorders. The contributing factors behind these adverse effects are not well understood. Accumulating evidence indicates that there are important links between gut-derived hormones, microbial and bile acid profiles, and disorders of mood and substance use, which warrant further exploration in the context of changes in gut–brain signalling after bariatric surgery. Understanding the basis of these adverse effects is essential in order to optimize the health and well-being of people undergoing treatment for obesity.
After bariatric surgery, a subset of patients experience adverse mental health outcomes such as depression, anxiety, and increased use of alcohol and drugs.
Preclinical and clinical studies link appetite-related gut peptides, including ghrelin, glucagon-like peptide 1, peptide YY and cholecystokinin, with depression and anxiety.
Central ghrelin signalling seems to be involved in driving increases in the rewarding properties of alcohol following bariatric surgery.
Gut bacteria might influence mood and behaviour, and exposure to drugs of abuse, such as alcohol and opioids, induces gut microbial dysbiosis.
Emerging literature indicates that bile acids can have central effects on mood and behavioural responses induced by cocaine.
Taken together, these findings implicate potential mechanisms by which bariatric surgery could influence mood and behaviour; further research is essential to understand and prevent adverse mental health outcomes after bariatric surgery.
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This manuscript received no external funding. R.M.B. acknowledges the support of an ARC DECRA Fellowship (DE190101244). P.S. acknowledges the support of a National Health and Medical Research Council Investigator Grant (1178482). We acknowledge the numerous researchers whose work we were unable to cite due to space limitations.
C.W.l.R. reports grants from Science Foundation Ireland and grants from Health Research Board during the conduct of the study; other from Novo Nordisk and GI Dynamics, personal fees from Eli Lilly, grants and personal fees from Johnson and Johnson, personal fees from Sanofi Aventis, Astra Zeneca, Janssen, Bristol-Myers Squibb and Boehringer-Ingelheim outside the submitted work. P.S. reports personal fees from Novo Nordisk outside the submitted work. The other authors declare no competing interests.
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Brown, R.M., Guerrero-Hreins, E., Brown, W.A. et al. Potential gut–brain mechanisms behind adverse mental health outcomes of bariatric surgery. Nat Rev Endocrinol 17, 549–559 (2021). https://doi.org/10.1038/s41574-021-00520-2
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