{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T07:10:20Z","timestamp":1772521820989,"version":"3.50.1"},"reference-count":133,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:sec>\n                    <jats:title>Theoretical framework<\/jats:title>\n                    <jats:p>Cigarette smoking is the leading preventable cause of death worldwide, with nicotine dependence notably common among individuals with Substance Use Disorders (SUD). Smoking exacerbates both physical and mental health issues, further complicating the treatment of SUD. Current therapeutic approaches for SUD often prove inadequate, indicating a need for new strategies. Recent advancements in metabolomics and gut microbiome research have provided valuable insights into the biological mechanisms underlying addiction, warranting further investigation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study aims to investigate the therapeutic potential of smoking cessation for individuals with SUD, using a Cognitive-Behavioral Therapy (CBT) six-week group intervention within a therapeutic community. The research specifically explores the psychobehavioral, metabolic, and gut microbiome domains. It is hypothesized that smoking cessation will improve emotional regulation self-efficacy and reduce substance craving, mediated by changes in metabolic and microbiome profiles linked to brain systems of affect and reward.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A randomized controlled trial (N\u00a0=\u00a0100) will be conducted, examining outcomes such as clinical relapse rates as well as microbial and metabolic markers, investigating pathways of short-chain fatty acids, oxidative stress and inflammation, lipid, tryptophan, and one-carbon metabolism. Participants will undergo a CBT smoking cessation intervention, with pre- and post-assessments, compared to a control group receiving treatment as usual. Metabolomic and microbiome analyses will be conducted using blood and stool samples, alongside psychological assessments via questionnaires. Covariate analyses will be undertaken to control for metabolic and gut microbial effects of long-term psychiatric medications (antidepressants, mood stabilizers, antipsychotics, and opioid substitutions) present in the sample. Behavioral assessments will be conducted at a 3-month follow-up. The study is registered at clinicaltrials.gov under NCT06803706.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Level of originality<\/jats:title>\n                    <jats:p>This research will enhance our understanding of the complex interplay between smoking and mental health, offering potential for more effective treatment strategies for SUD. The current study\u2019s focus on connections between metabolic and gut microbiome pathways with affect and reward is expected to yield valuable insights into addiction mechanisms and improve diagnostic and therapeutic practices.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:related-object>\n                      <jats:ext-link>https:\/\/clinicaltrials.gov\/study\/NCT06803706?cond=metabolomic%20and%20microbial%20biomarkers%20in%20smoking%20cessation&amp;amp;rank=1<\/jats:ext-link>\n                      , identifier NCT06803706.\n                    <\/jats:related-object>\n                  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