{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:28:01Z","timestamp":1785432481693,"version":"3.56.0"},"reference-count":62,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017170","name":"Thailand Science Research and Innovation","doi-asserted-by":"crossref","award":["TUFT-FF49\/2569"],"award-info":[{"award-number":["TUFT-FF49\/2569"]}],"id":[{"id":"10.13039\/501100017170","id-type":"DOI","asserted-by":"crossref"}]},{"award":["TUFT-FF49\/2569"],"award-info":[{"award-number":["TUFT-FF49\/2569"]}],"id":[{"id":"https:\/\/ror.org\/000025p04","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005790","name":"Thammasat University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005790","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/002yp7f20","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004704","name":"National Research Council of Thailand","doi-asserted-by":"publisher","award":["N42A671041"],"award-info":[{"award-number":["N42A671041"]}],"id":[{"id":"10.13039\/501100004704","id-type":"DOI","asserted-by":"publisher"}]},{"award":["N42A671041"],"award-info":[{"award-number":["N42A671041"]}],"id":[{"id":"https:\/\/ror.org\/018wfhg78","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Background: Insomnia and stress-related sleep disorders are increasingly recognized as systemic conditions linked to the microbiota\u2013gut\u2013brain axis (MGBA). With growing clinical interest in natural products that modulate the gut environment, this systematic review evaluates the efficacy and mechanisms of non-pharmacological interventions, specifically probiotics, prebiotics, dietary indices, and botanicals, in alleviating insomnia, restoring circadian rhythms, and modulating neurochemical markers. Methods: In strict accordance with PRISMA 2020 guidelines, we searched PubMed, ScienceDirect, Scopus, and The Cochrane Library for English language studies published from inception to March 31, 2026. Eligibility was restricted to studies with rigorously controlled designs, specifically randomized controlled trials (RCTs) and controlled in vivo animal studies. Interventions had to target the gut microbiota, with primary outcomes measuring sleep quality (subjective or objective) or sleep-related neurochemical markers. We excluded uncontrolled, single-arm, or observational designs; in vitro studies; non-original research; and studies involving subjects with severe medical or psychiatric comorbidities (e.g., cancer, ADHD, severe psychiatric disorders) to prevent confounding variables, though mild-to-moderate anxiety and depression were permitted. Risk of bias was assessed using the Cochrane RoB 2.0 and SYRCLE tools. Due to significant methodological heterogeneity, a narrative synthesis stratified by intervention and population was conducted. This review was not registered in PROSPERO. Results: A total of 56 studies (33 humans, 23 animals) met the inclusion criteria. Taxonomic nomenclature was updated to reflect 2020 reclassifications (e.g., Lactiplantibacillus plantarum). In human trials, interventions significantly improved subjective sleep metrics (PSQI, ISI). Recent additions demonstrated the efficacy of the Dietary Index for Gut Microbiota (DI-GM) and the improvement in N3 sleep latency by yeast mannan. Furthermore, whole-food patterns (e.g., the MIND diet) and Traditional Chinese Medicine (TCM) decoctions successfully enriched beneficial taxa, such as Bacteroides coprophilus, and increased short-chain fatty acid (SCFA) production. Animal models demonstrated that \u201cpsychobiotic\u201d strains (Bifidobacterium breve, Lacticaseibacillus paracasei), prebiotics (GOS\/PDX), and TCM formulas effectively restored GABA\/5-HT profiles, lowered morning cortisol, and facilitated REM rebound in PCPA-induced models, while also consolidating non-rapid eye movement (NREM) sleep and downregulating clock genes (Per1\/Per2). Conclusions: Psychobiotics, prebiotics, and botanicals represent a highly viable non-pharmacological strategy for treating insomnia. However, current evidence is constrained by a heavy reliance on subjective human questionnaires, short follow-up durations limiting insight into long-term stability, and a substantial translational gap between mechanistic rodent models and human clinical outcomes.<\/jats:p>","DOI":"10.3390\/biom16070933","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T03:06:34Z","timestamp":1782875194000},"page":"933","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gut Microbiota Modulation as a Therapeutic Strategy for Insomnia: A Systematic Review of Nutritional and Botanical Interventions"],"prefix":"10.3390","volume":"16","author":[{"given":"Narada","family":"Vicharnnikornkij","sequence":"first","affiliation":[{"name":"Graduate Program in Translational Biomedical Sciences and Innovation, Chulabhorn International College of Medicine, Thammasat University, Rangsit Campus, Pathumthani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3720-3878","authenticated-orcid":false,"given":"Wanna","family":"Chaijaroenkul","sequence":"additional","affiliation":[{"name":"Graduate Program in Translational Biomedical Sciences and Innovation, Chulabhorn International College of Medicine, Thammasat University, Rangsit Campus, Pathumthani 12120, Thailand"},{"name":"Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Thammasat University, Rangsit Campus, Pathumthani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kesara Na","family":"Bangchang","sequence":"additional","affiliation":[{"name":"Graduate Program in Translational Biomedical Sciences and Innovation, Chulabhorn International College of Medicine, Thammasat University, Rangsit Campus, Pathumthani 12120, Thailand"},{"name":"Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Thammasat University, Rangsit Campus, Pathumthani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"ref_1","unstructured":"Benedict, C., Kern, W., and Born, J. 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