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(Blattodea: Ectobiidae) is a major urban pest with widespread insecticide resistance. This study evaluated the synergistic effect of combining Metarhizium anisopliae with beta-cypermethrin (\u03b2-CYP) and investigated its mechanisms. Compatibility assays showed that \u03b2-CYP (1\u201310 \u03bcg\/mL) was highly compatible with M. anisopliae (1 \u00d7 107\u20131 \u00d7 109 cfu\/mL), with enhanced compatibility at lower concentrations. Bioassays confirmed significant synergy, increasing mortality and shortening median lethal time. Mechanistically, the combination accelerated histopathological damage to the midgut, hindgut, Malpighian tubules, and fat body, while promoting fungal proliferation in hemolymph and gut tissues. 16S rRNA sequencing revealed gut microbiota dysbiosis: Firmicutes replaced Bacteroidetes as the dominant phylum, opportunistic pathogens (Weissella, Alistipes) increased, and beneficial bacteria (Enterococcus, Fusobacterium) decreased. Weissella recolonization experiments confirmed its mortality-enhancing role. Additionally, the combination suppressed carboxylesterase activity and modulated immune gene expression (CYP4G19, BgPo), compromising host defense. Collectively, these findings demonstrate that \u03b2-CYP and M. anisopliae exert synergistic effects through multi-target mechanisms, offering a promising integrated pest management strategy that reduces chemical usage while enhancing biocontrol efficacy.<\/jats:p>","DOI":"10.3390\/insects17090896","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T10:59:23Z","timestamp":1787741963000},"page":"896","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synergistic Control of Blattella germanica by Beta-Cypermethrin and Metarhizium anisopliae: Disruption of Gut Microbiota, Histopathology, and Detoxification Systems"],"prefix":"10.3390","volume":"17","author":[{"given":"Xiaoyan","family":"Wu","sequence":"first","affiliation":[{"name":"Medical School, Shandong Xiehe University, Jinan 250109, China"},{"name":"Shandong Province Key Laboratory of Emerging Contaminants Risk Prevention and Control, College of Life Science, Shandong Normal University, Jinan 250358, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Wang","sequence":"additional","affiliation":[{"name":"Shandong Province Key Laboratory of Emerging Contaminants Risk Prevention and Control, College of Life Science, Shandong Normal University, Jinan 250358, China"},{"name":"Dongying Key Laboratory of Salt Tolerance Mechanism and Application of Halophytes, Dongying Institute, Shandong Normal University, Dongying 257000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3878-4344","authenticated-orcid":false,"given":"Tong","family":"Cai","sequence":"additional","affiliation":[{"name":"Shandong Center for Disease Control and Prevention, Jinan 250013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caixia","family":"Liu","sequence":"additional","affiliation":[{"name":"Shandong Province Key Laboratory of Emerging Contaminants Risk Prevention and Control, College of Life Science, Shandong Normal University, Jinan 250358, China"},{"name":"Dongying Key Laboratory of Salt Tolerance Mechanism and Application of Halophytes, Dongying Institute, Shandong Normal University, Dongying 257000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Huang","sequence":"additional","affiliation":[{"name":"Shandong Province Key Laboratory of Emerging Contaminants Risk Prevention and Control, College of Life Science, Shandong Normal University, Jinan 250358, China"},{"name":"Dongying Key Laboratory of Salt Tolerance Mechanism and Application of Halophytes, Dongying Institute, Shandong Normal University, Dongying 257000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianzheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Shandong Province Key Laboratory of Emerging Contaminants Risk Prevention and Control, College of Life Science, Shandong Normal University, Jinan 250358, China"},{"name":"Dongying Key Laboratory of Salt Tolerance Mechanism and Application of Halophytes, Dongying Institute, Shandong Normal University, Dongying 257000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejun","family":"Wang","sequence":"additional","affiliation":[{"name":"Shandong Center for Disease Control and Prevention, Jinan 250013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3281-6325","authenticated-orcid":false,"given":"Fan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shandong Province Key Laboratory of Emerging Contaminants Risk Prevention and Control, College of Life Science, Shandong Normal University, Jinan 250358, China"},{"name":"Dongying Key Laboratory of Salt Tolerance Mechanism and Application of Halophytes, Dongying Institute, Shandong Normal University, Dongying 257000, China"},{"name":"Key Laboratory of Animal Resistance Biology of Shandong Province, College of Life Science, Shandong Normal University, 88 East Wenhua Road, Jinan 250014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1007\/s12639-021-01381-2","article-title":"First report of Lophomonas spp. in German cockroaches (Blattella germanica) trapped in hospitals, northern Iran","volume":"45","author":"Shemshadian","year":"2021","journal-title":"J. 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