Mitigating lead-induced osteoporosis: The role of butyrate in gut-bone axis restoration

• Published in: Ecotoxicology and environmental safety Vol. 283; p. 116943
• Main Authors: Ge, Yuqiu, Jia, Zhongtang, Zhao, Shiting, Zhang, WenChao, Shi, Xian, Xie, Ruijin, Gong, Yan, Sheng, Jixiang, van 't Hof, Rob J., Yang, Jiatao, Han, Chunqing, Hu, Xiping, Wang, Yafeng, Wu, Yu, Li, Chunping, Wang, Miaomiao
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 15-09-2024; Elsevier
• Subjects: Adolescent; Adult; Animals; Bone and Bones - drug effects; Butyrate; Butyrates - pharmacology; Butyric Acid - pharmacology; Female; Gastrointestinal Microbiome - drug effects; Gut-bone axis; Humans; Lead - toxicity; Lead exposure; Male; Mice; Mice, Inbred C57BL; Middle Aged; NHANES; Osteoporosis; Osteoporosis - chemically induced; Treg cell; Young Adult; PCoA; LefSe; OR; CTx; P1NP; OTUs; Treg cell; Treg; Tb.N; Gut-bone axis; Butyrate; GC-MS; Tb.Sp; Osteoporosis; BV/TV; Ct.Th; Ct.Ar/Tt.Ar; BMD; SCFAs; NHANES; Lead exposure; ELISA
• ISSN: 0147-6513; 1090-2414; 1090-2414
• DOI: 10.1016/j.ecoenv.2024.116943

Lead (Pb) is an environmentally widespread bone toxic pollutant, contributes to the development of osteoporosis. Butyric acid, mainly produced by the fermentation of indigestible dietary fiber by gut microbiota, plays a pivotal role in the maintenance of bone homeostasis. However, the effects of butyric acids on the Pb induced osteoporosis have not yet been elucidated. In this study, our results showed that Pb exposure was negatively related to the abundance of butyric acid, in the Pb-exposed population and Pb-exposed mice. Pb exposure caused gut microbiota disorders, resulting in the decline of butyric acid-producing bacteria, such as Butyrivibrio_crossotus, Clostridium_sp._JN9, and the butyrate-producing enzymes through the acetyl-CoA pathway. Moreover, results from the NHANES data suggested that dietary intake of butyrate was associated with a reduced risk of osteoporosis in lead-burdened populations, particularly among men or participants aged 18–60 years. In addition, butyrate supplementation in mice with chronic Pb exposure improved the bone microarchitectures, repaired intestinal damage, upregulated the proportion of Treg cells. Taken together, these results demonstrated that chronic Pb exposure disturbs the gut-bone axis, which can be restored by butyric acid supplement. Our results suggest that butyrate supplementation is a possible therapeutic strategy for lead-induced bone toxicity.
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•Chronic lead exposure decreases butyric acid content and its producing bacteria.•Butyrate diet reduces the risk of osteoporosis in lead-burdened populations.•Butyrate supplement restores gut-bone axis disturbed by chronic lead exposure.