Effects of Lactiplantibacillus plantarum DSM 33464 in children with elevated blood lead levels: A randomized, double-blind, placebocontrolled study

Wenjing Ji¹Delphine Marie Anne Saulnier^2*Lan Zhang^3,4Jingxia Liu⁵Jisheng Gao⁶Xia Wang⁷Caterina Holz²Aimin Liang¹Hern-Tze Tina Tan⁸

• ¹Beijing Children's Hospital Capital Medical University, Beijing, China
• ²Novozymes Berlin, Berlin, Germany
• ³Chengdu Women and Children's Central Hospital, Chengdu, China
• ⁴University of Electronic Science and Technology of China, Chengdu, China
• ⁵Baoding Children's Hospital, Baoding, China
• ⁶Xuzhou Children's Hospital, Xuzhou, China
• ⁷Children's Hospital of Hebei Province, Hebei, China
• ⁸Novonesis, Cork, Ireland

Approximately one-third of the world's children have elevated blood lead levels (BLLs), that may lead to often-irreversible decreased intelligence, behavioral difficulties and learning problems. Identification and removal of the source of lead and good nutrition are the only advocated initial management, with chelation therapy for higher threshold BLLs. Probiotics have shown promising beneficial effects pre-clinically. Here, we investigated the safety and efficacy of the probiotic Lactiplantibacillus plantarum DSM 33464 in children with elevated blood lead levels. Methods: Children aged 3-12 years with elevated BLLs (>3.5 ug/dL) were enrolled in a randomized double-blind placebo-controlled multi-centered study and received either probiotic (1x10 9 colony forming units) or placebo (control group), along with a multivitamin/mineral supplement in both groups daily for 12 weeks. Results: Overall, 66 children were randomized, 54 received intervention (probiotic; n=30 and control; n= 24). The probiotic was well-tolerated. Probiotic, combined with multivitamin/mineral supplement, significantly reduced the BLLs in these children within 12 weeks of supplementation by 40%, similar to control group that received placebo plus multivitamin/mineral supplement. Larger reduction of urine lead levels at 8 weeks was observed in the probiotic group, along with reduction of abdominal pain and psychosomatic feelings at week 12. No depletion of essential minerals was observed in any of the groups. This study adds to previous findings suggesting that probiotic intervention may be a promising additional strategy to help reduce BLLs and its detrimental effects in children. Due to the preliminary nature of this study, larger studies investigating the effects of the strain alone, with longer intervention period are warranted to confirm the benefits observed. ClinicalTrials.gov registration: NCT04891666