PMID- 29843725 OWN - NLM STAT- MEDLINE DCOM- 20181217 LR - 20240318 IS - 1476-069X (Electronic) IS - 1476-069X (Linking) VI - 17 IP - 1 DP - 2018 May 29 TI - The Ramazzini Institute 13-week pilot study on glyphosate and Roundup administered at human-equivalent dose to Sprague Dawley rats: effects on the microbiome. PG - 50 LID - 10.1186/s12940-018-0394-x [doi] LID - 50 AB - BACKGROUND: Glyphosate-based herbicides (GBHs) are broad-spectrum herbicides that act on the shikimate pathway in bacteria, fungi, and plants. The possible effects of GBHs on human health are the subject of an intense public debate for both its potential carcinogenic and non-carcinogenic effects, including its effects on microbiome. The present pilot study examines whether exposure to GBHs at doses of glyphosate considered to be "safe" (the US Acceptable Daily Intake - ADI - of 1.75 mg/kg bw/day), starting from in utero, may modify the composition of gut microbiome in Sprague Dawley (SD) rats. METHODS: Glyphosate alone and Roundup, a commercial brand of GBHs, were administered in drinking water at doses comparable to the US glyphosate ADI (1.75 mg/kg bw/day) to F0 dams starting from the gestational day (GD) 6 up to postnatal day (PND) 125. Animal feces were collected at multiple time points from both F0 dams and F1 pups. The gut microbiota of 433 fecal samples were profiled at V3-V4 region of 16S ribosomal RNA gene and further taxonomically assigned and assessed for diversity analysis. We tested the effect of exposure on overall microbiome diversity using PERMANOVA and on individual taxa by LEfSe analysis. RESULTS: Microbiome profiling revealed that low-dose exposure to Roundup and glyphosate resulted in significant and distinctive changes in overall bacterial composition in F1 pups only. Specifically, at PND31, corresponding to pre-pubertal age in humans, relative abundance for Bacteriodetes (Prevotella) was increased while the Firmicutes (Lactobacillus) was reduced in both Roundup and glyphosate exposed F1 pups compared to controls. CONCLUSIONS: This study provides initial evidence that exposures to commonly used GBHs, at doses considered safe, are capable of modifying the gut microbiota in early development, particularly before the onset of puberty. These findings warrant future studies on potential health effects of GBHs in early development such as childhood. FAU - Mao, Qixing AU - Mao Q AD - Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1428 Madison, New York, NY, 10029, USA. AD - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China. FAU - Manservisi, Fabiana AU - Manservisi F AD - Cesare Maltoni Cancer Research Center (CMCRC), Ramazzini Institute (RI), Via Saliceto, 3, 40010 Bentivoglio, Bologna, Italy. AD - Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy. FAU - Panzacchi, Simona AU - Panzacchi S AD - Cesare Maltoni Cancer Research Center (CMCRC), Ramazzini Institute (RI), Via Saliceto, 3, 40010 Bentivoglio, Bologna, Italy. FAU - Mandrioli, Daniele AU - Mandrioli D AD - Cesare Maltoni Cancer Research Center (CMCRC), Ramazzini Institute (RI), Via Saliceto, 3, 40010 Bentivoglio, Bologna, Italy. AD - Department of Agricultural Sciences, University of Bologna, Bologna, Italy. FAU - Menghetti, Ilaria AU - Menghetti I AD - Cesare Maltoni Cancer Research Center (CMCRC), Ramazzini Institute (RI), Via Saliceto, 3, 40010 Bentivoglio, Bologna, Italy. FAU - Vornoli, Andrea AU - Vornoli A AD - Cesare Maltoni Cancer Research Center (CMCRC), Ramazzini Institute (RI), Via Saliceto, 3, 40010 Bentivoglio, Bologna, Italy. FAU - Bua, Luciano AU - Bua L AD - Cesare Maltoni Cancer Research Center (CMCRC), Ramazzini Institute (RI), Via Saliceto, 3, 40010 Bentivoglio, Bologna, Italy. FAU - Falcioni, Laura AU - Falcioni L AD - Cesare Maltoni Cancer Research Center (CMCRC), Ramazzini Institute (RI), Via Saliceto, 3, 40010 Bentivoglio, Bologna, Italy. FAU - Lesseur, Corina AU - Lesseur C AD - Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, 1428 Madison, New York, NY, 10029, USA. FAU - Chen, Jia AU - Chen J AD - Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, 1428 Madison, New York, NY, 10029, USA. FAU - Belpoggi, Fiorella AU - Belpoggi F AD - Cesare Maltoni Cancer Research Center (CMCRC), Ramazzini Institute (RI), Via Saliceto, 3, 40010 Bentivoglio, Bologna, Italy. belpoggif@ramazzini.it. FAU - Hu, Jianzhong AU - Hu J AD - Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1428 Madison, New York, NY, 10029, USA. LA - eng GR - P30 ES023515/ES/NIEHS NIH HHS/United States GR - NIH/NIEHS P30ES023515/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20180529 PL - England TA - Environ Health JT - Environmental health : a global access science source JID - 101147645 RN - 0 (Herbicides) RN - TE7660XO1C (Glycine) SB - IM MH - Animals MH - Bacteria/classification/drug effects MH - Dose-Response Relationship, Drug MH - Female MH - Gastrointestinal Microbiome/*drug effects MH - Glycine/adverse effects/*analogs & derivatives MH - Herbicides/*adverse effects MH - Male MH - Pilot Projects MH - Rats MH - Rats, Sprague-Dawley MH - Glyphosate PMC - PMC5972442 OTO - NOTNLM OT - Early developmental stage OT - Glyphosate OT - Gut microbiome OT - Roundup COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2018/05/31 06:00 MHDA- 2018/12/18 06:00 PMCR- 2018/05/29 CRDT- 2018/05/31 06:00 PHST- 2018/02/02 00:00 [received] PHST- 2018/05/10 00:00 [accepted] PHST- 2018/05/31 06:00 [entrez] PHST- 2018/05/31 06:00 [pubmed] PHST- 2018/12/18 06:00 [medline] PHST- 2018/05/29 00:00 [pmc-release] AID - 10.1186/s12940-018-0394-x [pii] AID - 394 [pii] AID - 10.1186/s12940-018-0394-x [doi] PST - epublish SO - Environ Health. 2018 May 29;17(1):50. doi: 10.1186/s12940-018-0394-x.