Table 1.

Effects of endocrine disruptors on the gut microbiota in in vitro assays.

References	Compound	Dose Exposure	Justification of Exposure Dose	Species Strain Mode	Methods	Outcomes	Conclusions
Van de Wiele et al. (2010) [35]	Metal (Arsenic)	10 μg methylarsenical/g biomass/hr and 28 μg as-contaminated soils/g biomass/hr	Concentrations detected in arsenic contaminated soils in urban areas of the EEUU	Strains isolated from human feces	HPLC; plasma mass spectrometry	High degree of methylation of Methylarsenical and As-contaminated soils in colon digestion.	Human microbiota has ability to actively metabolize As into methylated arsenicals and thioarsenicals.
Wang et al. (2018) [28]	BPA	25 μg/L, 250 μg/L, and 2500 μg/L	High human relevant exposure dose; EPA reference dose; 1% lowest observed adverse effect level	Humans	In vitro SHIME, 16S rRNA gene sequencing, and PCR	BPA exposure decreased the diversity of gut microbioma (ascending colon and the transverse colon). Exposure to BPA of 25 μg/L decreased diversity of gut microbioma, but high-level exposures (250 and 2500 μg/L) increased diversity (descending colon).	Exposure to BPA significantly altered the microbiota and increased the proportion of shared microbes.
Hoffman et al. (2019) [36]	PCB126	20 or 200 μM	Concentrations physiologically relevant, especially in heavily exposed populations	C56BL6/J mice	16S rRNA gene sequencing, PCR, and HPLC	Significant reduction in bacterial growth after exposure to high concentrations of PCB 126 compared to control. Not significant reduction in bacterial growth at PCB concentrations below 20 µM.	Exposure to PCB126 can contribute to alterations in host metabolism through mechanisms dependent on the intestinal microbiota, specifically through bacterial fermentation or membrane disruption.
Lei et al. (2019) [37]	Di (2-ethylhexyl) phthalate	10 or 100 µM	The concentration mimics human exposure during adolescence by continually exposing mice to phthalate from ages 6 to 8 weeks	C57BL/6J mice	16S rRNA gene sequencing and a triple-quadrupole time-of-flight instrument coupled to a binary pump HPLC system	Exposure of in vitro cecal microbiota to di (2-ethylhexyl)-phthalate increased the abundance of Alistipes, Paenibacillus, and Lachnoclostridium. Non-directed metabolomics showed that di (2-ethylhexyl)-phthalate greatly altered the metabolite profile in the culture.	Di (2-ethylhexyl)-phthalate can directly affect the production of bacterial metabolites related to neurodevelopmental disorders.
Joly et al. (2013) [38]	Chlorpyrifos	1 mg/kg/day	NOAEL	Wistar rats	SHIME	Exposure to chlorpyrifos increased Bacteroides spp. and Enterococcus spp. and reduced Bifidobacterium spp. and Lactobacillus spp.	Chronic, low-dose exposure to chlorpyrifos causes gut dysbiosis.
Shehata et al. (2013) [39]	Glyphosate	5.0, 2.40, 1.20, 0.60, 0.30, 0.15, and 0.075 mg/mL	To determine the minimal inhibitory concentration	Chickens	MALDI–TOF MS analysis, multiplex PCR	In vitro exposure to glyphosate showed resistance to glyphosate in highly pathogenic bacteria, but most beneficial bacteria showed susceptibility to glyphosate.	Glyphosate exposure showed differences in sensitivity between pathogenic and beneficial microbiota. Ingestion of glyphosate-contaminated food reduced the beneficial microbiota.
Ackermann et al. (2015) [40]	Glyphosate	0, 1, 10, and 100 μg/mL	Concentrations lower than NOAEL	Cows	DAISYII-incubators, FISH with 16S rRNA/23S rRNA-targeted	Exposure to 1 and 10 μg/mL glyphosate reduced abundances of all species except for Isotricha spp. and Diplodinium spp. Exposure to 100 μg/mL glyphosate reduced abundance of Diplodinium spp.	Glyphosate inhibits growth of beneficial bacteria, but increases the population of pathogenic bacteria
Riede et al. (2016) [41]	Glyphosate	0.42 or 2.92 mg/L	The low dose reflects the estimated maximum dietary glyphosate intake of dairy cattle, according to model assumptions. The high dose is higher than residues found in the beef cattle diet.	Cows	RUSITEC experiments, LC-MS/MS method, 16S rRNA gene sequencing, and PCR	Effects of glyphosate at concentrations of 0.42 or 2.92 mg/L. After the incubation period only observed subtle changes in the composition of ruminal bacteria.	No major changes were observed due to Glyphosate exposure to ruminal metabolism or the composition of bacterial communities.

HPLC: high performance liquid chromatography; PCR: polymerase chain reaction; SHIME: simulator of the human intestinal microbial ecosystem; FISH: fluorescence in situ hybridation; MALDI-TOF MS: matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; RUSITEC: rumen simulation technique; NOAEL: no observed adverse effects level.