Table 2.

Effects of endocrine disruptors on the animal microbiota.

References	Compound	Dose Exposure	Justification of Exposure Dose	Species Strain Mode	Methods	Outcomes	Conclusions
Ba et al. (2017) [42]	Metals (Cadmium)	100 nM	Tolerable weekly intake.	C57BL/6J mice	16S rDNA sequencing. Fecal microbiota transplant.	Early exposure to low dose of cadmium results in adiposities in adult male mice as well as in reduced diversity and altered composition of gut microbiota.	Early exposure to cadmium resulted in increased fat deposits in male but not in female mice. Low cadmium concentrations increased the expression of genes related to lipid metabolism.
Wu et al. (2016) [43]	Metals (Lead)	32 ppm	Relevant concentration of Pb acetate in drinking water.	Non-agouti (a/a) AVy mice offspring	16S rRNA gene sequencing.	Perinatal Pb exposure was significantly associated with increased bodyweight in adult males (p < 0.05) but not in females (p = 0.24). Perinatal Pb exposure altered gut microbiota composition in adult offspring, even after stopping exposure at 3 weeks (sex-independent). Pseudomonas, Enterobacter, and Desulfovibrio increased in adult mice perinatally exposed to Pb (p < 0.05).	Perinatal Pb exposure was associated with bodyweight (sex-dependent response) and with microbiota composition changes (sex-independent).
Xia et al. (2018) [44]	Metals (Lead)	10 and 30 μg/L	Exposure dose is below the maximum allowable concentration of lead in water for zebrafish = 0.07 mg/L.	Zebrafish	16S rRNA gene sequencing and GC/MS metabolomics analysis.	Exposure to 30 μg/L Pb resulted in decrased α-Proteobacteria and increased Firmicutes. GC/MS metabolomics analysis showed that 41 metabolites were altered in the exposed group. Changes were related to glycolysis and lipid, amino acid metabolism, and nucleotide metabolism.	Pb exposure at 10 and 30 μg/L during 7 days was associated with changes in microbiota and in glucose, lipid, amino acid, and nucleotide metabolism.
Lu et al. (2014) [45]	Metals (Arsenic)	10 ppm as sodium arsenite	The exposure dose is above the maximum allowable concentration of arsenic in food.	C57BL/6 mice	16S rRNA gene sequencing and MS–based metabolomics profiling.	The most abundant gut bacteria were Firmicutes (52.79%) and Bacteroidetes (41.57%), followed by Tenericutes (3%), Actinobacteria (0.18%), Cyanobacteria (0.023%), and Proteobacteria (0.0042%)	Altered gut bacteria were strongly linked to changes in the microbiota metabolites. These changes increase the risk of tissue dysfunctions that might lead to obesity, insulin resistance, and cardiovascular disease.
Catron et al. (2019) [29]	BPA, BPAF, BPB, BPF, and BPS	BPA (0, 0.2, 0.6, 1.7, 2.9, 5.7, 11.5, 23.0, or 45.0 μM), BPAF (0, 0.2, 0.6, 1.8, 5.2, 15.3, or 45.0 μM), BPB (0, 0.6, 1.7, 5.1, 15.0, or 44.0 μM), BPF (0, 0.2, 0.6, 1.8, 5.2, 15.3, or 45.0 μM), or BPS (0, 0.2, 0.6, 1.8, 5.2, 15.3, or 45.0 μM)	Dose based on zebrafish toxicity data available through the iCSS ToxCast dashboard and previous zebrafish studies.	Zebrafish	16S rRNA gene sequencing.	Exposure to all the tested concentrations of BPS resulted in non-detectable levels of the Neisseriaceae family. Increasing BPS concentrations were associated with increased abundances of Cryomorphaceae. Increasing BPA or BPF concentrations were associated with increased abundances of Chromatiaceae and decreased abundances of Neisseriaceae.	BPS, BPA, or BPF exposure led to structural microbiota disruption during early development at concentrations not related to evident developmental toxicity. Results show that microbiota is very useful for characterization of health effects associated with exposure to environmental chemicals.
Chen, et al. (2018) [30]	BPA	0, 2, and 20 μg/L	Environmental concentrations.	Zefrafish (Danio rerio)	16S rRNA gene sequencing.	Nano-TiO2 and BPA co-exposure led to altered composition of guy microbiota with increased Proteobacteria and Actinobacteria in males and females. Hyphomicrobium was the most abundant genus in males and females.	Co-exposure to nano-TiO 2 and BPA modifies gut microbiome dynamics, having toxicological effects on host health.
DeLuca et al. (2018) [46]	BPA	50 µg/kg bw	Lowest observed adverse effect level.	C57BL/6 mice	IMAC at Texas A&M University and triple quadrupole mass spectrometer coupled to LC.	Exposure to BPA increased mortality, disease activity, and scores of colonic inflammation colon after exposure to sodium dextran sulfate.	BPA exposure decreased microbiota metabolites derived from aromatic amino acids and associated with colon inflammation and inflammatory bowel disease.
Javurek et al. (2016) [31]	BPA	50 mg/kg bw	Environmental exposure.	California mice	16S rRNA gene sequencing.	BPA exposure increased growth of pathogenic bacteria (Bacteroides, Mollicutes, and Prevotellaceae, among others) associated with inflammatory bowel disease, metabolic disorders, and colorectal cancer. However, increased Bifidobacterium was also found after BPA exposure.	Gut microbiota disruption secondary to BPA exposure is associated with systemic effects, such as inflammatory bowel disease, metabolic disorders, and colorectal cancer.
Koestel et al. (2017) [47]	BPA	52.2 ± 19.3 ng/food can or 36.2 ± 18.6 ng/food can	BPA levels identified in cans of diet. Serum dog concentrations 2.2 ng/mL, similar to that which has been reported in humans.	Dogs	16S rRNA gene sequencing.	Exposure to high concentrations of BPA was associated with increased bicarbonate levels in plasma and with changes in fecal microbiota (increased Clostrididiaceae, Bacteroides spp., Clostridiales, Ruminococcus spp., Lachnospiraceae, Roseburia spp., Clostridium hiranonis, and Megamonas spp.).	Exposure to high concentrations of BPA was associated with decreased Bacteroides spp., which is related to reduction in bacterial bisphenol degradation. This increases active BPA available for absorption in the gut.
Lai et al. (2016) [48]	BPA	Unknown concentration (BPA content in contaminated diet)	n.a.	CD-1 mice	LC-MS/MS, 16S rRNA gene sequencing, and amplicon PCR.	BPA and high-fat diet promoted growth of Proteobacteria (indicator of dysbiosis). Increased Helicobacteraceae proliferation and reduced Firmicutes and Clostridia were found in exposed mice.	Exposure to BPA in the diet led to structural changes in gut microbiota similar to those induced by high-fat diet and high-sucrose diet.
Liu et al. (2016) [32]	BPA	2000 μg/L	Dose used to simulate environmental exposure for a short period of exposure.	Zebrafish	16S rRNA gene sequencing and amplicon PCR reaction.	BPA exposure significantly modified gut microbiota composition with increased CKC4 phylum in male and female zebrafish.	BPA exposure altered gut microbiota composition. Gut dysbiosis may be related to changes in lipid metabolism of the host (increased triglycerides in the muscle).
Malaise et al. (2017) [5]	BPA	50 µg/kg bw	Exposure dose is 100 times below the current NOAEL in mice. NOAEL= 5 mg/kg BW/day	Mice	16S rRNA gene sequencing and Real time PCR.	Perinatal oral exposure to 50 µg/kg BPA led to gut and systemic immune changes in post-natal day 45. These changes were linked to altered glucose sensitivity and secretion of IgA in feces and decreased fecal Bifidobacteria compared to mice in the control group. These effects appear before the infiltration with proinflammatory M1 macrophages in gonadal white adipose tissue that appears with aging, along with decreased insulin sensitivity (T1D) and weight gain.	The results explain the sequence of changes related to perinatal exposure to BPA which could also explain the development of metabolic diseases in adulthood (decreased insulin sensitivity and increased weight gain).
Reddivari et al. (2017) [49]	BPA	200 μg/kg bw	To ensure gestational and lactational exposure of pups, approximately 1/25 of the NOAEL dose.	Rabbits	16S rRNA gene sequencing.	BPA exposure induced significant decrease in Oscillospira and Ruminococcaceae and therefore in short-chain fatty acid production. BPA exposure also reduced fecal levels of short-chain fatty acid, and increased systemic lipopolysaccharide and gut permeability.	Perinatal exposure to BPA modified gut microbiota composition and decreased beneficial bacterial metabolites such as short-chain fatty acids. BPA exposure also increased chronic inflammation in colon and liver, and systemic lipopolysaccharides.
Xu et al. (2019) [33]	BPA	30 or 300 µg/kg bw	Based on human exposure (30 µg/kg) and median human blood (300 µg/kg) levels	Mice	16S rRNA gene sequencing and amplicon PCR reaction.	BPA exposure-induced changes in gut microbiome composition are a potential mechanism of immunomodulation and T1D development. BPA at 30 or 300 µg/kg increased Bacteroidetes, and 300 µg/kg increased Cyanobacteria and TM7. The 30 µg/kg dose decreased Proteobacteria, and 300 µg/kg decreased Firmicutes and Tenericutes. Females showed an increase in pro-inflammatory factors, while males showed an increase in anti-inflammatory immune factors.	Altered gut microbiota and inflammation risk factors for T1D development associated with BPA exposure were sex-dependent.
Xu et al. (2019) [6]	BPA	30 or 300 µg/kg bw	To accelerate Diabetes type I development (30 µg/kg bw) and alter the immunity (300 µg/kg bw).	Mice	16S rRNA gene sequencing and amplicon PCR reaction	Adult females showed a higher risk of T1D and increased immune responses. However, female offspring showed lower risk of T1D and a shift towards anti-inflammation. In contrast, BPA exposure had little impact on DT1 and immunity in male offspring.	BPA effects on the development of T1D were related to host age and gender. Changes in gut microbiota and inflammation are responsible for T1D in juvenile exposure. Decreased inflammation is responsible for attenuated T1D in males and female offspring exposed during the perinatal period.
Chen, et al. (2018) [50]	PCB126 and PCB153	1.0 μg/L	Concentration below the limit established by EPA.	Zefrafish	16S rRNA gene sequencing.	PCB126 exposure led to altered microbiota and deterioration of the intestinal and hepatic functions. PCB126 was associated with oxidative stress and with a sexual dysmorphic effect. Exposure to PCB126 was significantly associated with oxidative stress, and exposure to PCB153 was associated with lower body weight, higher hepatosomatic index in female zebrafish, but lower index value in exposed males PCB153.	Exposure to PCB126 showed a significant correlation between dysbiosis and fish health.
Cheng et al. (2018) [51]	PCBs	6 or 30 mg/kg	To study dose-dependent effect of xenobiotics on the expression of hepatic drug metabolizing enzymes.	C57BL/6 mice	16S rRNA sequencing, quantitative PCR, and UPLC-MS/MS	Exposure to 6 mg/kg PCBs greatly increased the bacteria related to the metabolism of bile acids. This was associated with increased bile acids in serum and small intestine content in a microbiota-dependent fashion. However, at 30 mg/kg PCBs, bile acid levels remained stable and were linked with increased hepatic flow transporters and ileal Fgf15.	Changes in microbiota promoted increase in taurine mediated by PCBs in the muricholic acids α and β conjugated with taurine in liver, large and small intestine.
Chi et al. (2019) [52]	PCB126	50 μg/kg bw	Dose environmentally relevant to concentrations historically reported in lake trout from the Great Lakes.	C57BL/6 mice	16S rRNA gene sequencing and qRT-PCR	Exposure to PCB126 induced gut dysbiosis (increased Firmicutes and Bacteroidetes and decreased Erysipelotrichia) as well as dyslipidemia and nonalcoholic fatty liver disease.	Exposure to low doses of PCB-126 in mice caused intestinal microbiota dysbiosis and multiple disorders in serum and liver.
Choi et al. (2013) [53]	PCB153, PCB138, and PCB180	150 µmol/kg	PCB content in contaminated food.	C57BL/6 mice	16S rRNA gene sequencing and PCR.	Exposure to PCBs in sedentary mice resulted in decreased abundance of Proteobacteria. Exercised mice showed a gut microbiome structure significantly different from sedentary mice. Exercise lessened PCB-induced changes in gut microbiome.	Exposure to PCBs promotes changes in gut microbiome, which can determine systemic toxicity. Physical exercise lessens changes in gut microbiome.
Kohl et al. (2015) [54]	PCB126	7.3 ng/g	The exposure concentration is below the maximum allowable concentration of PCBs in food.	Northern leopard frogs (L. pipiens)	16S rRNA gene sequencing	Tadpoles exposed to PCB126 maintained increased Fusobacteria (t = 2.95; df = 14; p = 0.01). Fusobacteria was a very small portion of the tadpole (average of control and treated with PCB: 0.008%) and control frog (0.3 ± 0.1%) gut communities. Frogs exposed to PCB126 during larval stage had a relative Fusobacterial abundance of 3.5 ± 1.4%.	Exposure to PCB126 results in changes in gut microbiota communities, which might affect health and fitness of the host.
Petriello et al. (2018) [55]	PCB126	1 μmol/kg	This dose produces plasma PCB 126 levels that mimic human exposures of dioxin-like pollutants.	Ldlr −/− mice	16S rRNA gene sequencing and regression modeling.	PCB126 reduced α diversity (p = 0.001) in the colon and increased the Firmicutes to Bacteroidetes ratio (p = 0.044). Quantifiable amounts of PCB126 in the colon, upregulation of Cyp1a1 gene expression, and increased indicators of gut inflammation were found in exposed mice.	PCB126 exposure altered gut microbiota and metabolism and resulted in gut and systemic inflammation.
Rude et al. (2019) [56]	PCBs	0.1, 1, or 6 mg/kg/day	FDA mandates tolerances of 0.2–3.0 ppm (200–3000 ng/g) for all foods.	Mice	qPCR and 16S rRNA gene sequencing.	PCB exposure resulted in epithelial permeability defects in the ileum and colon of juvenile mutated mice. PCB exposure also promoted intestinal inflammation dysbiosis in gut microbiota in juvenile mutated mice exposed to 1 mg/kg/d PCBs versus controls.	The results showed the interactions between PCBs and genetic susceptibility factors to impact individual risk.
Horiuchi et al. (2017) [57]	Phytoestrogen (S-equol)	20 mg/kg, 2 times/d	Doses based on previous studies of the possible benefits of S-equol on diabetes.	Mice	Immunochemistry. Insulin secretion assay. qRT-PCR.	Administration of S-equol resulted in reduction of the induction of blood glucose concentrations (p < 0.01 at 15 min, p < 0.01 at 30 min, p < 0.05 at 60 min, and p < 0.01 at 120 min)	Gut microbiota-produced S-equol induced β-cell growth in vivo and insulin secretion ex vivo. Administration of S-equol decreased Streptozotocin-induced hyperglycemia by promoting β-cell function.
Huang et al. (2018) [58]	Phytoestrogens (Genistein)	20 mg/kg bw	Dose physiologically relevant to obtain an accurate interspecies extrapolation.	Mice	16S rRNA gene sequencing and qRT-PCR.	Perinatal genistein exposure caused increased incidence of DT1 in female offspring. Fecal microbiota from female offspring at postnatal day 90 showed increased Enterobacteriales (suggesting a proinflammatory response). In contrast, perinatal genistein administration caused a shift in microbiota towards anti-inflammation in males at postnatal day 90.	Perinatal administration of genistein resulted in strongly sex-dependent changes in microbiota. T1D exacerbation in non-diabetic females was related to immunomodulatory mechanisms associated with an altered gut microbiota.
López et al. (2018) [59]	Phytoestrogens (Genistein)	3 mg/kg bw/day	Equivalent dose of 1.5 g of genistein per day for a 65 kg adult person, approximately.	C57BL/6 mice	16S rRNA gene sequencing and qRT-PCR.	Mice fed with a high-fat diet with genistein exhibited changes in the gut microbiota linked to lower circulating levels of lipopolysaccharides, improved glucose metabolism, and reduced expression of pro-inflammatory cytokines in the liver compared to mice in the high-fat diet alone group.	Genistein exposure through diet can modulate gut microbiota, decreasing metabolic endotoxemia and neuroinflammatory response despite consumption of a high-fat diet.
Marshall et al. (2019) [60]	Phytoestrogens (Genistein)	250 mg/kg	The dose is above the maximum allowable concentration of genistein in food. EFSA LOAEL of 35 mg/kg bw/day for males and 44 mg/kg bw/day for females	California mice	GC/MS, 16S rRNA sequencing Social behavior testing using the three-chamber test	When male offspring from genistein-supplemented dams were compared with genistein-free offspring, audible calls above 20 kHz correlated with daidzein, α-tocopherol, Flexispira spp., and Odoribacter spp. Results suggest that early genistein exposure can induce a disruption in the offspring’s normal socio-communicative behaviors.	Perinatal exposure to genistein may detrimentally affect the offspring “microbiome-gut-brain axis”.
Piccolo et al. (2017) [61]	Phytoestrogens	Phytoestrogens naturally present in diet (pigs fed with soy-based infant formula)	Food exposure levels.	White Dutch Landrace pigs	16S rRNA gene sequencing and LC-MS.	Sow-fed piglets exhibited higher α-diversity in the duodenum than formula-fed piglets (p < 0.05). No differences were found in the ileum. Firmicutes was the most abundant phylum in the duodenum in all tested diets, followed by Proteobacteria in the sow-and milk-fed piglets and Cyanobacteria in soy-fed piglets.	Neonatal diet can impact small intestine microbiome in pigs, resulting in disturbances in the metabolism and development of intestinal tissue in the postnatal period.
Williams et al. (2019) [62]	Phytoestrogens	Phytoestrogens naturally present in diet	Food exposure levels.	Southern white rhinoceros (Ceratotherium simum simum)	16S rRNA amplicon sequencing and MS.	Composition and structure of fecal microbiota significantly differs by rhino species as well as at the phylum, family, and OUT levels.	Results suggest differences in receptor sensitivity to phytoestrogens related to the species and metabolism of dietary phytoestrogens by gut microbiota might have an impact on fertility of captive female rhinos.
Yeruva et al., (2016) [63]	Phytoestrogens	Phytoestrogens naturally present in diet (pigs were fed soy or milk formula).	Food exposure levels.	White Dutch, Landrace Duroc pigs	16S rRNA amplicon sequencing, qRT-PCR, ELISA and UHPLC-HRAM.	In soy-fed piglets, increased Lactobacillaceae spp. and Clostria spp. but decreased Enterobacteriaceae spp. were observed.	Neonatal diet promotes disturbances in microbiome of the small intestine in pigs, particularly in the duodenum.
Zhou et al. (2018) [64]	Phytoestrogens (Genistein)	0.25 and 0.6 g/kg	To analyze the effects of low and high exposure doses.	C57BL/6 mice	Oral glucose tolerance tests, ELISA kit, and 16S rRNA amplicon sequencing.	Perinatal maternal consumption of a high-fat diet with genistein resulted in increased birth weight, improved glucose tolerance and decreased fasting insulin, as well as lower levels of triacylglycerol and total cholesterol in serum in the offspring.	The intake of genistein during pregnancy improves the metabolism of the offspring, preventing the transgenerational effects of maternal high-fat diet on diabetes.
Obadia et al. (2018) [65]	Methylparaben (MPB)	0.0, 0.1, 0.2, and 0.3%	High levels of MPB (∼ 0.5%) can affect the microbiota diversity; the exposure dose was selected to test lower levels.	Drosophila melanogaster	-	Concentrations > 0.1% MPB disrupt the growth of some species of yeast and Acetobacter, but even at 0.3% Lactobacilli growth was less affected.	Exposure to MPB probably alters the composition and amount of gut bacteria and yeasts in laboratory fly.
Hu et al. (2016) [66]	Diethyl phthalate (DEP), methylparaben (MPB), triclosan (TCS) and their mixture (MIX)	0.050 mg TCS/kg bw, 0.1050 mg MPB/kg bw and 0.1735 mg DEP/kg bw	NOAEL.	Sprague-Dawley rats	16S rRNA gene sequencing and PCR.	Exposure to these chemicals produced an increase in Bacteroidetes (Prevotella) and decreased Firmicutes (Bacilli) in all the exposed rats. Increased Elusimicrobia was found in DEP and MPB exposed rats, Betaproteobacteria in MPB and MIX exposed rats, and Deltaproteobacteria in the TCS group. In adulthood, these differences decreased between cases and controls despite continued exposure, suggesting that contaminant exposure have a greater impact on gut microbiome of adolescent rats.	Exposure at doses similar to environmental human exposure can disturb the gut microbiota in adolescent rats. This disturbance mainly affects the health of the youngest.
Fan et al. (2020) [67]	Di (2-ethylhexyl)-phthalate	0.2, 2, and 20 mg/kg/day	Based on the EPA reference dose and previous studies.	Mice	LC-HRMS, 16S rRNA gene sequencing, and qPCR.	Prenatal exposure to low doses of di (2-ethylhexyl) phthalate (0.2 mg/kg/day) resulted in metabolic syndrome and gut dysbiosis. Thiamine liver metabolism was disrupted in the offspring, which caused disturbances in glucose metabolism.	Exposure to low doses of di (2-ethylhexyl) phthalate during the early stages of life might increase the risk of obesity and metabolic syndrome.
Lei et al. (2019) [37]	Di (2-ethylhexyl)-phthalate	1 or 10 mg/kg bw/day	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.	Oral probe di (2-ethylhexyl) phthalate exposure increased the abundance of Lachnoclostridum, while decreasing Akkermansia, Odoribacter, and Clostridium sensu stricto.	Di (2-ethylhexyl) phthalate exposure directly alters microbiota therefore modifying the production of bacterial metabolites related to neurodevelopmental disorders.
Gao et al. (2017) [68]	Diazinon	4 mg/L	According to previous studies, dose that did not elicit discernible AChE inhibition.	C57BL/6 mice	16S rRNA gene sequencing and mass spectrometry–based metabolomics.	Diazinon exposure significantly disturbed the intestinal microbiome, and the RNA sequencing revealed that diazinon exposure disrupts the functional metagenome. These changes were more pronounced male mice.	Diazinon exposure disturbed the structure of the gut microbiome, the functional metagenome and also had a sexual dysmorphic effect.
Jin et al. (2015) [69]	Carbendazim	100 or 500 mg/kg bw	The exposure concentration is above the maximum allowable concentration of carbendazim in food.	ICR mice (Mus musculus)	Real time PCR sequencing and 16s rRNA gene sequencing and HPLC.	Carbendazim exposure at 100 and 500 mg kg led to histopathological changes in the liver, disturbed lipid metabolism, and intestinal gut dysbiosis. During the first three days of exposure to carbendazim the most abundant constituents of microbiomes, Firmicutes and Bacteroidetes, tend to decrease. From the fifth day of treatment with carbendazim, Bacteroidetes maintained the decreasing tendency, but Firmicutes started to increase.	Exposure to carbendazim disturbs microbiota and can lead to inflammation, which results in altered lipid metabolism and triggers obesity in exposed mice.
Liang et al. (2019) [70]	Chlorpyrifos	5 mg/kg	Concentration higher than NOAEL.	C57Bl/6 and CD-1 mice	16S rRNA gene sequencing and qPCR.	Exposure to chlorpyrifos in mice induced changes in microbiota, increased body weight, and lowered insulin sensitivity. Chlorpyrifos also resulted in disruption of the intestinal barrier and more, which led to the entry of lipopolysaccharides in the body, which promote the release of pro-inflammatory factors.	Chlorpyrifos exposure might contribute to the worldwide epidemic of inflammatory diseases.
Liu et al. (2017) [71]	p, p’-dichlorodiphenyldichloroethylene (p, p’-DDE) and β-hexachlorocyclohexane (β-HCH)	1 mg p, p’-DDE/kg bw/day and 10 mg β-HCH/kg bw/day	These doses mimic the chronic exposure in human.	C57BL/6 mice	16S rRNA gene sequencing, real time PCR and UPLC-M.	Exposure to organochlorines disturbed the abundance and composition of gut microbiota (increased Lactobacillus capable of deconjugating bile salts). This affects the hydrophobicity and composition of bile acids, down-regulates the expression of genes involved in the reabsorption of bile acids in the distal ileum, and up-regulates the expression of genes involved in the hepatic synthesis of bile acids.	Chronic exposure to low doses of organochlorines increases the risk of dysfunction in bile acid metabolism.
Tu et al. (2019) [72]	2,4-Dichlorophenoxyacetic acid (2, 4-D)	< 15 mg/kg bw/day	Concentration lower than NOAEL.	C57BL/6 mice	16S rRNA gene sequencing and LC-MS.	Metagenomic results revealed a distinct intestinal microbiota with changes in various microbial metabolic pathways, including urea degradation, and amino acid and carbohydrate metabolism.	2,4-D exposure resulted in changes in the composition and activity of gut microbiota. The metabolic profile of host plasma samples showed changes in the metabolic profiles indicative of 2,4-D toxicity at low doses.
Yang et al. (2019) [73]	Organophosphorus: diethyl phosphate (DEP)	0.08 or 0.13 mg/kg	1/500 LD50.	Wistar rats	NanoDrop spectrophotometer and 16S rRNA gene sequencing.	Exposure to high dose of DEP promotes the growth of butyrate-producing bacterial genera Alloprevotella and Intestinimonas, which induced an increase in estradiol and a decrease in total triglycerides and low density lipoprotein cholesterol. Exposure to DEP also increased tyrosine-tyrosine peptide and ghrelin, attributed to the enrichment of Clostridium sensu stricto 1 and Lactobacillus, producers of short-chain fatty acids.	Chronic exposure to DEP affected the gut microbiota, serum hormones, and proinflammatory cytokines in rats, with stronger responses observed at high doses.
Wu et al. (2018) [74]	Propamocarb	0, 0.5, 5, 50 mg/kg bw/day	Dosages set according to the highest residue from the EU-MRLs and the NOAEL or long term toxicity.	Mice	16S rRNA gene sequencing.	Exposure to propamocarb disturbed the transcription of liver genes related to regulation of lipid metabolism. The microbiota in the cecal content and feces changed at the phylum or gender level.	Exposure to high dose propamocarb changes the metabolism of mice by altering the gut microbiota and microbial metabolites.
Gao et al. (2017) [75]	Triclosan (TCS)	2 ppm	The concentration used is 100 times lower than that which can promote liver carcinogenesis.	C57BL/6 mice	16S rRNA gene sequencing and shotgun metagenomics sequencing.	Exposure to TCS produced significant changes in mouse gut bacterial community assembly. Metagenomic sequencing showed an increase in gut bacterial genes related to triclosan resistance, stress response, and antibiotic resistance, and others.	Exposure to TCS alters the intestinal microbiome of mice by inducing changes at the compositional and functional levels.
Gaulke et al. (2016) [76]	TCS	100 μg/g	Dose to cause endocrine disruption in fish.	Zebrafish	16S rRNA gene sequencing.	Operational taxonomic units of the Enterobacteriaceae family are susceptible to TCS exposure, but operational taxonomic units of the Pseudomonas genus are more resistant to exposure.	Exposure to TCS promotes changes in the composition and ecological dynamics of gut microbial communities.
Kennedy et al. (2016) [77]	TCs (TCS and Triclocarban (TCC))	0.1% (v/v)	According to blood human level.	Timed-pregnant Sprague Dawley (SD) rats	16s rRNA gene sequencing.	TCC exposure reduced the diversity of fecal microbiota in exposed rats versus controls at 7 days after exposure. This continued throughout perinatal exposure.	α-diversity was reduced in exposed animals at all sampling time points after baseline. Differences in β-diversity were found between gestational day 18 and post-delivery day 16 in exposed versus control dams.
Ma et al. (2020) [78]	TCS	0, 10, or 50 mg/kg	Doses referenced previous toxicity studies in rats (Lowest toxic dose in rats is 50 mg/kg/day)	Rats	16S rRNA gene sequencing.	Exposure to TCS reduced diversity and altered the microbiota composition at doses of 50 mg/kg/day in adult rats and at two doses in old rats. These changes were long-lasting even after the exposure was terminated and accumulated over time, inducing metabolic disorders in old rat offspring.	Exposure to TCS early in life results in long-lasting changes in the metabolism and intestinal microbiota and they accumulate over time.
Narrowe et al. (2015) [79]	TCS	100 to 1000 ng/l	Environmentally relevant concentrations	Larval fathead minnows (Pimephales promelas)	High-throughput 16S rRNA sequencing	TCS resulted in an increase of all members of the order Pseudomonadales, in five Acinetobacter OTUs, and in 26 OTUs (Flavobacterium, Chryseobacterium, and Shewanella) at day 7.	Short-term, low-level environmental exposure to TCS is sufficient to disrupt gut microbiome in minnows.
Zang et al. (2019) [80]	TCS	0.002% (v/v)	Based on previous studies	Zebrafish (Danio rerio)	16S rRNA gene sequencing and qRT-PCR	TCS exposure led to severe structural and morphologic damage to the intestines, spleen, and kidney observed in histopathologic studies. Lactobacillus was able to mitigate this damage.	Lactobacillus plantarum ST-III increases gut microbial biodiversity in zebrafish and mitigates the damages associated with TCS exposure.

NOAEL: no observed adverse effects level; LOAEL: lowest observed adverse effect level; MRL: maximum residues levels.