Table 1.

Bisphenols and the Gut Microbiome

Chemical	Exposure Window	Dose	Model	Sex & Sex Differences	Effect on Gut Microbiota	Conclusions	References
BPA	Developmental	0, 0.2, 0.6, 1.7, 2.9, 5.7, 11.5, 23.0, or 45.0 µM in water environment	Zebrafish embryo	Not applicable	↑ Chromatiaceae ↓ Neisseriaceae (−) Rheinheimera, Pseudomonas, Leptothrix	High variability between vehicle control groups in each experiment BPA and BPF caused similar microbial community changes	Catron et al. (2019)
		50 µg/kg bw dams dosed orally from GD 15 to weaning	Mice	Male offspring	↓ Bifidobacterium ↑ Bacteroidetes	BPA acted as an obesogen, induced inflammation, and altered immune responses Supports link between alterations in the gut microbiome and metabolic disease	Malaise et al. (2017)
		50 µg/kg bw dams dosed orally from GD 15 to weaning	Mice	Female offspring	Not applicable	BPA exposure induced defects in fecal antimicrobial activity and impaired protection of the gut BPA treatment altered the gut-associated immune system and systemic immune response	Malaise et al. (2018)
		200 µg/kg bw dams dosed orally from GD 15 to PND 7	Rabbits	Male offspring	↓ Bacteroidetes ↓ Ruminococcaceae ↓ Oscillospira (dams)	BPA-induced colonic and liver inflammation BPA altered the colonic metabolome	Reddivari et al. (2017)
		50 mg/kg feed weight (approximately 10mg/kg bw) F0 dams exposed through chow 2 weeks before mating through PND 30 (weaning), F0 males exposed breeding through weaning	Mice	Both; yes	↑ Mogibacteriaceae, Sutterella spp., and Clostridiales in F0 females ↑ Mollicutes and Prevotellaceae compared in F0 males ↑ Bifidobacterium, Mogibacteriaceae in F1 females ↑ Akkermansia, Methanobrevibacter in F1 males	BPA exposure causes some of the same effects on the gut as ethinylestradiol (EE) exposure and some unique effects compared with EE Clear sex differences in the effects of BPA were evident in both generations BPA-mediated changes in the gut microbiota were inversely related to specific amino acid, lipid, and xenobiotic metabolism/degradation in females BPA-mediated changes in the gut were positively associated with changes in sulfur metabolism, insulin signaling pathway, and steroid hormone biosynthesis in males	Javurek et al. (2016)
	Juvenile	30 µg/kg BW gavaged from PND 28 to 56	Nonobese diabetic mice	Female	↑ Verrucomicrobia ↓ Nitrospira, OD1, AD3, and Gemmatimonadetes	Bacterial alterations correlated with blood glucose levels and immune endpoints	Xu et al. (2019)
	Adult	0, 2, and 20 µg/L and 2 or 20 µg/L BPA + 100 µg/l nano-TiO2 in water environment for 3 months	Zebrafish	Both; yes	↑ Actinobacteria at 2 µg/L ↑ Lawsonia ↓ Hyphomicrobium	Coexposure to TiO2 antagonized BPA effects at the low dose and synergized at the high dose Similar microbiome effects of BPA in both sexes Serotonin levels in the gut were decreased in BPA-exposed males Changes in gut microbes related to oxidative stress	Chen et al. (2018b)
		12–18 µg/kg feed weight in dog food contaminated with BPA can lining, 14 days	Dogs, gonadectomized	Both; yes but small n	↓ Bacteroides spp., Streptophyta, Erysipelotrichaceae, and Flexispira spp ↑ Bacteroides ovatus, [Prevotella spp.], [Ruminococcus spp.], and Cetobacterium somerae	Exposure to BPA led to an increase in serum BPA levels Some diet by sex interactions observed, but hard to interpret with small sample size Bacteria known to metabolize bisphenols were suppressed with BPA treatment	Koestel et al. (2017)
		2000 µg/L in water environment for 5 weeks	Zebrafish	Male, age not specified	BPA altered microbial community; no analysis of statistical significance between groups	BPA exposure caused similar changes in the gut as EE Untreated male and female zebrafish have similar gut microbiota	Liu et al. (2017)
	In vitro	0–400 µM for 24 h	HCT116 human colon cancer cells	Not applicable	Not applicable	BPA treatment decreased cell viability, caused oxidative damage due to ROS accumulation, disrupted mitochondrial function, and promoted apoptosis	Qu et al. (2018)
		25, 250, and 2500 µg/L in nutritional medium for 10 days	In vitro Simulator of the Human Intestinal Microbial Ecosystem	Not applicable	BPA ↓ microbial community richness at low doses and increased it at high dose; no analysis of statistical significance between groups ↑ Microbacterium and Alcaligenes	BPA exposure increased genes related to oxidative stress and altered expression of estrogen receptors BPA is metabolized in the system	Wang et al. (2018b)
		0–400 µM for 24 h	LS174T human colonic goblet cells	Not applicable	Not applicable	BPA affected the secretory function of intestinal goblet cells by inducing mitochondrial dysfunction, oxidative stress, and apoptosis	Zhao et al. (2018)
Other bisphenols	Developmental	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, 45.0 µM), BPS (0, 0.2, 0.6, 1.8, 5.2, 15.3, 45.0 µM) in water environment for 10 days	Zebrafish embryo	Not applicable	↓ Neisseriaceae (BPS) ↑ Cryomorphaceae (BPS) ↑ Chromatiaceae (BPF) ↓ Neisseriaceae (BPF)	Exposure to the least developmentally toxic bisphenols impacted microbiota the most (BPS, BPA, BPF); the most developmentally toxic bisphenols did not impact microbiota (BPB, BPAF) Similar microbial changes for BPA and BPF exposure, unique profile for BPS exposure High variability between vehicle control groups in each experiment	Catron et al. (2019)