Table 2.

Adverse effects/toxicities resulting from xenobiotic-microbiome interactions (pharmaceutical toxicomicrobiomic interactions).

Xenobiotic	Microbes	Effect	Reference
Carboplatin	Prevotella copri	In a rat model, carboplatin-induced intestinal mucositis was reduced after metronidazole treatment, which was intended to target the anaerobic P. copri.	(Yu et al., 2019)
Doxorubicin	Intestinal microbiota	The enteric microbiota was found to play a major role in doxorubicin-induced mucositis. Targeting the microbiota reduced damage.	(Rigby et al., 2016)
Irinotecan	Intestinal microbiota	Deconjugation of SN-38G (Irinotecan pharmacologically active derivative) in the gut by bacterial beta-glucuronidases resulted in gut toxicity.	(Takasuna et al., 1996)
5-Fluorouracil	Intestinal microbiota	Treatment with 5-FU was shown to cause significant changes in intestinal microbiota and mucin secretion in a rat model. These changes contributed to development of 5-FU-induced mucositis.	(Stringer et al., 2009)
Acetaminophen	Intestinal microbiota	Elevated levels of p-cresol (produced by some intestinal bacterial communities, which are not equally abundant in all individuals) compete with acetaminophen on the o-sulfonation metabolism, which results in increased acetaminophen toxicity.	(Clayton et al., 2009)
Sorivudine	Bacteroides	Sorivudine hydrolysis by intestinal anaerobic bacteria results in high blood concentration of 5-(E)-(2-bromovinyl)uracil increasing the level and toxicity of 5-fluorouracil during chemotherapy.	(Nakayama et al., 1997)
Cycasin	Intestinal microbiota	Cycasin hydrolysis by the gut microbiota resulted in a hepatotoxic and carcinogenic methylazoxymethanol.	(Spatz et al., 1967)
Indomethacin	Luminal bacteria	Interaction of the oral NSAID, indomethacin, with gut microbes resulted in damage to the intestinal mucosa.	(Basivireddy et al., 2005)
Nitrazepam	Clostridium leptum	Nitrazepam reduction by the clostridial nitroreductase enzyme was reported to caused teratogenic effects in pregnant women.	(Rafii et al., 1997)
Oxaliplatin	Intestinal microbiota	The gut microbiota is involved in oxaliplatin-induced mechanical hyperalgesia, which was shown to be reduced in germ-free mice and in mice pretreated with antibiotics.	(Shen et al., 2017)
L−carnitine	Intestinal microbiota	L-carnitine is metabolized by the gut microbiota to trimethylamine (TMA) which is further metabolized in the liver to produce the toxic metabolite TMA-N-oxide (TMAO) that increases the risk of atherosclerosis and cardiovascular diseases.	(Koeth et al., 2013)