Table 1.

The influence of gut microbiota on bioavailability of oral drugs.

Possible mechanism	Name	Therapeutic application	The influence on PK or pharmacological effects of the drug	Ref.
Prodrugs are metabolized by the gut microbiota	Prontosil	Antibacterial drug	Activate the drug and the bioavailability is decreased when pretreated with antibiotics	30, 31
	Sulfasalazine	Antibacterial drug	Activate the drug and the bioavailability is decreased when pretreated with antibiotics	32
	Lovastatin	Lipid-lowering drug	The bioavailability and pharmacological effects are decreased when antibiotics are used	33
The gut microbiota participates in its first-pass effect	Deleobuvir	Antiviral drug	Plasma exposure of its major metabolite, CD 6168, is decreased substantially in pseudo-germ free rats	24
	Amlodipine	Cardiovascular drug for hypertension	The systemic exposure of amlodipine is decreased	34
	Nifedipine	Cardiovascular drug for hypertension	The bioavailability of nifedipine is increased when antibiotics are used or in the hypoxic condition	35
	Aspirin	Non-steroidal anti-inflammatory drug	The bioavailability of aspirin is increased when antibiotics are used or after the quick ascent to the plateau	36, 37, 38
Microbial β-glucuronidases participate in the enterohepatic recirculation	Mycophenolic acid	Immunosuppressant	AUC0–12 h of the mycophenolic acid is decreased while CL of it is increased when pretreated with antibiotics	39
	Indomethacin	Non-steroidal anti-inflammatory drug	The half-time is shortened and drug's systemic exposure is reduced when pretreated with antibiotics	25
The drug transport is affected by the modulations of bile acids induced by the gut microbiota	Simvastatin	Lipid-lowering drug	Enhanced plasma concentration of simvastatin is positively correlated with increased levels of several secondary bile acids	40
	Lovastatin	Lipid-lowering drug	NaDC containing formulations have better bioavailability of lovastatin than NaGC containing solid dispersions	41
The expression of drug transporters is affected by the gut microbiota or the compounds derived from the gut microbiota	Ascorbic acid	Antioxidant	The absorption of ascorbic acid is decreased by LPS generated from the gut microbiota	26
	Glycyrrhizic acid	Liver protective drug	The bioavailability of glycyrrhizic acid is increased by the supplements of Lactobacillus murinus	42
Eggerthella lenta possessing cgr operon converts digoxin into dihydrodigoxin	Digoxin	Cardiovascular drug for heart failure and atrial fibrillation	Inactivate digoxin	43, 44, 45, 46, 47
Berberine is converted into dihydroberberine by the gut microbial nitroreductases	Berberine	Treatment for diarrhea, hyperlipidemia and type 2 diabetes	The absorption of berberine is facilitated	48
The infection of Helicobacter pylori However, the exact mechanisms remain unknown	Levodopa	Treatment for Parkinson's disease	The absorption and therapeutic efficacy of levodopa are impaired by the Helicobacter pylori infection	28,49, 50, 51
The state of hepatic sulphate can be influenced by the gut microbiota	Acetaminophen	Non-steroidal anti-inflammatory drug	The AUC of acetaminophen is higher in pseudo germ-free rats compared with control rats	52

AUC, the area under the curve; CL, clearance; LPS, lipopolysaccharide; NaDC, sodium deoxycholate; NaGC, sodium glycholate; PK, pharmacokinetics.