The influence of the gut microbiota on the bioavailability of oral drugs

Abstract

Due to its safety, convenience, low cost and good compliance, oral administration attracts lots of attention. However, the efficacy of many oral drugs is limited to their unsatisfactory bioavailability in the gastrointestinal tract. One of the critical and most overlooked factors is the symbiotic gut microbiota that can modulate the bioavailability of oral drugs by participating in the biotransformation of oral drugs, influencing the drug transport process and altering some gastrointestinal properties. In this review, we summarized the existing research investigating the possible relationship between the gut microbiota and the bioavailability of oral drugs, which may provide great ideas and useful instructions for the design of novel drug delivery systems or the achievement of personalized medicine.

Keywords: 5-ASA, 5-aminosalicylic acid; AA, ascorbic acid; ABC, ATP-binding cassette; ACS, amphipathic chitosan derivative; AMI, amiodarone; AQP4, aquaporin 4; AR, azoreductase; ASP, amisulpride; BBR, berberine; BCRP, breast cancer resistance protein; BCS, biopharmaceutics classification system; BDDCS, the biopharmaceutics drug disposition classification system; BDEPT, the bacteria-directed enzyme prodrug therapy; BSH, bile salt hydrolase; Bioavailability; CA, cholic acid; CDCA, chenodeoxycholic acid; CPP, cell-penetrating peptide; CS, chitosan; Colon-specific drug delivery system; DCA, deoxycholic acid; DRPs, digoxin reduction products; EcN, Escherichia coli Nissle 1917; FA, folate; FAO, Food and Agriculture Organization of the United Nations; GCDC, glycochenodeoxycholate; GL, glycyrrhizic acid; Gut microbiota; HFD, high fat diet; HTC, hematocrit; IBD, inflammatory bowel disease; LCA, lithocholic acid; LPS, lipopolysaccharide; MATEs, multidrug and toxin extrusion proteins; MDR1, multidrug resistance gene 1; MDR1a, multidrug resistance protein-1a; MKC, monoketocholic acid; MPA, mycophenolic acid; MRP2, multidrug resistance-associated protein 2; NEC, necrotizing enterocolitis; NMEs, new molecular entities; NRs, nitroreductases; NSAIDs, non-steroidal anti-inflammatory drugs; NaDC, sodium deoxycholate; NaGC, sodium glycholate; OATs, organic anion transporters; OCTNs, organic zwitterion/cation; OCTs, organic cation transporters; Oral drugs; P-gp, P-glycoprotein; PD, Parkinson's disease; PPIs, proton pump inhibitors; PT, pectin; PWSDs, poorly water-soluble drugs; Probiotics; RA, rheumatoid arthritis; RBC, red blood cell; SCFAs, short-chain fatty acids; SGLT-1, sodium-coupled glucose transporter 1; SLC, solute carrier; SLN, solid lipid nanoparticle; SP, sulfapyridine; SSZ, sulfasalazine; SVCT-1/2, the sodium-dependent vitamin C transporter-1/2; T1D, type 1 diabetes; T1DM, type 1 diabetes mellitus; T2D, type 2 diabetes; TCA, taurocholate; TCDC, taurochenodeoxycholate; TDCA, taurodeoxycholate; TLCA, taurolithocholate; TME, the tumor microenvironment; UDC, ursodeoxycholic acid; WHO, World Health Organization; an OTC drug, an over-the-counter drug; cgr operon, cardiac glycoside reductase operon; dhBBR, dihydroberberine; pKa, dissociation constant; the GI tract, the gastrointestinal tract.