The human gut chemical landscape predicts microbe-mediated biotransformation of foods and drugs

Abstract

Microbes are nature’s chemists, capable of producing and metabolizing a diverse array of compounds. In the human gut, microbial biochemistry can be beneficial, for example vitamin production and complex carbohydrate breakdown; or detrimental, such as the reactivation of an inactive drug metabolite leading to patient toxicity. Identifying clinically relevant microbiome metabolism requires linking microbial biochemistry and ecology with patient outcomes. Here we present MicrobeFDT, a resource which clusters chemically similar drug and food compounds and links these compounds to microbial enzymes and known toxicities. We demonstrate that compound structural similarity can serve as a proxy for toxicity, enzyme sharing, and coarse-grained functional similarity. MicrobeFDT allows users to flexibly interrogate microbial metabolism, compounds of interest, and toxicity profiles to generate novel hypotheses of microbe-diet-drug-phenotype interactions that influence patient outcomes. We validate one such hypothesis experimentally, using MicrobeFDT to reveal unrecognized gut microbiome metabolism of the ovarian cancer drug altretamine.

Fucoidans: Downstream Processes and Recent Applications

“…Novel innovative purification techniques were recently developed, such as selective solid phase extraction for purifying fucoidans and other complex seaweeds polymers by molecularly imprinted polymers (MIP) [142,143] or MIP modified by deep eutectic solvents [142,143]. Abdella et al, developed a green and time-saving purification protocol using genipin cross-linked toluidine blue immobilized-chitosan beads employing fucoidans affinity to cationic thiazine dyes [102].…”

In sickness and health: Effects of gut microbial metabolites on human physiology

“…Some of the findings described previously can be leveraged to design tools to guide drug selection and therapeutic interventions. A recently developed in silico tool is being used to model interactions between drug classes and bacterial enzymes with activities against these drugs [63]. This approach was used to successfully predict 3 previously unknown xenobiotic metabolic pathways by gut microbes that were confirmed through in vitro studies [63].…”

“…A recently developed in silico tool is being used to model interactions between drug classes and bacterial enzymes with activities against these drugs [63]. This approach was used to successfully predict 3 previously unknown xenobiotic metabolic pathways by gut microbes that were confirmed through in vitro studies [63]. As knowledge of microbiome-drug interactions expands, it is likely that future personalized medicine approaches will use these predictive tools coupled with in vitro and in vivo models to guide treatment regimes in a myriad of diseases.…”

Colonic Bacteria-Transformed Catechin Metabolite Response to Cytokine Production by Human Peripheral Blood Mononuclear Cells

“…The gut microbe produces a larger toolkit of enzymes that catalyze the diverse range of chemical reactions and results in transformation of catechin. However, this alteration can cause increase or decrease the activity on human health [15]. The aim of the present study was to investigate in vitro microbial biotransformation and the effect of biotransformed metabolites on the proliferation of human peripheral blood mononuclear cells (PBMCs), specifically the production of pro-inflammatory cytokines and anti-inflammatory cytokine profiles such as IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17A, interferon gamma (IFN-γ), transforming growth factor-β, (TGF-β), tumor necrosis factor-β (TNF-β), and GM-CSF.…”