The human gut microbiome is a complex ecosystem that can mediate the interaction of the human host with their environment. The interaction between gut microbes and commonly used non-antibiotic drugs ...is complex and bidirectional: gut microbiome composition can be influenced by drugs, but, vice versa, the gut microbiome can also influence an individual's response to a drug by enzymatically transforming the drug's structure and altering its bioavailability, bioactivity or toxicity (pharmacomicrobiomics). The gut microbiome can also indirectly impact an individual's response to immunotherapy in cancer treatment. In this review we discuss the bidirectional interactions between microbes and drugs, describe the changes in gut microbiota induced by commonly used non-antibiotic drugs, and their potential clinical consequences and summarise how the microbiome impacts drug effectiveness and its role in immunotherapy. Understanding how the microbiome metabolises drugs and reduces treatment efficacy will unlock the possibility of modulating the gut microbiome to improve treatment.
The mammalian gut is colonized by trillions of microorganisms collectively called the microbiome. It is increasingly clear that this microbiome has a critical role of in many aspects of health ...including metabolism and immunity. While environmental factors such as diet and medications have been shown to influence the microbiome composition, the role of host genetics has only recently emerged in human studies and animal models. In this review, we summarize the current state of microbiome research with an emphasis on the effect of host genetics on the gut microbiome composition. We focus particularly on genetic determinants of the host immune system that help shape the gut microbiome and discuss avenues for future research.
A proportion of gut bacteria are heritable.
The impact of host genetics on the gut microbiome in humans is being revealed through genome-wide association studies.
The effect size of host genetics on the microbiome appears to be modest.
Several associations are found between the microbiome and genes associated with diet, innate immunity, vitamin D receptors, and metabolism.
A consistent genetic signal comes from pattern recognition receptor molecules, particularly C-type lectins.
The human gut microbiota has now been associated with drug responses and efficacy, while chemical compounds present in these drugs can also impact the gut bacteria. However, drug-microbe interactions ...are still understudied in the clinical context, where polypharmacy and comorbidities co-occur. Here, we report relations between commonly used drugs and the gut microbiome. We performed metagenomics sequencing of faecal samples from a population cohort and two gastrointestinal disease cohorts. Differences between users and non-users were analysed per cohort, followed by a meta-analysis. While 19 of 41 drugs are found to be associated with microbial features, when controlling for the use of multiple medications, proton-pump inhibitors, metformin, antibiotics and laxatives show the strongest associations with the microbiome. We here provide evidence for extensive changes in taxonomy, metabolic potential and resistome in relation to commonly used drugs. This paves the way for future studies and has implications for current microbiome studies by demonstrating the need to correct for multiple drug use.
By a simple electrodeposition process for surface roughening and a facile immersion process for chemical modification, Cu-Cu-DA/SH superhydrophobic and oleophilic film is realized on copper mesh, and ...acts a tool to separate oil-water mixtures effectively and quickly.
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•Dopamine assisted 1-dodecanethiol film on rough mesh was prepared.•The film exhibited superhydrophobicity and oleophilicity.•The film showed high oil flux and oil-water separation efficiency.•The preparation processes were simple and low-cost.
A superhydrophobic and oleophilic copper mesh film with micro/nano hierarchical structures was prepared through facile electrodeposition and immersion processes. Contact angles of water and oil on the modified mesh were 152.4° and 12.6°, respectively. The modified mesh showed high oil-water separation efficiency (were above 90%) and rate with high oil flux of 4507Lm−2h−1. Results show that oil can pass through the coated mesh easily, whereas water was held on the modified mesh, which demonstrated that the coated films matched well with the requirements for effective separation of oil-water mixtures. Therefore, the coated mesh is a promising and effective membrane for separating oil-water mixtures.
By following up the gut microbiome, 51 human phenotypes and plasma levels of 1,183 metabolites in 338 individuals after 4 years, we characterize microbial stability and variation in relation to host ...physiology. Using these individual-specific and temporally stable microbial profiles, including bacterial SNPs and structural variations, we develop a microbial fingerprinting method that shows up to 85% accuracy in classifying metagenomic samples taken 4 years apart. Application of our fingerprinting method to the independent HMP cohort results in 95% accuracy for samples taken 1 year apart. We further observe temporal changes in the abundance of multiple bacterial species, metabolic pathways, and structural variation, as well as strain replacement. We report 190 longitudinal microbial associations with host phenotypes and 519 associations with plasma metabolites. These associations are enriched for cardiometabolic traits, vitamin B, and uremic toxins. Finally, mediation analysis suggests that the gut microbiome may influence cardiometabolic health through its metabolites.
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•Gut microbial genetic stability differs across species•Gut microbial composition with higher baseline diversity is more stable over time•Individual-specific, temporally stable microbial profiles can fingerprint the host•The microbial impact on host health is mediated by plasma metabolites
A longitudinal analysis of 338 individuals across 4 years characterizes the temporal stability and diversity of human gut microbiome, linking the microbial profile with individual-specific host phenotypes and suggesting the role of plasma metabolites in mediating the impact of microbiome on host physiology.
Gut microbiome and bile acids in obesity-related diseases Li, Rumei; Andreu-Sánchez, Sergio; Kuipers, Folkert ...
Baillière's best practice and research in clinical endocrinology and metabolism/Baillière's best practice & research. Clinical endocrinology & metabolism,
05/2021, Volume:
35, Issue:
3
Journal Article
Peer reviewed
Open access
Dysbiosis has been implemented in the etiologies of obesity-related chronic diseases such as type 2 diabetes, NAFLD and cardiovascular diseases. Bile acids, a class of amphipathic steroids produced ...in the liver and extensively modified by the microbiome, are increasingly recognized as actors in onset and progression of these diseases. Indeed, human obesity is associated with altered bile acid metabolism. Bile acids facilitate intestinal fat absorption but also exert hormone-like functions through activation of nuclear and membrane-bound receptors and thereby modulate glucose, lipid and energy metabolism, intestinal integrity and immunity. Bile acid-signaling pathways have thus been identified as potential pharmacological targets for obesity-related diseases. Interfering with microbiome composition may also be considered, as liver- and microbiome-derived bile acid species have different signaling functions. This review summarizes recent developments in this rapidly expanding field of research and addresses potential clinical prospects of interference with bile acid signaling pathways in human diseases.
The human gut harbors a complex ecosystem of microorganisms, including bacteria and viruses. With the rise of next-generation sequencing technologies, we have seen a quantum leap in the study of ...human-gut-inhabiting bacteria, yet the viruses that infect these bacteria, known as bacteriophages, remain underexplored. In this review, we focus on what is known about the role of bacteriophages in human health and the technical challenges involved in studying the gut virome, of which they are a major component. Lastly, we discuss what can be learned from studies of bacteriophages in other ecosystems.
Gut microbiota has been implicated in major diseases affecting the human population and has also been linked to triglycerides and high-density lipoprotein levels in the circulation. Recent ...development in metabolomics allows classifying the lipoprotein particles into more details. Here, we examine the impact of gut microbiota on circulating metabolites measured by Nuclear Magnetic Resonance technology in 2309 individuals from the Rotterdam Study and the LifeLines-DEEP cohort. We assess the relationship between gut microbiota and metabolites by linear regression analysis while adjusting for age, sex, body-mass index, technical covariates, medication use, and multiple testing. We report an association of 32 microbial families and genera with very-low-density and high-density subfractions, serum lipid measures, glycolysis-related metabolites, ketone bodies, amino acids, and acute-phase reaction markers. These observations provide insights into the role of microbiota in host metabolism and support the potential of gut microbiota as a target for therapeutic and preventive interventions.
Microbiome-wide association studies on large population cohorts have highlighted associations between the gut microbiome and complex traits, including type 2 diabetes (T2D) and obesity
. However, the ...causal relationships remain largely unresolved. We leveraged information from 952 normoglycemic individuals for whom genome-wide genotyping, gut metagenomic sequence and fecal short-chain fatty acid (SCFA) levels were available
, then combined this information with genome-wide-association summary statistics for 17 metabolic and anthropometric traits. Using bidirectional Mendelian randomization (MR) analyses to assess causality
, we found that the host-genetic-driven increase in gut production of the SCFA butyrate was associated with improved insulin response after an oral glucose-tolerance test (P = 9.8 × 10
), whereas abnormalities in the production or absorption of another SCFA, propionate, were causally related to an increased risk of T2D (P = 0.004). These data provide evidence of a causal effect of the gut microbiome on metabolic traits and support the use of MR as a means to elucidate causal relationships from microbiome-wide association findings.
Gut microbial dysbioses are linked to aberrant immune responses, which are often accompanied by abnormal production of inflammatory cytokines. As part of the Human Functional Genomics Project (HFGP), ...we investigate how differences in composition and function of gut microbial communities may contribute to inter-individual variation in cytokine responses to microbial stimulations in healthy humans. We observe microbiome-cytokine interaction patterns that are stimulus specific, cytokine specific, and cytokine and stimulus specific. Validation of two predicted host-microbial interactions reveal that TNFα and IFNγ production are associated with specific microbial metabolic pathways: palmitoleic acid metabolism and tryptophan degradation to tryptophol. Besides providing a resource of predicted microbially derived mediators that influence immune phenotypes in response to common microorganisms, these data can help to define principles for understanding disease susceptibility. The three HFGP studies presented in this issue lay the groundwork for further studies aimed at understanding the interplay between microbial, genetic, and environmental factors in the regulation of the immune response in humans.
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•Database of predicted gut microbial associations with human cytokine responses•Microbiome-host interactions modulate inflammatory cytokine production capacity•Cytokine responses are associated with microbial taxonomic and functional features•Microbial metabolites modulate pathogen-induced TNFα and IFNγ responses
As part of the Human Functional Genomics Project, this study investigates the relationship between the gut microbiome and inter-individual variation in cytokine responses in humans, providing a resource of predicted microbially derived mediators that influence immune phenotypes in response to common microorganisms.
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