Response to a drug often differs widely among individual patients. This variability is frequently observed not only with respect to effective responses but also with adverse drug reactions. Matching patients to the drugs that are most likely to be effective and least likely to cause harm is the goal of effective therapeutics. Pharmacogenomics (PGx) holds the promise of precision medicine through elucidating the genetic determinants responsible for pharmacological outcomes and using them to guide drug selection and dosing. Here we survey the US landscape of research programs in PGx implementation, review current advances and clinical applications of PGx, summarize the obstacles that have hindered PGx implementation, and identify the critical knowledge gaps and possible studies needed to help to address them.

To gain insight into the complex microbiome-gut-brain axis in irritable bowel syndrome (IBS), several modalities of biological and clinical data must be combined. We aimed to identify profiles of fecal microbiota and metabolites associated with IBS and to delineate specific phenotypes of IBS that represent potential pathophysiological mechanisms. Fecal metabolites were measured using proton nuclear magnetic resonance ( 1 H-NMR) spectroscopy and gut microbiome using shotgun metagenomic sequencing (MGS) in a combined dataset of 142 IBS patients and 120 healthy controls (HCs) with extensive clinical, biological and phenotype information. Data were analyzed using support vector classification and regression and kernel t-SNE. Microbiome and metabolome profiles could distinguish IBS and HC with an area-under-the-receiver-operator-curve of 77.3% and 79.5%, respectively, but this could be improved by combining microbiota and metabolites to 83.6%. No significant differences in predictive ability of the microbiome–metabolome data were observed between the three classical, stool pattern-based, IBS subtypes. However, unsupervised clustering showed distinct subsets of IBS patients based on fecal microbiome–metabolome data. These clusters could be related plasma levels of serotonin and its metabolite 5-hydroxyindoleacetate, effects of psychological stress on gastrointestinal (GI) symptoms, onset of IBS after stressful events, medical history of previous abdominal surgery, dietary caloric intake and IBS symptom duration. Furthermore, pathways in metabolic reaction networks were integrated with microbiota data, that reflect the host-microbiome interactions in IBS. The identified microbiome–metabolome signatures for IBS, associated with altered serotonin metabolism and unfavorable stress response related to GI symptoms, support the microbiota-gut-brain link in the pathogenesis of IBS.

Background: Taurine, 2-aminoethanesulfonic acid, is an amino acid found in animal products. Taurine is produced for human consumption as a supplement and ingredient in beverages. Supplementation is a safe, inexpensive, and effective treatment for dilated cardiomyopathy (DCM) in domestic mammals, however it is currently unlicensed in Europe and the United States for human medical treatment. Recent genome-wide association studies of DCM have identified the locus of the taurine transporter (SLC6A6). To assess whether taurine supplementation may be a novel therapeutic option for DCM, we undertook a systematic review. Methods: Four electronic databases (PubMed, Cochrane Central Register, Web of Science, Biomed Central) were searched until 11/03/21. Included studies of human participants reported measured phenotypes or symptoms for cardiomyopathy, heart failure (HF), or altered left ventricle structure or function, administering taurine in any formulation, by any method. Non-English articles were excluded. Meta-analysis was completed in R software (version 3.6.0). The Newcastle-Ottawa Scale quality assessment score (NOQAS) tool was used to assess bias. Results: 285 articles were identified, of which eleven met our criteria for inclusion. Only one paper was deemed “high quality” using the NOQAS tool. Taurine supplementation varied across studies; by dose (500 mg to 6g per day), frequency (once to thrice daily), delivery method (tablet, capsule, drink, powder), and duration (2 to 48 weeks). Patient inclusion was all-cause HF patients with ejection fraction (EF) <50% and no study was specific to DCM. While improvements in diastolic and systolic function, exercise capacity, and haemodynamic parameters were described, only EF and stroke volume were measured in enough studies to complete a meta-analysis; the association was not significant with all-cause HF (P<0.05). No significant safety concerns were reported. Conclusions: A formal clinical trial is needed to address whether taurine supplementation is beneficial to the approximately 1/250 individuals with DCM in the population.

Background: Taurine, 2-aminoethanesulfonic acid, is an amino acid found in animal products. Taurine is produced for human consumption as a supplement and ingredient in beverages. Supplementation is a safe, inexpensive, and effective treatment for dilated cardiomyopathy (DCM) in domestic mammals, however it is currently unlicensed in Europe and the United States for human medical treatment. Recent genome-wide association studies of DCM have identified the locus of the taurine transporter (SLC6A6). To assess whether taurine supplementation may be a novel therapeutic option for DCM, we undertook a systematic review. Methods: Four electronic databases (PubMed, Cochrane Central Register, Web of Science, Biomed Central) were searched until 11/03/21. Included studies of human participants reported measured phenotypes or symptoms for cardiomyopathy, heart failure (HF), or altered left ventricle structure or function, administering taurine in any formulation, by any method. Non-English articles were excluded. Meta-analysis was completed in R software (version 3.6.0). The Newcastle-Ottawa Scale quality assessment score (NOQAS) tool was used to assess bias. Results: 285 articles were identified, of which eleven met our criteria for inclusion. Only one paper was deemed “high quality” using the NOQAS tool. Taurine supplementation varied across studies; by dose (500 mg to 6g per day), frequency (once to thrice daily), delivery method (tablet, capsule, drink, powder), and duration (2 to 48 weeks). Patient inclusion was all-cause HF patients with ejection fraction (EF) <50% and no study was specific to DCM. While improvements in diastolic and systolic function, exercise capacity, and haemodynamic parameters were described, only EF and stroke volume were measured in enough studies to complete a meta-analysis; the association was not significant with all-cause HF (P<0.05). No significant safety concerns were reported. Conclusions: A formal clinical trial is needed to address whether taurine supplementation is beneficial to the approximately 1/250 individuals with DCM in the population.

Background: Taurine, 2-aminoethanesulfonic acid, is an amino acid found in animal products. Taurine is produced for human consumption as a supplement and ingredient in beverages. Supplementation is a safe, inexpensive, and effective treatment for dilated cardiomyopathy (DCM) in domestic mammals, however it is currently unlicensed in Europe and the United States for human medical treatment. Recent genome-wide association studies of DCM have identified the locus of the taurine transporter (SLC6A6). To assess whether taurine supplementation may be a novel therapeutic option for DCM, we undertook a systematic review. Methods: Four electronic databases (PubMed, Cochrane Central Register, Web of Science, Biomed Central) were searched until 11/03/21. Included studies of human participants reported measured phenotypes or symptoms for cardiomyopathy, heart failure (HF), or altered left ventricle structure or function, administering taurine in any formulation, by any method. Non-English articles were excluded. Meta-analysis was completed in R software (version 3.6.0). The Newcastle-Ottawa Scale quality assessment score (NOQAS) tool was used to assess bias. Results: 285 articles were identified, of which eleven met our criteria for inclusion. Only one paper was deemed “high quality” using the NOQAS tool. Taurine supplementation varied across studies; by dose (500 mg to 6g per day), frequency (once to thrice daily), delivery method (tablet, capsule, drink, powder), and duration (2 to 48 weeks). Patient inclusion was all-cause HF patients with ejection fraction (EF) <50% and no study was specific to DCM. While improvements in diastolic and systolic function, exercise capacity, and haemodynamic parameters were described, only EF and stroke volume were measured in enough studies to complete a meta-analysis; the association was not significant with all-cause HF (P<0.05). No significant safety concerns were reported. Conclusions: A formal clinical trial is needed to address whether taurine supplementation is beneficial to the approximately 1/250 individuals with DCM in the population.