Chemotherapy-Induced Intestinal Microbiota Dysbiosis Impairs Mucosal Homeostasis by Modulating Toll-like Receptor Signaling Pathways.

Chemotherapy-induced intestinal mucositis, a painful debilitating condition affecting up to 40-100% of patients undergoing chemotherapy, can reduce the patients' quality of life, add health care costs and even postpone cancer treatment. In recent years, the relationships between intestinal microbiota dysbiosis and mucositis have drawn much attention in mucositis research. Chemotherapy can shape intestinal microbiota, which, in turn, can aggravate the mucositis through toll-like receptor (TLR) signaling pathways, leading to an increased expression of inflammatory mediators and elevated epithelial cell apoptosis but decreased epithelial cell differentiation and mucosal regeneration. This review summarizes relevant studies related to the relationships of mucositis with chemotherapy regimens, microbiota, TLRs, inflammatory mediators, and intestinal homeostasis, aiming to explore how gut microbiota affects the pathogenesis of mucositis and provides potential new strategies for mucositis alleviation and treatment and development of new therapies.

Tying Small Changes to Large Outcomes: The Cautious Promise in Incorporating the Microbiome into Immunotherapy.

The role of the microbiome in immunology is a rapidly burgeoning topic of study. Given the increasing use of immune checkpoint inhibitor (ICI) therapy in cancers, along with the recognition that carcinogenesis has been linked to dysregulations of the immune system, much attention is now directed at potentiation of ICI efficacy, as well as minimizing the incidence of treatment-associated immune-related adverse events (irAEs). We provide an overview of the major research establishing links between the microbiome to tumorigenesis, chemotherapy and radiation potentiation, and ICI efficacy and irAE development.

Pediatric fever in neutropenia with bacteremia-Pathogen distribution and in vitro antibiotic susceptibility patterns over time in a retrospective single-center cohort study.

BACKGROUND: Fever in neutropenia (FN) is a potentially life-threatening complication of chemotherapy in pediatric cancer patients. The current standard of care at most institutions is emergency hospitalization and empirical initiation of broad-spectrum antibiotic therapy. METHODS: We analyzed in retrospect FN episodes with bacteremia in pediatric cancer patients in a single center cohort from 1993 to 2012. We assessed the distribution of pathogens, the in vitro antibiotic susceptibility patterns, and their trends over time. RESULTS: From a total of 703 FN episodes reported, we assessed 134 FN episodes with bacteremia with 195 pathogens isolated in 102 patients. Gram-positive pathogens (124, 64%) were more common than Gram-negative (71, 36%). This proportion did not change over time (p = 0.26). Coagulase-negative staphylococci (64, 32%), viridans group streptococci (42, 22%), Escherichia coli (33, 17%), Klebsiella spp. (10, 5%) and Pseudomonas aeruginosa (nine, 5%) were the most common pathogens. Comparing the in vitro antibiotic susceptibility patterns, the antimicrobial activity of ceftriaxone plus amikacin (64%; 95%CI: 56%-72%), cefepime (64%; 95%CI 56%-72%), meropenem (64%; 95%CI 56%-72), and piperacillin/tazobactam (62%; 95%CI 54%-70%), respectively, did not differ significantly. The addition of vancomycin to those regimens would have increased significantly in vitro activity to 99% for ceftriaxone plus amikacin, cefepime, meropenem, and 96% for piperacillin/tazobactam (p < 0.001). CONCLUSIONS: Over two decades, we detected a relative stable pathogen distribution and found no relevant trend in the antibiotic susceptibility patterns. Different recommended antibiotic regimens showed comparable in vitro antimicrobial activity.

Gut microbiota as a target to limit toxic effects of traditional Chinese medicine: Implications for therapy.

Traditional Chinese medicines (TCMs) are medicines that are widely used in oriental countries under the guidance of ancient Chinese medicinal philosophies. With thousands of years of experiences in fighting against diseases, TCMs are gaining increasing importance in the world. Although the efficacy of TCMs is well recognized in clinic, the toxicity of TCMs has become a serious issue around the world in recent years. In general, the toxicity of TCMs is caused by the toxic medicinal compounds and contaminants in TCMs such as pesticides, herbicides, and heavy metals. Recent studies have demonstrated that gut microbiota can interact with TCMs and thus influence the toxicity of TCMs. However, there is no focused review on gut microbiota and the toxicity of TCMs. Here, we summarized the influences of the gut microbiota on the toxicity of medicinal compounds in TCMs and the corresponding mechanisms were offered. Then, we discussed the relationships between gut microbiota and the TCM contaminants. In addition, we discussed the methods of manipulating gut microbiota to reduce the toxicity of TCMs. At the end of this review, the perspectives on gut microbiota and the toxicity of TCMs were also discussed.

Intestinal Microbiome Associated With Immune-Related Adverse Events for Patients Treated With Anti-PD-1 Inhibitors, a Real-World Study.

Aim: Immune checkpoint inhibitors (ICIs) have updated the treatment landscape for patients with advanced malignancies, while their clinical prospect was hindered by severe immune-related adverse events (irAEs). The aim of this study was to research the association between gut microbiome diversity and the occurrence of ICI-induced irAEs. Patients and Method: We prospectively obtained the baseline fecal samples and clinical data from patients treated with anti-PD-1 inhibitors as monotherapy or in combination with chemotherapy or antiangiogenesis regardless of treatment lines. The 16S rRNA V3-V4 sequencing was used to test the gene amplicons of fecal samples. The development of irAEs was evaluated and monitored from the beginning of therapy based on CTCAE V5.01. Results: A total of 150 patients were included in the study and followed up for at least 6 months. A total of 90 (60%) patients developed at least one type of adverse effect, among which mild irAEs (grades 1-2) occurred in 65 patients (72.22%) and severe irAEs (grades 3-5) in 25 patients (27.78%). Patients with severe irAEs showed a visible higher abundance of Streptococcus, Paecalibacterium, and Stenotrophomonas, and patients with mild irAEs had a higher abundance of Faecalibacterium and unidentified_Lachnospiraceae. With the aid of a classification model constructed with 5 microbial biomarkers, patients without irAEs were successfully distinguished from those with severe irAEs (AUC value was 0.66). Conclusion: Certain intestinal bacteria can effectively distinguish patients without irAEs from patients with severe irAEs and provide evidence of gut microbiota as an informative source for developing predictive biomarkers to predict the occurrence of irAEs.

Factors influencing the length of hospital stay during the intensive phase of multidrug-resistant tuberculosis treatment at Amhara regional state hospitals, Ethiopia: a retrospective follow up study.

BACKGROUND: The length of hospital stay is the duration of hospitalization, which reflects disease severity and resource utilization indirectly. Generally, tuberculosis is considered an ambulatory disease that could be treated at DOTs clinics; however, admission remains an essential component for patients' clinical stabilization. Hence, this study aimed to identify factors influencing hospital stay length during the intensive phase of multidrug-resistant tuberculosis treatment. METHODS: A retrospective follow-up study was conducted at three hospitals, namely the University of Gondar comprehensive specialized, Borumeda, and Debremarkos referral hospitals from September 2010 to December 2016 (n = 432). Data extracted from hospital admission/discharge logbooks and individual patient medical charts. A binary logistic regression analysis was used to identify factors associated with more extended hospital stays during the intensive phase of multidrug-resistant tuberculosis treatment. RESULT: Most patients (93.5%) had a pulmonary form of multidrug-resistant tuberculosis and 26.2% had /TB/HIV co-infections. The median length of hospital stays was 62 (interquartile range from 36 to 100) days. The pulmonary form of tuberculosis (Adjusted odds ratio [AOR], 3.47, 95% confidence interval [CI]; 1.31 to 9.16), bedridden functional status (AOR = 2.88, 95%CI; 1.29 to 6.43), and adverse drug effects (AOR = 2.11, 95%CI; 1.35 to 3.30) were factors associated with extended hospital stays. CONCLUSION: This study revealed that the length of hospital-stay differed significantly between the hospitals. The pulmonary form of tuberculosis decreased functional status at admission and reported adverse drug reactions were determinants of more extended hospital stays. These underscore the importance of early case detection and prompt treatment of adverse drug effects.

Microbiota-Gut-Brain Axis: New Therapeutic Opportunities.

The traditional fields of pharmacology and toxicology are beginning to consider the substantial impact our gut microbiota has on host physiology. The microbiota-gut-brain axis is emerging as a particular area of interest and a potential new therapeutic target for effective treatment of central nervous system disorders, in addition to being a potential cause of drug side effects. Microbiota-gut-brain axis signaling can occur via several pathways, including via the immune system, recruitment of host neurochemical signaling, direct enteric nervous system routes and the vagus nerve, and the production of bacterial metabolites. Altered gut microbial profiles have been described in several psychiatric and neurological disorders. Psychobiotics, live biotherapeutics or substances whose beneficial effects on the brain are bacterially mediated, are currently being investigated as direct and/or adjunctive therapies for psychiatric and neurodevelopmental disorders and possibly for neurodegenerative disease, and they may emerge as new therapeutic options in the clinical management of brain disorders.

The Role of the Microbiome in Drug Response.

The microbiome is known to regulate many aspects of host health and disease and is increasingly being recognized as a key mediator of drug action. However, investigating the complex multidirectional relationships between drugs, the microbiota, and the host is a challenging endeavor, and the biological mechanisms that underpin these interactions are often not well understood. In this review, we outline the current evidence that supports a role for the microbiota as a contributor to both the therapeutic benefits and side effects of drugs, with a particular focus on those used to treat mental disorders, type 2 diabetes, and cancer. We also provide a snapshot of the experimental and computational tools that are currently available for the dissection of drug-microbiota-host interactions. The advancement of knowledge in this area may ultimately pave the way for the development of novel microbiota-based strategies that can be used to improve treatment outcomes.

Discovering the Microbial Enzymes Driving Drug Toxicity with Activity-Based Protein Profiling.

It is increasingly clear that interindividual variability in human gut microbial composition contributes to differential drug responses. For example, gastrointestinal (GI) toxicity is not observed in all patients treated with the anticancer drug irinotecan, and it has been suggested that this variability is a result of differences in the types and levels of gut bacterial ß-glucuronidases (GUSs). GUS enzymes promote drug toxicity by hydrolyzing the inactive drug-glucuronide conjugate back to the active drug, which damages the GI epithelium. Proteomics-based identification of the exact GUS enzymes responsible for drug reactivation from the complexity of the human microbiota has not been accomplished, however. Here, we discover the specific bacterial GUS enzymes that generate SN-38, the active and toxic metabolite of irinotecan, from human fecal samples using a unique activity-based protein profiling (ABPP) platform. We identify and quantify gut bacterial GUS enzymes from human feces with an ABPP-enabled proteomics pipeline and then integrate this information with ex vivo kinetics to pinpoint the specific GUS enzymes responsible for SN-38 reactivation. Furthermore, the same approach also reveals the molecular basis for differential gut bacterial GUS inhibition observed between human fecal samples. Taken together, this work provides an unprecedented technical and bioinformatics pipeline to discover the microbial enzymes responsible for specific reactions from the complexity of human feces. Identifying such microbial enzymes may lead to precision biomarkers and novel drug targets to advance the promise of personalized medicine.

Gut microbiota: what is its place in pharmacology?

Introduction: In each section of the human gastrointestinal (GI) tract we may find bacteria that are adapted to local conditions and fulfill an important role in the proper functioning of the body. The gut microorganisms are crucial in human physiology in areas as diverse as the brain and the immune system functions. Therefore, there is a close relationship between the intestinal microbiota, its metabolic activity, and health of the host. Areas covered: In this review, we explore the host-microbiome interactions and characterize the role they may play in drug metabolism and toxicity. The study is based on pertinent papers that were retrieved by a selective search using relevant keywords in PubMed and ScienceDirect databases. Expert opinion: Increasing unhealthy eating habits, stress, antibiotic therapy, unfavorable environmental factors, and genetic predisposition contribute to imbalances in the composition and function of the GI tract microbes and the initiation and progression of disease processes. Restoration of the balanced gut microbiota composition is possible by oral administration of probiotics.

Chemotherapy-induced oral mucositis is associated with detrimental bacterial dysbiosis.

BACKGROUND: Gastrointestinal mucosal injury (mucositis), commonly affecting the oral cavity, is a clinically significant yet incompletely understood complication of cancer chemotherapy. Although antineoplastic cytotoxicity constitutes the primary injury trigger, the interaction of oral microbial commensals with mucosal tissues could modify the response. It is not clear, however, whether chemotherapy and its associated treatments affect oral microbial communities disrupting the homeostatic balance between resident microorganisms and the adjacent mucosa and if such alterations are associated with mucositis. To gain knowledge on the pathophysiology of oral mucositis, 49 subjects receiving 5-fluorouracil (5-FU) or doxorubicin-based chemotherapy were evaluated longitudinally during one cycle, assessing clinical outcomes, bacterial and fungal oral microbiome changes, and epithelial transcriptome responses. As a control for microbiome stability, 30 non-cancer subjects were longitudinally assessed. Through complementary in vitro assays, we also evaluated the antibacterial potential of 5-FU on oral microorganisms and the interaction of commensals with oral epithelial tissues. RESULTS: Oral mucositis severity was associated with 5-FU, increased salivary flow, and higher oral granulocyte counts. The oral bacteriome was disrupted during chemotherapy and while antibiotic and acid inhibitor intake contributed to these changes, bacteriome disruptions were also correlated with antineoplastics and independently and strongly associated with oral mucositis severity. Mucositis-associated bacteriome shifts included depletion of common health-associated commensals from the genera Streptococcus, Actinomyces, Gemella, Granulicatella, and Veillonella and enrichment of Gram-negative bacteria such as Fusobacterium nucleatum and Prevotella oris. Shifts could not be explained by a direct antibacterial effect of 5-FU, but rather resembled the inflammation-associated dysbiotic shifts seen in other oral conditions. Epithelial transcriptional responses during chemotherapy included upregulation of genes involved in innate immunity and apoptosis. Using a multilayer epithelial construct, we show mucositis-associated dysbiotic shifts may contribute to aggravate mucosal damage since the mucositis-depleted Streptococcus salivarius was tolerated as a commensal, while the mucositis-enriched F. nucleatum displayed pro-inflammatory and pro-apoptotic capacity. CONCLUSIONS: Altogether, our work reveals that chemotherapy-induced oral mucositis is associated with bacterial dysbiosis and demonstrates the potential for dysbiotic shifts to aggravate antineoplastic-induced epithelial injury. These findings suggest that control of oral bacterial dysbiosis could represent a novel preventive approach to ameliorate oral mucositis.

Detection of vaginal lactobacilli as probiotic candidates.

The vaginal microbiota of healthy women is dominated by lactobacilli, which exerts important health-promoting effects to the host. In the present study, 261 lactobacilli isolated from vagina of healthy women were screened for their potential probiotic characteristics. Safety features (haemolytic activity, antibiotic susceptibility, bile salt hydrolase activity) and functional properties (resistance to low pH and bile salts, lysozyme tolerance, gastrointestinal survival, antagonistic activity against pathogens, hydrophobicity, auto-aggregation, and co-aggregation abilities, hydrogen peroxide production, biofilm formation, exopolysaccharide production, adhesion capacity to both normal human vagina epithelial cells and Caco-2 epithelial cells, and lactic acid production) were in depth evaluated. Seven strains, identified as Lactobacillus rhamnosus, Lactobacillus helveticus and Lactobacillus salivarius fulfilled the criteria described above. Therefore, the vaginal ecosystem represents a suitable source of probiotic candidates that could be used in new functional formulates for both gastrointestinal and vaginal eubiosis.

Potential of Omega-3 Polyunsaturated Fatty Acids in Managing Chemotherapy- or Radiotherapy-Related Intestinal Microbial Dysbiosis.

Chemotherapy- or radiotherapy-related intestinal microbial dysbiosis is one of the main causes of intestinal mucositis. Cases of bacterial translocation into peripheral blood and subsequent sepsis occur as a result of dysfunction in the intestinal barrier. Evidence from recent studies depicts the characteristics of chemotherapy- or radiotherapy-related intestinal microbial dysbiosis, which creates an imbalance between beneficial and harmful bacteria in the gut. Decreases in beneficial bacteria can lead to a weakening of the resistance of the gut to harmful bacteria, resulting in robust activation of proinflammatory signaling pathways. For example, lipopolysaccharide (LPS)-producing bacteria activate the nuclear transcription factor-κB signaling pathway through binding with Toll-like receptor 4 on stressed epithelial cells, subsequently leading to secretion of proinflammatory cytokines. Nevertheless, various studies have found that the omega-3 (n-3) polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid and eicosapentaenoic acid can reverse intestinal microbial dysbiosis by increasing beneficial bacteria species, including Lactobacillus, Bifidobacterium, and butyrate-producing bacteria, such as Roseburia and Coprococcus. In addition, the n-3 PUFAs decrease the proportions of LPS-producing and mucolytic bacteria in the gut, and they can reduce inflammation as well as oxidative stress. Importantly, the n-3 PUFAs also exert anticancer effects in colorectal cancers. In this review, we summarize the characteristics of chemotherapy- or radiotherapy-related intestinal microbial dysbiosis and introduce the contributions of dysbiosis to the pathogenesis of intestinal mucositis. Next, we discuss how n-3 PUFAs could alleviate chemotherapy- or radiotherapy-related intestinal microbial dysbiosis. This review provides new insights into the clinical administration of n-3 PUFAs for the management of chemotherapy- or radiotherapy-related intestinal microbial dysbiosis.

Adverse events of high-dose tigecycline in the treatment of ventilator-associated pneumonia due to multidrug-resistant pathogens.

The off-label uses of tigecycline (TGC) to treat ventilator-associated pneumonia (VAP) have aroused worldwide concerns. The efficacy about TGC has been recently reported. However, the adverse events (AEs) remain controversial. Our study aims to analyze the safety of the high-dose (HD) regimens in the treatment of VAP due to multidrug-resistant (MDR) pathogens.The clinical data of 134 patients who were diagnosed with VAP from January 2013 to December 2015 in the NeuroScience Care Unit (NCU) were analyzed retrospectively. The incidence and the occurrence time of AEs, 28-day mortality, and the factors of clinical effectiveness were explored.A total of 54 patients received the standard dose group (SD), 69 in the HD, and 11 in the nonstandard HD group (NHD). Acinetobacter baumannii were the main pathogenic bacteria. There was no statistic difference in the incidence of AEs and the 28-day mortality among the 3 groups (P > .05). Total bilirubin (TBIL) increased significantly after SD of TGC treatment (P = .004). Liver dysfunction occurred the latest (10.83 ±â€Š7.08), not in the duration of HD group (9.63 ±â€Š3.92), whereas in the SD group (13.00 ±â€Š7.57) and NHD group (12.64 ±â€Š3.70). Patients with septic shock, MODS, and higher APACHE II score were of high risk in mortality. The HD group was associated with higher clinical effective rate and bacteria clearance rate.HD TGC was relatively safe and tolerable in ICU patients. The risk of side effects was related to the TGC duration, although not increased as the dosage rose. Full course of the HD regimen was associated with better outcomes for the treatment of VAP patients, especially for the MDR gram-negative bacilli infection. Inappropriate antimicrobial treatment might lead to clinical treatment failure.

Gut microbiota in toxicological risk assessment of drugs and chemicals: The need of hour.

The advent of industrial revolution caused a large inflow of synthetic chemicals for medical, agricultural, industrial and other purposes in the world. In general, these chemicals were subjected to toxicological risk assessment for human health and ecology before release for public use. But today we are witnessing a negative impact of some of these chemicals on human health and environment indicating an underestimation of toxic effects by current risk assessment protocol. Recent studies established gut microbiota as one of the key player in intercession of toxicity of drugs and synthetic chemicals. Hence, the need of the hour is to include the assessment for microbiota specifically gut microbiota in human toxicological risk assessment protocol. Herewith we are proposing a framework for assessment of gut microbiota upon exposure to drugs or chemicals.

Systematic review: human gut dysbiosis induced by non-antibiotic prescription medications.

BACKGROUND: Global prescription drug use has been increasing continuously for decades. The gut microbiome, a key contributor to health status, can be altered by prescription drug use, as antibiotics have been repeatedly described to have both short-term and long-standing effects on the intestinal microbiome. AIM: To summarise current findings on non-antibiotic prescription-induced gut microbiome changes, focusing on the most frequently prescribed therapeutic drug categories. METHODS: We conducted a systematic review by first searching in online databases for indexed articles and abstracts in accordance with PRISMA guidelines. Studies assessing the intestinal microbiome alterations associated with proton pump inhibitors (PPIs), metformin, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, statins and antipsychotics were included. We only included studies using culture-independent molecular techniques. RESULTS: Proton pump inhibitors and antipsychotic medications are associated with a decrease in α diversity in the gut microbiome, whereas opioids were associated with an increase in α diversity. Metformin and NSAIDs were not associated with significant changes in α diversity. ß diversity was found to be significantly altered with all drugs, except for NSAIDs. PPI use was linked to a decrease in Clotridiales and increase in Actinomycetales, Micrococcaceae and Streptococcaceae, which are changes previously implicated in dysbiosis and increased susceptibility to Clostridium difficile infection. Consistent results showed that PPIs, metformin, NSAIDs, opioids and antipsychotics were either associated with increases in members of class Gammaproteobacteria (including Enterobacter, Escherichia, Klebsiella and Citrobacter), or members of family Enterococcaceae, which are often pathogens isolated from bloodstream infections in critically ill patients. We also found that antipsychotic treatment, usually associated with an increase in body mass index, was marked by a decreased ratio of Bacteroidetes:Firmicutes in the gut microbiome, resembling trends seen in obese patients. CONCLUSIONS: Non-antibiotic prescription drugs have a notable impact on the overall architecture of the intestinal microbiome. Further explorations should seek to define biomarkers of dysbiosis induced by specific drugs, and potentially tailor live biotherapeutics to counter this drug-induced dysbiosis. Many other frequently prescribed drugs should also be investigated to better understand the link between these drugs, the microbiome and health status.

Depletion of enteric bacteria diminishes leukocyte infiltration following doxorubicin-induced small intestinal damage in mice.

BACKGROUND & AIMS: While enteric bacteria have been shown to play a critical role in other forms of intestinal damage, their role in mediating the response to the chemotherapeutic drug Doxorubicin (Doxo) is unclear. In this study, we used a mouse model of intestinal bacterial depletion to evaluate the role enteric bacteria play in mediating Doxo-induced small intestinal damage and, more specifically, in mediating chemokine expression and leukocyte infiltration following Doxo treatment. An understanding of this pathway may allow for development of intervention strategies to reduce chemotherapy-induced small intestinal damage. METHODS: Mice were treated with (Abx) or without (NoAbx) oral antibiotics in drinking water for four weeks and then with Doxo. Jejunal tissues were collected at various time points following Doxo treatment and stained and analyzed for apoptosis, crypt damage and restitution, and macrophage and neutrophil number. In addition, RNA expression of inflammatory markers (TNFα, IL1-ß, IL-10) and cytokines (CCL2, CC7, KC) was assessed by qRT-PCR. RESULTS: In NoAbx mice Doxo-induced damage was associated with rapid induction of apoptosis in jejunal crypt epithelium and an increase weight loss and crypt loss. In addition, we observed an increase in immune-modulating chemokines CCL2, CCL7 and KC and infiltration of macrophages and neutrophils. In contrast, while still positive for induction of apoptosis following Doxo treatment, Abx mice showed neither the overall weight loss nor crypt loss seen in NoAbx mice nor the increased chemokine expression and leukocyte infiltration. CONCLUSION: Enteric bacteria play a critical role in Doxo-induced small intestinal damage and are associated with an increase in immune-modulating chemokines and cells. Manipulation of enteric bacteria or the damage pathway may allow for prevention or treatment of chemotherapy-induced small intestinal damage.

The influence of gut microbiota on drug metabolism and toxicity.

INTRODUCTION: Gut microbiota plays critical roles in drug metabolism. The variation of gut microbiota contributes to the interindividual differences toward drug therapy including drug-induced toxicity and efficacy. Accordingly, the investigation and elucidation of gut microbial impacts on drug metabolism and toxicity will not only facilitate the way of personalized medicine, but also improve rational drug design. AREAS COVERED: This review provides an overview of the microbiota-host co-metabolism on drug metabolism and summarizes 30 clinical drugs that are co-metabolized by host and gut microbiota. Moreover, this review is specifically focused on elucidating the gut microbial modulation of some clinical drugs, in which the gut microbial influences on drug metabolism, drug-induced toxicity and efficacy are discussed. EXPERT OPINION: The gut microbial contribution to drug metabolism and toxicity is increasingly recognized, but remains largely unexplored due to the extremely complex relationship between gut microbiota and host. The mechanistic elucidation of gut microbiota in drug metabolism is critical before any practical progress in drug design or personalized medicine could be made by modulating human gut microbiota. Analytical technique innovation is urgently required to strengthen our capability in recognizing microbial functions, including metagenomics, metabolomics and the integration of multidisciplinary knowledge.

Cometabolism of microbes and host: implications for drug metabolism and drug-induced toxicity.

The recognition of the gut microbial-mammalian metabolic axis and its implications in human metabolic disease opens a new window to understanding the contribution of the gut microbiome to drug metabolism and drug-induced toxicity. The integrative omics approaches, including pharmacometabonomics and metagenomics, have demonstrated great promise for characterizing xenobiotic interventions that are associated with wide variation in efficacy or toxicity in humans, as well as for predicting individual response and susceptibility to toxicity.