Introduction: Scientific interest in the gut microbiota is increasing due to improved understanding of its implications in human health and disease. In patients with kidney disease, gut microbiota-derived uremic toxins directly contribute to altered nonrenal drug clearance. Microbial imbalances, known as dysbiosis, potentially increase formation of microbiota-derived toxins, and diminished renal clearance leads to toxin accumulation. High concentrations of microbiota-derived toxins such as indoxyl sulfate and p-cresol sulfate perpetrate interactions with drug metabolizing enzymes and transporters, which provides a mechanistic link between increases in drug-related adverse events and dysbiosis in kidney disease.
Areas covered: This review summarizes the effects of microbiota-derived uremic toxins on hepatic phase I and phase II drug metabolizing enzymes and drug transporters. Research articles that tested individual toxins were included. Therapeutic strategies to target microbial toxins are also discussed.
Expert commentary: Large interindividual variability in toxin concentrations may explain some differences in nonrenal clearance of medications. Advances in human microbiome research provide unique opportunities to systematically evaluate the impact of individual and combined microbial toxins on drug metabolism and transport, and to explore microbiota-derived uremic toxins as potential therapeutic targets. 相似文献
Functional foods have nutritional properties and organic functions, which are beneficial to health. Certain types of functional food components are so‐called phytoestrogens, non‐steroidal compounds derived from the metabolism of precursors contained in plants, which originate secondary metabotypes known to induce biological responses and by mimicry or modulating the action of endogenous estrogen. These molecules are involved in several physiological and pathological processes related to reproduction, bone remodeling, skin, cardiovascular, nervous, immune systems, and metabolism. This review aimed to present an overview of phytoestrogens regarding their chemical structure, actions, and effects in the organism given several pathologies. Several studies have demonstrated beneficial phytoestrogen actions, such as lipid profile improvement, cognitive function, menopause, oxidative stress, among others. Phytoestrogens effects are not completely elucidated, being necessary future research to understand the exact action mechanisms, whether they are via estrogen receptor or whether other hidden mechanisms produce these effects. Thus, this review makes a general approach to the phytoestrogen actions, beneficial effects, risk and limitations. However, the complexities of biological effects after ingestion of phytoestrogens and the differences in their metabolism and bioavailability indicate that interpretation of either risk or benefits needs to be made with caution. 相似文献
BackgroundFew studies have assessed differences in the gut microbiota composition after bariatric surgery in the long term or whether differences are correlated with remission of type 2 diabetes.ObjectivesThis observational study assessed differences in the gut microbiota between individuals at up to 13 years after surgery and a comparison group of individuals with severe obesity. The relationship between type 2 diabetes remission and the gut microbiota was also assessed.SettingUniversity.MethodsStool samples were collected from individuals completing bariatric surgery (surgery group; n = 16) and individuals with severe obesity that did not receive surgery (nonsurgery group; n = 19) as part of the 12-year follow-up in the Utah Obesity Study. Metabolic health data were collected at baseline and the follow-up examination. The gut microbiota was quantified by sequencing the V4 region of the 16 S rRNA gene. Significant differences in microbiota composition with surgery and other covariates were determined by Unifrac distance analysis and permutational multivariate analysis of variance. Significant differences in the relative abundance of individual bacterial taxa were assessed using analysis of composition of microbiomes software.ResultsThe surgery group had higher relative abundances of Verrucomicrobiaceae (5.7 ± 1.3% versus 1.1 ± .3%) and Streptococcaceae (6.3 ± 1.0% versus 3.2 ± .8%), but lower relative abundances of Bacteroidaceae (8.8 ± 1.8% versus 18.6 ± 2.3%) 10.6 years after surgery. In a small subset of 8 individuals, a higher relative abundance of Akkermansia muciniphila was correlated with type 2 diabetes remission.ConclusionsDifferences in the gut microbiota are evident a decade after bariatric surgery compared with individuals with severe obesity that did not undergo surgery. The observed long-term differences are consistent with previous findings. 相似文献
Primary sclerosing cholangitis (PSC) is a common indication for liver transplantation (LT). Up to 25% of patients experience recurrence of PSC (rPSC) after LT, which is associated with significant morbidity and mortality. To date, it is not possible to predict which patients are at risk for rPSC. The aetiology of PSC is complex and is speculated to involve translocation of intestinal bacteria to the liver, because of its frequent co-occurrence with inflammatory bowel diseases (IBD). Here, we investigate whether the mucosal intestinal microbiome of PSC patients (n = 97) at time of first LT can identify those patients who will develop rPSC. 16S gene sequencing of bacterial DNA isolated from formalin-fixed paraffin-embedded biopsies showed that PSC patients with Crohn’s disease (n = 15) have a reduced microbial diversity and that inflammation of the mucosa is associated with beta-diversity changes and feature differences. No differences in alpha- or beta diversity were observed between patients with rPSC (n = 14) and without rPSC (n = 83). However, many over-represented bacterial features were detected in patients with rPSC, while surprisingly, those without recurrence of disease were characterized by an increased presence of the Gammaproteobacteria Shigella. This pilot study warrants further investigation into bacterial differences between rPSC and non-rPSC patients. 相似文献
BackgroundRoux-en Y gastric bypass (RYGB) and ileal transposition (IT) surgeries produce weight loss and improve diabetic control; however, the mechanisms of glycemic improvements are largely unknown. Because skeletal muscle and liver play a key role in glucose homeostasis, we compared the effects of RYGB and IT surgeries on key molecules of glucose and lipid metabolism in muscle and liver.MethodsSprague-Dawley rats were subjected to RYGB, IT, or sham surgeries; sham-animals were ad-lib fed or pair-fed to RYGB rats (n = 7-9/group). At 8 weeks postoperatively, blood samples were collected for glucagon-like peptide-1 (GLP-1) and insulin analyses by ELISA. Leg muscle and liver tissues were analyzed for mRNA (RT-qPCR) and/or protein abundance (immuno blotting) of important molecules of glucose and lipid metabolism [glucose transporter-4 (GLUT-4), hexokinase, phosphofructokinase (PFK), adenosine monophosphate activated protein kinase-α (AMPKα), cytochrome C oxidase-IV (COX-IV), citrate synthase, carnitine palmitoyl transferase-1 (CPT-1), medium-chain acyl-CoA dehydrogenase (MCAD), peroxisome proliferator-activated receptor gamma co-activator 1 α (PGC-1 α), PGC-1-related coactivator (PRC), uncoupling protein-3 (UCP-3)].ResultsPlasma GLP-1 concentrations were increased comparably with RYGB and IT. RYGB and IT increased muscle GLUT-4 protein content, muscle hexokinase mRNA, and liver PFK mRNA. IT increased muscle AMPKα and COX-IV protein content and liver citrate synthase activity. IT increased muscle CPT-1, MCAD and PRC mRNA, whereas RYGB increased UCP-3 mRNA in muscle and liver, and PGC-1 α mRNA in liver.ConclusionThe data suggest that RYGB and IT surgeries lead to enhanced GLP-1 secretion and produce similar stimulatory effects on important molecules of glucose metabolism but differential effects on key molecules of lipid oxidation in muscle and liver. 相似文献
Increasing antibiotic resistance in bacteria that cause zoonotic infections is a major problem for farmers rearing animals for food as well as for consumers who eat the contaminated meat resulting in food-borne infections. Bacteriophages incorporated in animal feed may help reduce carriage and infections in animals including chickens and pigs. There are, however, unmet challenges in protecting phages from processing stresses e.g., during animal feed pelleting operations and during transit of phages through the acidic gastric environment. Core-shell capsules were produced using a concentric nozzle and commercially available encapsulation equipment to fabricate capsules with phages formulated in an oil-in-water microemulsion in the core. pH-responsive capsules released the encapsulated phage cargo within 10–30 min triggered by changes in local environmental pH typically found in the lower gastrointestinal (GI) tract of animals. Acid stability of phages exposed to pH values as low as pH 1 was demonstrated. Encapsulated phages were able to withstand exposure to 95 °C wet heat thermal stress for up to 120 s, conditions typically encountered during feed pellet extrusion processing. Free phages were inactivated within 15 s under these conditions. The present study demonstrates that encapsulation of bacteriophages in core-shell pH-responsive capsules with water-in-oil emulsified phages in the core significantly improves phage viability upon exposure to processing and environmental stresses that require consideration during production of animal feed and application in animals for biocontrol. The results from this study should help guide future development of phage formulations suitable for use in animal feed for animal biocontrol applications. 相似文献