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Association of vaginal bacterial communities and reproductive outcomes with prophylactic antibiotic exposure in a subfertile population undergoing in vitro fertilization: a prospective exploratory study.
Eskew, AM, Stout, MJ, Bedrick, BS, Riley, JK, Herter, BN, Gula, H, Jungheim, ES, Wylie, KM
F&S science. 2021;2(1):71-79
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Approximately 1 in 8 couples receive infertility services in their lifetime. However, despite the increasing usage of in vitro fertilisation (IVF) technologies, the success rate, as measured using live birth rates, is just <50% in women <35 years of age. A low-diversity, Lactobacillus-dominated microbiome in the female reproductive tract has been thought to be a sign of optimal reproductive health, whereas an increased microbial diversity has been shown to be associated with poorer reproductive outcomes. The aims of this study were to (a) explore the effect of prophylactic azithromycin treatment on the vaginal bacterial microbiome longitudinally throughout an IVF cycle and (b) determine whether the characteristics of the vaginal bacterial communities are associated with clinical outcomes. This study is an a priori prospective exploratory cohort study conducted as a part of an ongoing randomized, controlled noninferiority trial. Subjects in the parent trial were randomly assigned to an azithromycin group or no-azithromycin group. The female subjects of the parent trial who were aged between 18–43 years and undergoing the first IVF cycle with a fresh embryo transfer were eligible for this study (n=27). Results show that in vaginal microbiome samples taken at the time of egg retrieval and embryo transfer, changes in the taxonomic composition, alpha diversity, and beta diversity are not associated with azithromycin [antibiotic] exposure at the time of gonadotropin initiation. Furthermore, bacterial community structures at baseline are not predictive of those at the time of embryo transfer. Authors conclude that their findings highlight the importance of timing in the assessment of vaginal microbiome to determine its associations with reproductive outcomes.
Abstract
OBJECTIVE To determine whether prophylactic azithromycin is associated with the vaginal bacterial microbiome and clinical outcomes in subfertile women undergoing in vitro fertilization (IVF). DESIGN Prospective exploratory cohort study. SETTING Single academic fertility center. PATIENTS Subfertile women aged 18-43 years undergoing their first IVF cycle and fresh embryo transfer. INTERVENTION Primary exposure to prophylactic azithromycin (1 g orally) once at baseline. MAIN OUTCOME MEASURES The primary outcome was the effect of azithromycin on the vaginal microbiome compared with a no-azithromycin group at 3 time points throughout the IVF cycle (baseline, retrieval, and embryo transfer). The secondary outcomes were associations of vaginal bacterial communities with clinical outcomes. RESULTS A planned a priori exploratory cohort of 27 subjects (12 in the azithromycin treatment group and 15 in the no-azithromycin group) contributed 79 vaginal swabs for the analysis as part of an ongoing randomized, controlled noninferiority trial. No specific taxa were associated with azithromycin or pregnancy at any time point. Azithromycin did not affect alpha diversity or community stability. Although there were trends of a lower bacterial load and higher percentage of Lactobacillus species in the azithromycin group at the time of transfer, these were not statistically significant. In women who did not become pregnant, the percentage of Lactobacillus species was lower (P = .048; Hodges-Lehmann estimate of difference, 0.41; 95% confidence interval, 0.08-0.65) and the change in community composition over time was higher. The percentage of Lactobacillus species at baseline was not predictive of the percentage of Lactobacillus species at the time of embryo transfer. CONCLUSIONS Prophylactic azithromycin at baseline is not associated with changes in vaginal bacterial communities. Bacterial community features at the time of embryo transfer are associated with pregnancy. Bacterial community structures at baseline are not predictive of those at the time of embryo transfer. CLINICAL TRIAL REGISTRATION NUMBER NCT03386227.
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Human Gut Microbiota and Gastrointestinal Cancer.
Meng, C, Bai, C, Brown, TD, Hood, LE, Tian, Q
Genomics, proteomics & bioinformatics. 2018;16(1):33-49
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In this article the authors review research on the influence of the human gut microbiota on the development and progression of gastrointestinal cancers, and go into significant detail about the molecular mechanisms involved. Helicobacter pylori is a known risk factor for gastric cancer (GC) but other dysbiotic changes in the gut microbiota are also observed in GC. On the other hand, H. pylori is associated with a decreased risk for oesophageal cancer (OC). An increase in gram-negative bacteria is associated with OC, whilst gram-positive bacteria are dominant in a healthy oesophagus. Dietary factors are associated with the risk for colorectal cancer (CRC) and may be due to their effect on the bacterial composition of the bowel. The authors explore possible mechanisms for these links. Although the liver is considered sterile, carcinogenesis can be influenced by the gut microbiota through pathogens and bacterial metabolites which can disturb metabolic pathways and immune responses in the liver. In pancreatic cancer (PC), the gut microbiota may influence carcinogenesis by promoting inflammation. In addition to various lifestyle factors, H. pylori is a risk factor for PC. The authors also review the use of prebiotics, probiotics, synbiotics (a combination of pre- and pro-biotics) and Traditional Chinese Medicine as an adjunct to conventional cancer treatment to reduce side effects, as well as their potential preventive mechanisms.
Abstract
Human gut microbiota play an essential role in both healthy and diseased states of humans. In the past decade, the interactions between microorganisms and tumors have attracted much attention in the efforts to understand various features of the complex microbial communities, as well as the possible mechanisms through which the microbiota are involved in cancer prevention, carcinogenesis, and anti-cancer therapy. A large number of studies have indicated that microbial dysbiosis contributes to cancer susceptibility via multiple pathways. Further studies have suggested that the microbiota and their associated metabolites are not only closely related to carcinogenesis by inducing inflammation and immune dysregulation, which lead to genetic instability, but also interfere with the pharmacodynamics of anticancer agents. In this article, we mainly reviewed the influence of gut microbiota on cancers in the gastrointestinal (GI) tract (including esophageal, gastric, colorectal, liver, and pancreatic cancers) and the regulation of microbiota by diet, prebiotics, probiotics, synbiotics, antibiotics, or the Traditional Chinese Medicine. We also proposed some new strategies in the prevention and treatment of GI cancers that could be explored in the future. We hope that this review could provide a comprehensive overview of the studies on the interactions between the gut microbiota and GI cancers, which are likely to yield translational opportunities to reduce cancer morbidity and mortality by improving prevention, diagnosis, and treatment.
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Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity: A Comprehensive Review.
Mozaffarian, D
Circulation. 2016;133(2):187-225
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Diet-related cardiometabolic conditions, such as heart disease and diabetes, pose a significant health and economic burden across the world. In recent years, scientific advances and research have generated enormous insights, yet there remain many controversies and unanswered questions. This extensive review summarizes recent evidence of key-dietary components and their impact on cardiometabolic health. Amongst the topics covered are dietary patterns, food quality and processing, genetics, personalized nutrition, supplements, functional foods and the existing knowledge on selected food groups such as carbohydrates, meat and fats alongside relevant vitamins, minerals and plant compounds. The author highlights how an oversimplified concept of nutrition from previous decades, has led to an array of conflicting advice and undermined the nuanced and complex impact that diet and nutrition can have on the body. Thus in light of the evidence, food-based interventions and dietary patterns are suggested as favourable, with less focus on dietary components in isolation. Throughout the paper, the need for adjunct support to facilitate sustainable health-promoting behaviour changes is recognized. Calling for additional measures to address behaviour change, health systems reforms, targeting socioeconomic inequalities, employing novel technologies, and adequate policymaking. This overview of recent evidence yields a comprehensive source of information, worthwhile reviewing when designing personalised diet plans in support of cardiometabolic health.
Abstract
Suboptimal nutrition is a leading cause of poor health. Nutrition and policy science have advanced rapidly, creating confusion yet also providing powerful opportunities to reduce the adverse health and economic impacts of poor diets. This review considers the history, new evidence, controversies, and corresponding lessons for modern dietary and policy priorities for cardiovascular diseases, obesity, and diabetes mellitus. Major identified themes include the importance of evaluating the full diversity of diet-related risk pathways, not only blood lipids or obesity; focusing on foods and overall diet patterns, rather than single isolated nutrients; recognizing the complex influences of different foods on long-term weight regulation, rather than simply counting calories; and characterizing and implementing evidence-based strategies, including policy approaches, for lifestyle change. Evidence-informed dietary priorities include increased fruits, nonstarchy vegetables, nuts, legumes, fish, vegetable oils, yogurt, and minimally processed whole grains; and fewer red meats, processed (eg, sodium-preserved) meats, and foods rich in refined grains, starch, added sugars, salt, and trans fat. More investigation is needed on the cardiometabolic effects of phenolics, dairy fat, probiotics, fermentation, coffee, tea, cocoa, eggs, specific vegetable and tropical oils, vitamin D, individual fatty acids, and diet-microbiome interactions. Little evidence to date supports the cardiometabolic relevance of other popular priorities: eg, local, organic, grass-fed, farmed/wild, or non-genetically modified. Evidence-based personalized nutrition appears to depend more on nongenetic characteristics (eg, physical activity, abdominal adiposity, gender, socioeconomic status, culture) than genetic factors. Food choices must be strongly supported by clinical behavior change efforts, health systems reforms, novel technologies, and robust policy strategies targeting economic incentives, schools and workplaces, neighborhood environments, and the food system. Scientific advances provide crucial new insights on optimal targets and best practices to reduce the burdens of diet-related cardiometabolic diseases.