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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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Effect of Lactobacillus rhamnosus HN001 on carriage of Staphylococcus aureus: results of the impact of probiotics for reducing infections in veterans (IMPROVE) study.
Eggers, S, Barker, AK, Valentine, S, Hess, T, Duster, M, Safdar, N
BMC infectious diseases. 2018;18(1):129
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The bacteria Staphylococcus aureus (S. aureus) is found in the digestive tract, nostrils, mouth and armpits. Methicillin-resistant S. aureus (MRSA) is responsible for several difficult-to-treat infections in humans. Probiotics are emerging as an alternative to antibiotics in preventing or treating bacterial infections. This randomised controlled trial aimed to determine the ability of Lactobacillus rhamnosus (L. rhamnosus) HN001 to reduce S. aureus at several different body sites. Participants in the study were mostly male, with an average age of 64 years, and all carriers of S. aureus in one or more body sites. Participants were organised into groups depending on whether S. aureus was found within the gastrointestinal tract (GI) or in other body sites (extra-GI), and given either L. rhamnosus HN001 probiotic, or a placebo for four weeks. Subjects given the probiotic had 15% lower levels of S. aureus in their stool samples than those given the placebo at the end of the trial. They also had 73% reduced odds of methicillin-susceptible S. aureus (MSSA) presence, and 83% reduced odds of any S. aureus presence in the stool sample compared to the placebo group. No other sampling sites showed a significant difference in colonisation between the two groups. The authors concluded that use of daily oral L. rhamnosus HN001 reduced odds of carriage of S. aureus in the GI tract, however it did not eradicate S. aureus from other body sites. The results of the study support the use of this probiotic strain for reducing the population of S. aureus in the gut. Further studies are needed to assess the effectiveness of different probiotic strains and to compare probiotics with antibiotics in reducing S. aureus in other body sites.
Abstract
BACKGROUND Infection by Staphylococcus aureus (S. aureus) is a major cause of morbidity and mortality. Colonization by S. aureus increases the risk of infection. Little is known about decolonization strategies for S. aureus beyond antibiotics, however probiotics represent a promising alternative. A randomized controlled trial was conducted to determine the efficacy of Lactobacillus rhamnosus (L. rhamnosus) HN001 in reducing carriage of S. aureus at multiple body sites. METHODS One hundred thirteen subjects, positive for S. aureus carriage, were recruited from the William S. Middleton Memorial Medical Center, Madison, WI, USA, and randomized by initial site of colonization, either gastrointestinal (GI) or extra-GI, to 4-weeks of oral L. rhamnosus HN001 probiotic, or placebo. Nasal, oropharyngeal, and axillary/groin swabs were obtained, and serial blood and fecal samples were collected. Differences in prevalence of S. aureus carriage at the end of the 4-weeks of treatment were assessed. RESULTS The probiotic and placebo groups were similar in age, gender, and health history at baseline. S. aureus colonization within the stool samples of the extra-GI group was 15% lower in the probiotic than placebo group at the endpoint of the trial. Those in the probiotic group compared to the placebo group had 73% reduced odds (OR 0.27, 95% CI 0.07-0.98) of methicillin-susceptible S. aureus presence, and 83% reduced odds (OR 0.17, 95% CI 0.04-0.73) of any S. aureus presence in the stool sample at endpoint. CONCLUSION Use of daily oral L. rhamnosus HN001 reduced odds of carriage of S. aureus in the GI tract, however it did not eradicate S. aureus from other body sites. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01321606 . Registered March 21, 2011.
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Influence of diet on the gut microbiome and implications for human health.
Singh, RK, Chang, HW, Yan, D, Lee, KM, Ucmak, D, Wong, K, Abrouk, M, Farahnik, B, Nakamura, M, Zhu, TH, et al
Journal of translational medicine. 2017;15(1):73
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Gut microbiome plays an important role in modulating the risk of many chronic diseases through its impact on host immunity and metabolic health. Diet, in turn, can alter the composition of the microbiota. This paper reviewed current understanding of the effects of common dietary components and three select diets on gut microbiota composition and host health. Dietary components included plant and animal protein, saturated and unsaturated fats, digestible and non-digestible carbohydrates, probiotics and polyphenols. The diets included Western diet, gluten-free diet and Mediterranean diet. Based on the reviewed papers, the authors concluded that diet can modify the intestinal microbiome, which in turn has a profound impact on overall health. The impact can be beneficial or detrimental, depending on the abundance and identity of microbial populations and the nature of their interactions with the host. The authors also state that further research using large, long-term clinical trials to evaluate a greater variety of food components would be helpful in making specific dietary recommendations to patients.
Abstract
Recent studies have suggested that the intestinal microbiome plays an important role in modulating risk of several chronic diseases, including inflammatory bowel disease, obesity, type 2 diabetes, cardiovascular disease, and cancer. At the same time, it is now understood that diet plays a significant role in shaping the microbiome, with experiments showing that dietary alterations can induce large, temporary microbial shifts within 24 h. Given this association, there may be significant therapeutic utility in altering microbial composition through diet. This review systematically evaluates current data regarding the effects of several common dietary components on intestinal microbiota. We show that consumption of particular types of food produces predictable shifts in existing host bacterial genera. Furthermore, the identity of these bacteria affects host immune and metabolic parameters, with broad implications for human health. Familiarity with these associations will be of tremendous use to the practitioner as well as the patient.
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Reversal of cognitive decline: a novel therapeutic program.
Bredesen, DE
Aging. 2014;6(9):707-17
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Alzheimer’s Disease (AD) is estimated to affect 30 million individuals globally, with projections as high as 150 million by 2050 if no effective treatment is found. This report describes a personalised, multi-modal, therapeutic programme used with 10 individuals with various degrees of cognitive decline. The goal was to optimise metabolic parameters and lifestyle factors and was personalised based on laboratory test results. 9 out of 10 of the case study patients experienced improvement in cognitive abilities, beginning within 3-6 months of starting the programme. These effects were sustained at 2.5 year follow up. The 1 patient who did not benefit had advanced AD, in comparison to the other patients with subjective or mild cognitive decline. The authors call for a more extensive trial of the therapeutic programme.
Abstract
This report describes a novel, comprehensive, and personalized therapeutic program that is based on the underlying pathogenesis of Alzheimer's disease, and which involves multiple modalities designed to achieve metabolic enhancement for neurodegeneration (MEND). The first 10 patients who have utilized this program include patients with memory loss associated with Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI). Nine of the 10 displayed subjective or objective improvement in cognition beginning within 3-6 months, with the one failure being a patient with very late stage AD. Six of the patients had had to discontinue working or were struggling with their jobs at the time of presentation, and all were able to return to work or continue working with improved performance. Improvements have been sustained, and at this time the longest patient follow-up is two and one-half years from initial treatment, with sustained and marked improvement. These results suggest that a larger, more extensive trial of this therapeutic program is warranted. The results also suggest that, at least early in the course, cognitive decline may be driven in large part by metabolic processes. Furthermore, given the failure of monotherapeutics in AD to date, the results raise the possibility that such a therapeutic system may be useful as a platform on which drugs that would fail as monotherapeutics may succeed as key components of a therapeutic system.