The intersection of social determinants of health, the microbiome, and health outcomes in immigrants: A scoping review.

In the present scoping review, we explore whether existing evidence supports the premise that social determinants of health (SDoH) affect immigrant health outcomes through their effects on the microbiome. We adapt the National Institute on Minority Health and Health Disparities' research framework to propose a conceptual model that considers the intersection of SDoH, the microbiome, and health outcomes in immigrants. We use this conceptual model as a lens through which to explore recent research about SDoH, biological factors associated with changes to immigrants' microbiomes, and long-term health outcomes. In the 17 articles reviewed, dietary acculturation, physical activity, ethnicity, birthplace, age at migration and length of time in the host country, socioeconomic status, and social/linguistic acculturation were important determinants of postmigration microbiome-related transformations. These factors are associated with progressive shifts in microbiome profile with time in host country, increasing the risks for cardiometabolic, mental, immune, and inflammatory disorders and antibiotic resistance. The evidence thus supports the premise that SDoH influence immigrants' health postmigration, at least in part, through their effects on the microbiome. Omission of important postmigration social-ecological variables (e.g., stress, racism, social/family relationships, and environment), limited research among minoritized subgroups of immigrants, complexity and inter- and intra-individual differences in the microbiome, and limited interdisciplinary and biosocial collaboration restrict our understanding of this area of study. To identify potential microbiome-based interventions and promote immigrants' well-being, more research is necessary to understand the intersections of immigrant health with factors from the biological, behavioral/psychosocial, physical/built environment, and sociocultural environment domains at all social-ecological levels.

Gut microbiota composition and diversity before, during, and two months after rifamycin-based tuberculosis preventive therapy.

Tuberculosis (TB) preventive therapy (TPT) is an effective strategy to eliminate TB in low-incidence settings. Shorter TPT regimens incorporating the antimicrobial class of rifamycins are designed to improve adherence and completion rates but carry the risk of modifications to the gut microbiota. We enrolled six subjects diagnosed with latent TB infection (LTBI) who accepted to initiate TPT. We also enrolled six healthy volunteers unexposed to the rifamycins. We profiled the gut microbiota using 16S rRNA amplicon sequencing (V1-V2 region) to document the immediate effect of rifamycin-based TPT on the gut microbiota composition and tracked recovery to baseline two months after TPT. Overall, TPT accounted for 17% of the variance in gut microbial community dissimilarity. This rifamycin-based TPT induced dysbiosis was characterized by a depletion of butyrate-producing taxa (Clostridium-XIVa and Roseburia) and expansion of potentially pathogenic taxa within the Firmicutes and Proteobacteria phyla. Recovery of the gut microbial composition was incomplete two months after TPT. Robust clinical studies are necessary to comprehensively catalogue TPT-induced gut microbiota dysbiosis to inform strategies to mitigate potential long-term sequelae of this important TB control intervention.

Therapies for Parkinson's disease and the gut microbiome: evidence for bidirectional connection.

The gut brain axis (GBA), a bidirectional communication pathway has often been linked to health and disease, and gut microbiota (GM), a key component of this pathway shown to be altered in Parkinson's disease (PD), are suggested to contribute to the pathogenesis of PD. There are few studies that report the impact of oral medication therapy on GM, however, there are even fewer studies that discuss the impact of other treatments such as device assisted therapies (DAT) including deep brain stimulation (DBS), levodopa-carbidopa intestinal gel infusion (LCIG) and photobiomodulation (PBM) and how these might impact GM. Here, we review the literature and summarize findings of the potential contributions of GM to the heterogenous clinical response to pharmaceutical therapies among individuals with PD. We also discuss the potential interactions between the GM and DATs such as DBS and LCIG and present evidence for alterations in GM in response to DATs. Given the complexity and highly individual nature of the GM of patients with PD and the potential influence that other external factors such as diet, lifestyle, medications, stage of the disease and other comorbidities, further investigations into the response of GM to therapies are worthy of future study in prospective, controlled trials as well as medication naïve individuals. Such detailed studies will help us further comprehend the relationship between GM in PD patients, and will help investigate the potential of targeting GM associated changes as a treatment avenue for PD.

Associations of gut microbiome with endogenous estrogen levels in healthy postmenopausal women.

PURPOSE: The gut microbiome is a potentially important contributor to endogenous estrogen levels after menopause. In healthy postmenopausal women, we examined associations of fecal microbiome composition with levels of urinary estrogens, their metabolites, and relevant metabolic pathway ratios implicated in breast cancer risk. METHODS: Eligible postmenopausal women (n = 164) had a body mass index (BMI) ≤ 35 kg/m2 and no history of hormone use (previous 6 months) or cancer/metabolic disorders. Estrogens were quantified in spot urine samples with liquid chromatography-high resolution mass spectrometry (corrected for creatinine). Bacterial DNA was isolated from fecal samples and the V1-V2 hypervariable regions of 16S rRNA were sequenced on the Illumina MiSeq platform. We examined associations of gut microbiome's indices of within-sample (alpha) diversity (i.e., Shannon, Chao1, and Inverse Simpson), phylogenetic diversity, and the ratio of the two main phyla (Firmicutes and Bacteroidetes; F/B ratio) with individual estrogens and metabolic ratios, adjusted for age and BMI. RESULTS: In this sample of 164 healthy postmenopausal women, the mean age was 62.9 years (range 47.0-86.0). We found significant inverse associations of observed species with 4-pathway:total estrogens (p = 0.04) and 4-pathway:2-pathway (p = 0.01). Shannon index was positively associated with 2-catechols: methylated 2-catechols (p = 0.04). Chao1 was inversely associated with E1:total estrogens (p = 0.04), and 4-pathway:2-pathway (p = 0.02) and positively associated with 2-pathway:parent estrogens (p = 0.01). Phylogenetic diversity was inversely associated with 4-pathway:total estrogens (p = 0.02), 4-pathway:parent estrogens (p = 0.03), 4-pathway:2-pathway (p = 0.01), and 4-pathway:16-pathway (p = 0.03) and positively associated with 2-pathway:parent estrogens (p = 0.01). F/B ratio was not associated with any of the estrogen measures. CONCLUSION: Microbial diversity was associated with several estrogen metabolism ratios implicated in breast cancer risk. Further studies are warranted to confirm these findings in a larger and more representative sample of postmenopausal women, particularly with enrichment of minority participants.

16S rRNA gene sequencing of stool samples collected from patients with latent tuberculosis infection before, during, and two months after treatment with 3HP or 4R.

OBJECTIVE: We present 16s rRNA gene sequencing (V1-V2 region) and sample data from a pilot observational cohort study to describe the gut microbiota dynamics of subjects with latent tuberculosis infection (LTBI) treated with daily 600 mg rifampicin for four months (4R) or a weekly dose of 900 mg combination of rifapentine and isoniazid for three months (3HP). Our objectives were to (1) document changes to the gut microbiota immediately following exposure to the rifamycins and (2) document recovery to baseline two months after treatment completion. DATA DESCRIPTION: We enrolled six subjects with subjects with LTBI and prospectively followed them for 5-6 months. Each subject provided stool samples before, during, and two months after treatment. Six healthy controls were sampled in parallel with the patients with LTBIs. We report amplicon sequence variants (ASVs) and taxonomic assignments for 60 stool samples. Additionally, we provide access to the raw amplicon sequences, and subject responses to questionnaires about their diet, medication, and lifestyle changes over the study follow-up period. Furthermore, we provide the concentration of the parent and partially active rifamycin metabolite concentrations measured validated LC-MS-MS assays of phosphate buffer washes of the stool samples collected from the LTBI participants. This comprehensive dataset is a valuable resource for future systematic reviews and meta-analyses of the impact of LTBI therapy on the gut microbiota.

Resistant Maltodextrin Consumption in a Double-Blind, Randomized, Crossover Clinical Trial Induces Specific Changes in Potentially Beneficial Gut Bacteria.

Background: We have previously reported that the addition of resistant maltodextrin (RMD), a fermentable functional fiber, to the diet increases fecal weight as well as the amount of fecal bifidobacteria. Here, we report on the targeted analysis of changes in potentially beneficial gut bacteria associated with the intervention. Objective: The primary objective of this study was to determine the effect of adding 0, 15 and 25 g RMD to the diets of healthy free-living adults on potentially beneficial gut bacteria. Methods: We expanded on our previously reported microbiota analysis in a double-blind, placebo-controlled feeding study (NCT02733263) by performing additional qPCR analyses targeting fecal lactic acid bacteria (LAB), Akkermansia muciniphila, Faecalibacterium prausnitzii and Fusicatenibacter saccharivorans in samples from 49 participants. Results: RMD resulted in an approximately two-fold increase in fecal Fusicatenibacter saccharivorans (p = 0.024 for 15 g/day RMD and p = 0.017 for 25 g/day RMD). For Akkermansia muciniphila and Faecalibacterium prausnitzii, we obtained borderline evidence that showed increased amounts in participants that had low baseline levels of these bacteria (p < 0.1 for 25 g/day RMD). We did not detect any effects of RMD on LAB. Conclusions: RMD supplementation in healthy individuals increases Fusicatenibacter saccharivorans. Albeit to a lesser extent, RMD at the higher intake level may also increase Akkermansia muciniphila and Faecalibacterium prausnitzii in individuals with low baseline levels of those two species. Potential benefits associated with these microbiota changes remain to be established in studies with quantifiable health-related endpoints.

Associations between Vitamin D, Omega 6:Omega 3 Ratio, and Biomarkers of Aging in Individuals Living with and without Chronic Pain.

Elevated inflammatory cytokines and chronic pain are associated with shorter leukocyte telomere length (LTL), a measure of cellular aging. Micronutrients, such as 25-hydroxyvitamin D (vitamin D) and omega 3, have anti-inflammatory properties. Little is known regarding the relationships between vitamin D, omega 6:3 ratio, LTL, inflammation, and chronic pain. We investigate associations between vitamin D, omega 6:3 ratio, LTL, and C-reactive protein (CRP) in people living with/without chronic pain overall and stratified by chronic pain status. A cross-sectional analysis of 402 individuals (63% women, 79.5% with chronic pain) was completed. Demographic and health information was collected. Chronic pain was assessed as pain experienced for at least three months. LTL was measured in genomic DNA isolated from blood leukocytes, and micronutrients and CRP were measured in serum samples. Data were analyzed with general linear regression. Although an association between the continuous micronutrients and LTL was not observed, a positive association between omega 6:3 ratio and CRP was detected. In individuals with chronic pain, based on clinical categories, significant associations between vitamin D, omega 6:3 ratio, and CRP were observed. Findings highlight the complex relationships between anti-inflammatory micronutrients, inflammation, cellular aging, and chronic pain.

Meconium microbiota predicts clinical early-onset neonatal sepsis in preterm neonates.

BACKGROUND: Early-onset neonatal sepsis (EONS) remains one of the leading causes of morbidity and mortality related to premature birth, and its diagnosis remains difficult. Our goal was to evaluate the intestinal microbiota of the first meconium of preterm newborns and ascertain whether it is associated with clinical EONS. METHODS: In a controlled, prospective cohort study, samples of the first meconium of premature infants with a gestational age (GA) ≤32 weeks was obtained at Hospital de Clínicas de Porto Alegre and DNA was isolated from the samples. 16S rDNA based microbiota composition of preterm infants with a clinical diagnosis of EONS was compared to that of a control group. RESULTS: 40 (48%) premature infants with clinical diagnosis of EONS and 44 (52%) without EONS were included in the analysis. The most abundant phylum detected in both groups, Proteobacteria, was more prevalent in the sepsis group (p = .034). 14% of variance among bacterial communities (p = .001) correlated with EONS. The genera most strongly associated with EONS were Paenibacillus, Caulobacter, Dialister, Akkermansia, Phenylobacterium, Propionibacterium, Ruminococcus, Bradyrhizobium, and Alloprevotella. A single genus, Flavobacterium, was most strongly associated with the control group. CONCLUSION: These findings suggest that the first-meconium microbiota is different in preterm neonates with and without clinical EONS.

Effect of a Mediterranean diet intervention on gastrointestinal function in Parkinson's disease (the MEDI-PD study): study protocol for a randomised controlled trial.

INTRODUCTION: Constipation is a common and sometimes debilitating non-motor symptom of Parkinson's disease (PD) that can result in intestinal inflammation and microbial dysbiosis. The Mediterranean diet, rich in fermentable fibres and anti-inflammatory phenolic compounds, is associated with reduced risk of developing PD and slower progression of parkinsonism. The Mediterranean diet is often recommended for people with PD; however, no studies to date examine this diet as a therapeutic intervention to modulate gastrointestinal (GI) dysfunction. METHODS AND ANALYSIS: This is a randomised, controlled, parallel study. During a 2-week run-in, participants with PD and constipation symptoms (n=52) will undergo baseline nutritional and neurological assessments and provide a stool sample. Participants will be stratified by sex and Hoehn and Yahr stage and randomised to follow standard of care for constipation (control) or standard of care plus a Mediterranean diet (intervention) for 8 weeks. A study dietitian will provide dietary instruction and weekly follow-up via telephone to both groups to support adherence and monitor adverse events. Questionnaires will assess dietary intake and GI function including stool frequency, form, symptoms and laxative usage. Measurements completed at baseline will be repeated at 4 and 8 weeks of the intervention. The primary outcome is to evaluate the difference between mean change (final-baseline) in Gastrointestinal Symptom Rating Scale (GSRS) constipation syndrome scores for the control versus intervention groups. Secondary outcomes will assess stool frequency and form, weekly GSRS syndrome scores, digestive quality of life, laxative usage, faecal microbial communities and inflammatory markers, anxiety, depression, quality life, body weight and composition, dietary fibre intake and Mediterranean diet adherence. ETHICS AND DISSEMINATION: The study has received University of Florida Institutional Review Board-01 approval (IRB202001333). Findings will be disseminated via conference presentations, lectures and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT04683900.

Gut microbiome, body weight, and mammographic breast density in healthy postmenopausal women.

PURPOSE: We examined gut microbiome (GM) profiles in relation to mammographic breast density (BD) and body mass index (BMI) in healthy postmenopausal women. METHODS: Eligible women were postmenopausal, had a BMI ≤ 35 kg/m2, and had not recently taken oral/IV antibiotics. All women provided a fecal sample and information on breast cancer risk factors. Mammographic BD was classified with the American College of Radiology's BI-RADS BD classification system. Bacterial DNA was isolated from fecal samples and the V1-V2 hypervariable regions of 16S rRNA were sequenced on the Illumina MiSeq platform. We examined associations of GM with indices of within-sample (alpha) diversity and the ratio of the two main phyla (Firmicutes and Bacteroidetes; F/B ratio) with BD and BMI. RESULTS: Among 69 women with BD data, 39 had low BD (BI-RADS I/II) and 30 had high BD (BI-RADS III/IV). BMI was inversely associated with BD (mean BMI = 23.8 and 28.0 in women with high and low BD, respectively, p = 1.07 × 10-5). Similar levels of GM diversity were found across weight groups according to Shannon (p = 0.83); Inverse Simpson (p = 0.97); and Chao1 (p = 0.31) indices. F/B ratio and microbiota diversity were suggestively greater in women with high vs. low BD (p = 0.35, 0.14, 0.15, and 0.17 for F/B ratio, Shannon, Inverse Simpson and Chao1, respectively). CONCLUSION: Suggestive differences observed in women with high and low BD with respect to GM alpha diversity and prevalence of specific GM taxa need to be confirmed in larger studies.

Mediterranean Diet Adherence in People With Parkinson's Disease Reduces Constipation Symptoms and Changes Fecal Microbiota After a 5-Week Single-Arm Pilot Study.

Introduction: Non-motor symptoms of Parkinson's disease (PD) such as gastrointestinal (GI) dysfunction are common, yet little is known about how modifying dietary intake impacts PD symptoms. The aim of this study in individuals with PD was to determine whether a Mediterranean diet intervention is feasible and affects GI function, intestinal permeability and fecal microbial communities. Methods: A single-arm, 5-week Mediterranean diet intervention study was conducted in eight people with PD. Daily and weekly questionnaires were administered to determine changes in GI symptoms. Urine and stool samples were collected at baseline and after 5 weeks to assess intestinal permeability and fecal microbial communities. Additionally, live-in partners of the participants with PD were matched as controls (n = 8) for baseline urine and stool samples. Results: Participants with PD increased intake of Mediterranean diet based on adherence scores from baseline to week 5 (4.4 ± 0.6 vs. 11.9 ± 0.7; P < 0.01 with >10 representing good adherence), which was linked with weight loss (77.4 kg vs. 74.9 kg, P = 0.01). Constipation syndrome scores decreased after 5 weeks (2.3 ± 0.5 vs. 1.5 ± 0.3; P = 0.04). Bilophila, was higher at baseline in PD (0.6 ± 0.1% vs. 0.2 ± 0.1% P = 0.02) and slightly decreased after the diet intervention (0.5 ± 0.1%; P = 0.01). Interestingly, the proportion of Roseburia was significantly lower in PD compared to controls (0.6 ± 0.2% vs. 1.6 ± 0.3%; P = 0.02) and increased at week 5 (0.9 ± 0.2%; P < 0.01). No differences were observed for markers of intestinal permeability between the control and PD groups or post-intervention. Conclusions: Short-term Mediterranean diet adherence is feasible in participants with PD; correlated with weight loss, improved constipation, and modified gut microbiota. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT03851861.

The Gut-Brain Axis and Its Relation to Parkinson's Disease: A Review.

Parkinson's disease is a chronic neurodegenerative disease characterized by the accumulation of misfolded alpha-synuclein protein (Lewy bodies) in dopaminergic neurons of the substantia nigra and other related circuitry, which contribute to the development of both motor (bradykinesia, tremors, stiffness, abnormal gait) and non-motor symptoms (gastrointestinal issues, urinogenital complications, olfaction dysfunction, cognitive impairment). Despite tremendous progress in the field, the exact pathways and mechanisms responsible for the initiation and progression of this disease remain unclear. However, recent research suggests a potential relationship between the commensal gut bacteria and the brain capable of influencing neurodevelopment, brain function and health. This bidirectional communication is often referred to as the microbiome-gut-brain axis. Accumulating evidence suggests that the onset of non-motor symptoms, such as gastrointestinal manifestations, often precede the onset of motor symptoms and disease diagnosis, lending support to the potential role that the microbiome-gut-brain axis might play in the underlying pathological mechanisms of Parkinson's disease. This review will provide an overview of and critically discuss the current knowledge of the relationship between the gut microbiota and Parkinson's disease. We will discuss the role of α-synuclein in non-motor disease pathology, proposed pathways constituting the connection between the gut microbiome and the brain, existing evidence related to pre- and probiotic interventions. Finally, we will highlight the potential opportunity for the development of novel preventative measures and therapeutic options that could target the microbiome-gut-brain axis in the context of Parkinson's disease.

Gut Microbiota Dynamics in Parkinsonian Mice.

Peripheral immunity is thought to be dysregulated in Parkinson's disease (PD) and may provide an avenue for novel immunotherapeutic interventions. Gut microbiota is a potential factor for modulating immunotherapy response. Considering the possibly complex role of the gut-brain axis in PD, we used a preclinical model to determine the effects of gut microbiota dynamics in mice receiving an immunotherapeutic intervention compared to controls. A total of 17 M83 heterozygous transgenic mice were used in this study. Mice in the treatment arm (N = 10) received adoptive cellular therapy (ACT) by injection, and control mice (N = 7) were injected with saline at 8 weeks of age. All mice received peripheral α-syn fibrils to hasten parkinsonian symptoms via an intramuscular injection 1 week later (9 weeks of age; baseline). Fecal pellets were collected from all mice at three time points postinjection (baseline, 6 weeks, and 12 weeks). DNA from each stool sample was extracted, and 16S rDNA was amplified, sequenced, and analyzed using QIIME2 and RStudio. Differences in the relative abundance of bacterial taxa were observed over time between groups. No significant differences in alpha diversity were found between groups at any time point. UniFrac measures of phylogenetic distance between samples demonstrated distinct clustering between groups postbaseline (p = 0.002). These differences suggest that the gut microbiome may be capable of influencing immunotherapy outcomes. Conclusively, we observed distinctly different microbiota dynamics in treated mice compared to those in the control group. These results suggest a correlation between the gut-brain axis, PD pathology, and immunotherapy.

Microbiota composition in bilateral healthy breast tissue and breast tumors.

PURPOSE: Previous reports suggest that a complex microbiome exists within the female human breast that might contribute to breast cancer etiology. The purpose of this pilot study was to assess the variation in microbiota composition by breast side (left versus right) within individual women and compare the microbiota of normal and breast tumor tissue between women. We aimed to determine whether microbiota composition differs between these groups and whether certain bacterial taxa may be associated with breast tumors. METHODS: Bilateral normal breast tissue samples (n = 36) were collected from ten women who received routine mammoplasty procedures. Archived breast tumor samples (n = 10) were obtained from a biorepository. DNA was extracted, amplified, and sequenced. Microbiota data were analyzed using QIIME and RStudio. RESULTS: The most abundant phyla in both tumor and normal tissues were Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria. There were statistically significant differences in the relative abundance of various bacterial taxa between groups. Alpha diversity (Simpson's index) was significantly higher in normal compared to tumor samples (0.968 vs. 0.957, p = 0.022). Based on unweighted UniFrac measures, breast tumor samples clustered distinctly from normal samples (R2 = 0.130; p = 0.01). Microbiota composition in normal samples clustered within women (R2 = 0.394; p = 0.01) and by breast side (left or right) within a woman (R2 = 0.189; p = 0.03). CONCLUSION: Significant differences in diversity between tumor and normal tissue and in composition between women and between breasts of the same woman were identified. These results warrant further research to investigate the relationship between microbiota and breast cancer.

Under-the-Radar Dengue Virus Infections in Natural Populations of Aedes aegypti Mosquitoes.

The incidence of locally acquired dengue infections increased during the last decade in the United States, compelling a sustained research effort concerning the dengue mosquito vector, Aedes aegypti, and its microbiome, which has been shown to influence virus transmission success. We examined the "metavirome" of four populations of Aedes aegypti mosquitoes collected in 2016 to 2017 in Manatee County, FL. Unexpectedly, we discovered that dengue virus serotype 4 (DENV4) was circulating in these mosquito populations, representing the first documented case of such a phenomenon in the absence of a local DENV4 human case in this county over a 2-year period. We confirmed that all of the mosquito populations carried the same DENV4 strain, assembled its full genome, validated infection orthogonally by reverse transcriptase PCR, traced the virus origin, estimated the time period of its introduction to the Caribbean region, and explored the viral genetic signatures and mosquito-specific virome associations that potentially mediated DENV4 persistence in mosquitoes. We discuss the significance of prolonged maintenance of the DENV4 infections in A. aegypti that occurred in the absence of a DENV4 human index case in Manatee County with respect to the inability of current surveillance paradigms to detect mosquito vector infections prior to a potential local outbreak.IMPORTANCE Since 1999, dengue outbreaks in the continental United States involving local transmission have occurred only episodically and only in Florida and Texas. In Florida, these episodes appear to be coincident with increased introductions of dengue virus into the region through human travel and migration from countries where the disease is endemic. To date, the U.S. public health response to dengue outbreaks has been largely reactive, and implementation of comprehensive arbovirus surveillance in advance of predictable transmission seasons, which would enable proactive preventative efforts, remains unsupported. The significance of our finding is that it is the first documented report of DENV4 transmission to and maintenance within a local mosquito vector population in the continental United States in the absence of a human case during two consecutive years. Our data suggest that molecular surveillance of mosquito populations in high-risk, high-tourism areas of the United States may enable proactive, targeted vector control before potential arbovirus outbreaks.

A review of potential microbiome-gut-brain axis mediated neurocognitive conditions in persons living with HIV.

The microbiome-gut-brain axis, or the various interactions between the gut microbiome and the brain, has been of recent interest in the context of precision medicine research for a variety of disease states. Persons living with human immunodeficiency virus (PLWH) experience higher degrees of neurocognitive decline than the general population, correlating with a disruption of the normal gut microbiome composition (i.e. dysbiosis). While the nature of this correlation remains to be determined, there is the potential that the microbiome-gut-brain axis contributes to the progression of this disease. Previous research has established that the pathology associated with HIV induces alterations in the composition of gut microbiome, including a shift from Bacteroides to Prevotella dominance, and compromises gut barrier integrity, which may promote microbial translocation and consequent systemic inflammation and exacerbation of neuroinflammation. Further, though the use of antiretroviral therapy has been found to partially counteract HIV-related dysbiosis, it may also induce its own dysbiosis patterns, presenting a unique challenge for this research. More recent research has suggested the gut microbiome as a target for therapeutic interventions to improve symptoms associated with a variety of disease states, including HIV. Early findings are promising and warrant further research regarding the gut microbiome as a potential modifiable factor to improve health outcomes for PLWH. This review will discuss the current knowledge concerning the neuropathogenesis of HIV in the brain, role of the gut microbiome in neuroinflammation, and the relationship between HIV-status and the gut microbiome, followed by a conclusion that synthesizes this information within the context of the microbiome-gut-brain axis among PLWH. This review will also highlight the limitations of existing studies and propose future directions of this research.

Defining microbial biomarkers for risk of preterm labor.

Preterm birth remains the main contributor to early childhood mortality. The vaginal environment, including microbiota composition, might contribute to the risk of preterm delivery. Alterations in the vaginal microbial community structure might represent a risk factor for preterm birth. Here, we aimed to (a) investigate the association between preterm birth and the vaginal microbial community and (b) identify microbial biomarkers for risk of preterm birth. Microbial DNA was isolated from vaginal swabs in a cohort of 69 women enrolled at hospital admission for their delivery. Microbiota was analyzed by high-throughput 16S rRNA sequencing. While no differences in microbial diversity measures appeared associated with the spontaneous preterm and full-term outcomes, the microbial composition was distinct for these groups. Differential abundance analysis showed Lactobacillus species to be associated with full-term birth whereas an unknown Prevotella species was more abundant in the spontaneous preterm group. Although we studied a very miscegenated population from Brazil, our findings were similar to evidence pointed by other studies in different countries. The role of Lactobacillus species as a protector in the vaginal microbiome is demonstrated to be also a protector of spontaneous preterm outcome whereas the presence of pathogenic species, such as Prevotella spp., is endorsed as a factor of risk for spontaneous preterm delivery.

An Integrated Approach for Efficient Multi-Omics Joint Analysis.

The challenges associated with multi-omics analysis, e.g. DNA-seq, RNA-seq, metabolomics, methylomics and microbiomics domains, include: (1) increased high-dimensionality, as all -omics domains include ten thousands to hundreds of thousands of variables each; (2) increased complexity in analyzing domain-domain interactions, quadratic for pairwise correlation, and exponential for higher-order interactions; (3) variable heterogeneity, with highly skewed distributions in different units and scales for methylation and microbiome. Here, we developed an efficient strategy for joint-domain analysis, applying it to an analysis of correlations between colon epithelium methylomics and fecal microbiomics data with colorectal cancer risk as estimated by colorectal polyp prevalence. First, we applied domain-specific standard pipelines for quality assessment, cleaning, batch-effect removal, et cetera. Second, we performed variable homogenization for both the methylation and microbiome data sets, using domain-specific normalization and dimension reduction, obtaining scale-free variables that could be compared across the two domains. Finally, we implemented a joint-domain network analysis to identify relevant microbial-methylation island patterns. The network analysis considered all possible species-island pairs, thus being quadratic in its complexity. However, we were able to pre-select the unpaired variables by performing a preliminary association analysis on the outcome polyp prevalence. All results from association and interaction analyses were adjusted for multiple comparisons. Although the limited sample size did not provide good power (80% to detect medium to large effect sizes with 5% alpha error), a number of potentially significant association (dozens in the uncorrected analysis, reducing to just a few in the corrected one) were identified As a last step, we linked the network patterns identified by our approach to the KEGG functional ontology, showing that the method can generate new mechanistic hypotheses for the biological causes of polyp development.

The vaginal microbial communities of healthy expectant Brazilian mothers and its correlation with the newborn's gut colonization.

The female lower genital tract harbors a complex microbial community essential for homeostasis and health. During pregnancy, the female body undergoes unique hormonal changes that contribute to weight gain as well as modulations in immune function that can affect microbiota composition. Several studies have described the vaginal microbiota of pregnant women from the USA, Europe and Mexico. Here we expand our knowledge about the vaginal microbial communities during the third trimester to healthy expectant Brazilian mothers. Vaginal samples were collected from patients delivering at the Hospital de Clínicas de Porto Alegre, Brazil. Microbial DNA was isolated from samples and the V4 region of the 16S rRNA gene was amplified and sequenced using the PGM Ion Torrent. Brazilian pregnant women presented three distinct types of microbial community at the time of labor. Two microbial communities, Cluster 1 and Cluster 3, presented an overall dominance of Lactobacillus while Cluster 2 tended to present higher diversity and richness, with the presence of Pseudomonas, Prevotella and other vaginosis related bacteria. About half of the Brazilian mothers sampled here had dominance of L. iners. The proportion of mothers without dominance of any Lactobacillus was higher in Brazil (22%) compared to UK (2.4%) and USA, where this community type was not detected. The vaginal microbiota showed significant correlation with the composition of the babies' gut microbiota (p-value = 0.002 with a R2 of 15.8%). Mothers presenting different vaginal microbiota shared different microorganisms with their newborns, which would reflect on initial colonizers of the developing newborns' gut.