Explore the vast range of titles available.

Those with mild cognitive impairment (MCI), a precursor to dementia, have a gut microbiome distinct from healthy individuals, but this has only been shown in healthy individuals, not in those exhibiting several risk factors for dementia. Using amplicon 16S rRNA gene sequencing in a case-control study of 60 older (ages 55–76), obese, predominately female, African American adults, those with MCI (cases) had different gut microbiota profiles than controls. While microbial community diversity was similar between cases and controls, the abundances of specific microbial taxa weren’t, such as Parabacteroides distasonis (lower in cases) and Dialister invisus (higher in cases). These differences disappeared after adjusting for markers of oxidative stress and systemic inflammation. Cognitive scores were positively correlated with levels of Akkermansia muciniphila , a bacterium associated with reduced inflammation. Our study shows that gut microbial composition may be associated with inflammation, oxidative stress, and MCI in those at high risk for dementia.

We compared the gut microbial populations in 100 women, from rural Ghana and urban US [50% lean (BMI < 25 kg/m 2 ) and 50% obese (BMI ≥ 30 kg/m 2 )] to examine the ecological co-occurrence network topology of the gut microbiota as well as the relationship of short chain fatty acids (SCFAs) with obesity. Ghanaians consumed significantly more dietary fiber, had greater microbial alpha-diversity, different beta-diversity, and had a greater concentration of total fecal SCFAs (p-value < 0.002). Lean Ghanaians had significantly greater network density, connectivity and stability than either obese Ghanaians, or lean and obese US participants (false discovery rate (FDR) corrected p-value ≤ 0.01). Bacteroides uniformis was significantly more abundant in lean women, irrespective of country (FDR corrected p < 0.001), while lean Ghanaians had a significantly greater proportion of Ruminococcus callidus , Prevotella copri , and Escherichia coli , and smaller proportions of Lachnospiraceae, Bacteroides and Parabacteroides . Lean Ghanaians had a significantly greater abundance of predicted microbial genes that catalyzed the production of butyric acid via the fermentation of pyruvate or branched amino-acids, while obese Ghanaians and US women (irrespective of BMI) had a significantly greater abundance of predicted microbial genes that encoded for enzymes associated with the fermentation of amino-acids such as alanine, aspartate, lysine and glutamate. Similar to lean Ghanaian women, mice humanized with stool from the lean Ghanaian participant had a significantly lower abundance of family Lachnospiraceae and genus Bacteroides and Parabacteroides , and were resistant to obesity following 6 - weeks of high fat feeding (p-value < 0.01). Obesity-resistant mice also showed increased intestinal transcriptional expression of the free fatty acid ( Ffa ) receptor Ffa2 , in spite of similar fecal SCFAs concentrations. We demonstrate that the association between obesity resistance and increased predicted ecological connectivity and stability of the lean Ghanaian microbiota, as well as increased local SCFA receptor level, provides evidence of the importance of robust gut ecologic network in obesity.

In vitro ovarian follicle culture is an active area of research towards providing fertility options for survivors of childhood cancer. Late-stage murine follicles (multilayer secondary and onwards) can be cultured successfully to maturity to obtain a meiotically competent oocyte for fertilization, but primordial and primary follicles usually die in culture because many key components of early follicle development are still unknown and difficult to mimic in vitro. To engineer a biomimetic three-dimensional culture system with high efficacy and reproducibility for the clinic, detailed mechanisms of early folliculogenesis must be uncovered. Previous studies have shown that primary murine follicles co-cultured in groups, in contrast to single follicles cultured in isolation, can reach preovulatory size and produce competent oocytes, but the factors accounting for the synergy of follicle co-culture are still unknown. To probe the underlying mechanisms of successful follicle co-culture, we conducted a time-course experiment for murine follicles encapsulated in 0.3% alginate hydrogels and compared between two conditions: groups of 5 (5X) versus groups of 10 (10X). For every 2 days during the course of 12 days, follicles were dissociated and somatic cells were isolated for microarray-based gene expression analysis (n = 380 follicles for 5X and n = 430 follicles for 10X). Gene activities in follicles co-cultured in larger groups (10X) had a distinct transcriptomic profile of key genes and pathways such as prolactin signaling and angiogenesis-related genes when compared to cells from follicles co-cultured in the smaller cohort (5X). To benchmark the results for follicles grown in culture, we compared our microarray data to data from murine follicles freshly isolated from the ovary at comparable stages of development previously published by Bernabé et al. Comparison of these datasets identified similarities and differences between folliculogenesis in the native microenvironment and the engineered in vitro system. A more detailed understanding of follicle growth in vitro will not only allow for better culture methods but also advance the field towards providing improved fertility options for survivors of childhood cancer.

Perinatal perceived stress can contribute to worse health outcomes for the parent–child dyad. Given the emerging relationship between the microbiota-gut-brain axis and stress, this study sought to elucidate connections between bowel symptoms and the gut microbiome in relation to perceived stress at three time points in the perinatal period: two during pregnancy and one postpartum. Ninety-five pregnant individuals participated in a prospective cohort study from April 2017 to November 2019. Researchers assessed Perceived Stress Scale-10 (PSS); bowel symptoms (according to the IBS Questionnaire); psychiatrist assessment of new onset or exacerbated depression and anxiety; and fecal samples analyzed for alpha diversity (measures of gut microbiome diversity utilizing Shannon, Observed OTUs, and Faith’s PD) at each timepoint. Covariates included weeks of gestation and weeks postpartum. PSS scores were divided into “Perceived Self-Efficacy” and “Perceived Helplessness.” Increased gut microbial diversity was associated with decreased bowel symptoms, decreased overall perceived stress, increased ability to cope with adversity, and decreased distress in the postpartum period. This study found a significant association between a less diverse microbial community, lower self-efficacy early in pregnancy, and greater bowel symptoms and perceived helplessness later in the perinatal period, relationships that may ultimately point to novel diagnostic methods and interventions for perceived stress based on the microbiota-gut-brain axis.

Background: The optimization of treatment for pediatric cancer has increased 5-year survivor rates to over 80%. Currently, there are almost half a million survivors of a pediatric cancer alive in the United States, with numbers increasing worldwide. Despite increased survivorship, pediatric cancer survivors (PCSs) are at high risk for long-term chronic disease, including cardiometabolic dysregulation at an early age due to cancer-related treatments. PCSs often have increased adiposity, perturbation in the gut microbiome, and chronic systemic inflammation compared to age-matched controls. Time-restricted eating (TRE) has emerged as an effective dietary intervention to promote weight loss in individuals with increased adiposity and cardiometabolic disease. Prebiotic supplements may enhance the efficacy of TRE by promoting satiety via the gut microbiome. Given the accessibility of both TRE and prebiotic supplements, this type of dietary intervention may be ideal for young adult PCSs. The purpose of this study was to determine the feasibility and acceptability of 12 weeks of TRE with and without a prebiotic supplement among young adult PCSs. Changes in body weight, body composition, and cardiometabolic disease risk markers were explored. Methods: Feasibility was measured based on recruitment (n = 20), retention (>80%), and adherence to the TRE eating window and prebiotic (>80%), and acceptability was measured based on a validated survey. Body weight, body composition, blood pressure, and additional blood-based cardiometabolic disease risk markers were also measured before and following the intervention. Results: Feasibility was not met based on recruitment (n = 13), but retention and adherence exceeded the a priori hypothesis. Acceptability also met the a priori hypothesis. Improvements were observed in some cardiometabolic disease risk markers, including a significant decrease in fat mass and visceral fat mass in both groups following the intervention. Conclusions: Given the positive outcomes related to retention, adherence, and acceptability, as well as some cardiometabolic disease risk markers, a larger and longer study of TRE and prebiotic supplementation in PCSs is warranted. However, innovative recruitment strategies should be implemented, such as leveraging social media and targeting larger geographical areas, given recruitment challenges.

Perinatal depression is the most common complication of pregnancy and affects the mother, fetus, and infant. Recent preclinical studies and a limited number of clinical studies have suggested an influence of the gut microbiome on the onset and course of mental health disorders. In this review, we examine the current state of knowledge regarding genetics, epigenetics, heritability, and neuro-immuno-endocrine systems biology in perinatal mood disorders, with a particular focus on the interaction between these factors and the gut microbiome, which is mediated via the gut-brain axis. We also provide an overview of experimental and analytical methods that are currently available to researchers interested in elucidating the influence of the gut microbiome on mental health disorders during pregnancy and postpartum.

BackgroundCompared with traditional screening questionnaires, computerised adaptive tests for severity of depression (CAT-DI) and computerised adaptive diagnostic modules for depression (CAD-MDD) show improved precision in screening for major depressive disorder. CAT measures have been tailored to perinatal women but have not been studied in low-income women of colour despite high rates of perinatal depression (PND).ObjectiveThis study aimed to examine the concordance between CAT and traditional measures of depression in a sample of primarily low-income black and Latina women.MethodsIn total, 373 women (49% black; 29% Latina) completed the Patient Health Questionnaire-9 (PHQ-9), CAD-MDD and CAT-DI at 845 visits across pregnancy and postpartum. We examined the concordance between continuous CAT-DI and PHQ-9 scores and between binary measures of PND diagnosis on CAD-MDD and the PHQ-9 (cut-off score >10). We examined cases with a positive PND diagnosis on the CAD-MDD but not on the PHQ-9 (‘missed’ cases) to determine whether clinic notes were consistent with CAD-MDD results.FindingsCAT-DI and PHQ-9 scores were significantly associated (concordance correlation coefficient=0.67; 95% CI 0.58 to 0.74). CAD-MDD detected 5% more case of PND compared with PHQ-9 (p<0.001). The average per-visit rate of PND was 14.4% (14.5% in blacks, 14.9% in Latinas) on the CAD-MDD, and 9.5% (9.8% in blacks, 8.8% in Latinas) on the PHQ-9. Clinical notes were available on 60% of ‘missed’ cases and validated CAD-MDD PND diagnosis in 89% of cases.ConclusionsCAD-MDD detected 5% more cases of PND in women of colour compared with traditional tests, and the majority of these cases were verified by clinician notes.Clinical implicationsUse of CAT in routine clinic care may address health disparities in PND screening.

The proximal colon and cecum are two intestinal regions in which the microbiome localizes to two spatially distinct compartments, the lumen and crypts. The differences in composition and function of luminal and crypt microbiome in the cecum and the effect of physiological stress on their compartmentalization remain poorly characterized. Here, we characterized the composition and function of the lumen-, mucus-, and crypt-associated microbiome in the cecum of mice. We observed a highly ordered microbial architecture within the cecum whose assembly and function become markedly disrupted when provoked by physiological stress such as surgery and its attendant preoperative treatments (i.e., overnight fasting and antibiotics). Major shifts in local physicochemical cues including a decrease in hypoxia levels, an increase in pH, and a loss of butyrate production were associated with the loss of compositional and functional compartmentalization of the cecal microbiome. The cecum is a unique region in the mammalian intestinal tract in which the microbiome is localized to two compartments, the lumen and the crypts. The microbiome within crypts is particularly important as it is in direct contact with lining epithelial cells including stem cells. Here, we analyzed the microbiome in cecum of mice using multiple techniques including metagenomics. The lumen microbiome comprised Firmicutes and Bacteroidetes whereas the crypts were dominated by Proteobacteria and Deferribacteres , and the mucus comprised a mixture of these 4 phyla. The lumen microbial functional potential comprised mainly carbon metabolism, while the crypt microbiome was enriched for genes encoding stress resistance. In order to determine how this structure, assembly, and function are altered under provocative conditions, we exposed mice to overnight starvation (S), antibiotics (A), and a major surgical injury (partial hepatectomy [H]), as occurs with major surgery in humans. We have previously demonstrated that the combined effect of this “SAH” treatment leads to a major disturbance of the cecal microbiota at the bottom of crypts in a manner that disrupts crypt cell homeostasis. Here, we applied the SAH conditions and observed a loss of compartmentalization in both composition and function of the cecal microbiome associated with major shifts in local physicochemical cues including decrease of hypoxia, increase of pH, and loss of butyrate production. Taken together, these studies demonstrated a defined order, structure, and function of the cecal microbiome that can be disrupted under provocative conditions such as major surgery and its attendant exposures. IMPORTANCE The proximal colon and cecum are two intestinal regions in which the microbiome localizes to two spatially distinct compartments, the lumen and crypts. The differences in composition and function of luminal and crypt microbiome in the cecum and the effect of physiological stress on their compartmentalization remain poorly characterized. Here, we characterized the composition and function of the lumen-, mucus-, and crypt-associated microbiome in the cecum of mice. We observed a highly ordered microbial architecture within the cecum whose assembly and function become markedly disrupted when provoked by physiological stress such as surgery and its attendant preoperative treatments (i.e., overnight fasting and antibiotics). Major shifts in local physicochemical cues including a decrease in hypoxia levels, an increase in pH, and a loss of butyrate production were associated with the loss of compositional and functional compartmentalization of the cecal microbiome.

Oral and fecal microbial biomarkers have previously been associated with cardiometabolic (CM) risk, however, no comprehensive attempt has been made to explore this association in minority populations or across different geographic regions. We characterized gut- and oral-associated microbiota and CM risk in 655 participants of African-origin, aged 25-45, from Ghana, South Africa, Jamaica, and the United States (US). CM risk was classified using the CM risk cut-points for elevated waist circumference, elevated blood pressure and elevated fasted blood glucose, low high-density lipoprotein (HDL), and elevated triglycerides. Gut-associated bacterial alpha diversity negatively correlated with elevated blood pressure and elevated fasted blood glucose. Similarly, gut bacterial beta diversity was also significantly differentiated by waist circumference, blood pressure, triglyceridemia and HDL-cholesterolemia. Notably, differences in inter- and intra-personal gut microbial diversity were geographic-region specific. Participants meeting the cut-points for 3 out of the 5 CM risk factors were significantly more enriched with Lachnospiraceae, and were significantly depleted of Clostridiaceae, Peptostreptococcaceae, and Prevotella. The predicted relative proportions of the genes involved in the pathways for lipopolysaccharides (LPS) and butyrate synthesis were also significantly differentiated by the CM risk phenotype, whereby genes involved in the butyrate synthesis via lysine, glutarate and 4-aminobutyrate/succinate pathways and LPS synthesis pathway were enriched in participants with greater CM risk. Furthermore, inter-individual oral microbiota diversity was also significantly associated with the CM risk factors, and oral-associated Streptococcus, Prevotella, and Veillonella were enriched in participants with 3 out of the 5 CM risk factors. We demonstrate that in a diverse cohort of African-origin adults, CM risk is significantly associated with reduced microbial diversity, and the enrichment of specific bacterial taxa and predicted functional traits in both gut and oral environments. As well as providing new insights into the associations between the gut and oral microbiota and CM risk, this study also highlights the potential for novel therapeutic discoveries which target the oral and gut microbiota in CM risk.

Early-onset colorectal cancer (EOCRC) is defined as a diagnosis of colorectal cancer (CRC) in individuals younger than 50 years of age. While overall CRC rates in the United States (US) decreased between 2001 and 2018, EOCRC rates have increased. This research project aims to evaluate the feasibility and acceptability of Time-Restricted Eating (TRE), Mindfulness, or TRE combined with Mindfulness among young to middle-aged adults at risk of EOCRC. Forty-eight participants will be randomly assigned to one of four groups: TRE, Mindfulness, TRE and Mindfulness, or Control. Data on feasibility, adherence, and acceptability will be collected. Measures assessed at baseline and post-intervention will include body weight, body composition, dietary intake, physical activity, sleep behavior, circulating biomarkers, hair cortisol, and the gut microbiome. The effects of the intervention on the following will be examined: (1) acceptability and feasibility; (2) body weight, body composition, and adherence to TRE; (3) circulating metabolic, inflammation, and oxidative stress biomarkers; (4) intestinal inflammation; and (5) the gut microbiome. TRE, combined with Mindfulness, holds promise for stress reduction and weight management among individuals at risk of EOCRC. The results of this pilot study will inform the design and development of larger trials aimed at preventing risk factors associated with EOCRC.