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.

Prevalent Multimorbidity Combinations Among Middle-Aged and Older Adults Seen in Community Health Centers.

BACKGROUND: Multimorbidity (≥ 2 chronic diseases) is associated with greater disability and higher treatment burden, as well as difficulty coordinating self-management tasks for adults with complex multimorbidity patterns. Comparatively little work has focused on assessing multimorbidity patterns among patients seeking care in community health centers (CHCs). OBJECTIVE: To identify and characterize prevalent multimorbidity patterns in a multi-state network of CHCs over a 5-year period. DESIGN: A cohort study of the 2014-2019 ADVANCE multi-state CHC clinical data network. We identified the most prevalent multimorbidity combination patterns and assessed the frequency of patterns throughout a 5-year period as well as the demographic characteristics of patient panels by prevalent patterns. PARTICIPANTS: The study included data from 838,642 patients aged ≥ 45 years who were seen in 337 CHCs across 22 states between 2014 and 2019. MAIN MEASURES: Prevalent multimorbidity patterns of somatic, mental health, and mental-somatic combinations of 22 chronic diseases based on the U.S. Department of Health and Human Services Multiple Chronic Conditions framework: anxiety, arthritis, asthma, autism, cancer, cardiac arrhythmia, chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), congestive heart failure, coronary artery disease, dementia, depression, diabetes, hepatitis, human immunodeficiency virus (HIV), hyperlipidemia, hypertension, osteoporosis, post-traumatic stress disorder (PTSD), schizophrenia, substance use disorder, and stroke. KEY RESULTS: Multimorbidity is common among middle-aged and older patients seen in CHCs: 40% have somatic, 6% have mental health, and 24% have mental-somatic multimorbidity patterns. The most frequently occurring pattern across all years is hyperlipidemia-hypertension. The three most frequent patterns are various iterations of hyperlipidemia, hypertension, and diabetes and are consistent in rank of occurrence across all years. CKD-hyperlipidemia-hypertension and anxiety-depression are both more frequent in later study years. CONCLUSIONS: CHCs are increasingly seeing more complex multimorbidity patterns over time; these most often involve mental health morbidity and advanced cardiometabolic-renal morbidity.

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.

The impact of capitated payment on preventive care utilization in community health clinics.

Only half of the United States population regularly receives recommended preventive care services. Alternative payment models (e.g., a per-member-per-month capitated payment model) may encourage the delivery of preventive services when compared to a fee-for-service visitbased model; however, evaluation is lacking in the United States. This study assesses the impact of implementing Oregon's Alternative Payment Methodology (APM) on orders for preventive services within community health centers (CHCs). This retrospective cohort study uses electronic health record data from the OCHIN, Inc., 2012-2018, analyzed in 2018-2019. Twenty-seven CHCs which implemented APM in 2013-2016 were compared to six non-APM CHCs. Clinic-level quarterly rates of ordering nine preventive services in 2012-2018 were calculated. For each phase and preventive service, we used difference-in-differences analysis to assess the APM impact on ordering preventive care. We found greater increases for APM CHCs compared to non-APM CHCs for orders of mammograms (difference-in-differences estimates (DDs) across four phases:1.69-2.45). Both groups had decreases in ordering cervical cancer screenings, however, APM CHCs had smaller decreases (DDs:1.62-1.93). The APM CHCs had significantly greater decreases in influenza vaccinations (DDs:0.17-0.32). There were no consistent significant differences in pre-post changes in APM vs. non-APM CHCs for cardiometabolic risk screenings, smoking status and depression assessments. There was nonsignificant change in the proportion of nontraditional encounters in APM clinics compared to controls. Transition from fee-for-service to an APM did not negatively impact delivery of preventive care. Further studies are needed to understand how to change encounter structures to best deliver recommended preventive care.

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.

Dietary raisin intake has limited effect on gut microbiota composition in adult volunteers.

BACKGROUND: Dried fruits, such as raisins, contain phytochemicals and dietary fibers that contribute to maintaining health, potentially at least partially through modification in gut microbiota composition and activities. However, the effects of raisin consumption on gut microbiota have not previously been thoroughly investigated in humans. Therefore, the objective of this study was to determine how adding three servings of sun dried raisin/day to the diet of healthy volunteers affects gut microbiota composition. METHODS: A 14-day exploratory feeding study was conducted with thirteen healthy individuals between the ages of 18 and 59 years. Participants consumed three servings (28.3 g each) of sun dried raisins daily. Fecal samples were collected prior to raisin consumption (baseline) and after the addition of raisins to the diet (on days 7 and 14). To determine the effects of raisin intake, fecal microbiota composition before and after raisin consumption was characterized for each participant by 16S rRNA gene sequencing. RESULTS: Overall microbiota diversity was not significantly affected by adding raisins to the diet. However, upon addition of raisins to the diet specific OTUs matching Faecalibacterium prausnitzii, Bacteroidetes sp. and Ruminococcus sp. increased in prevalence while OTUs closest to Klebsiella sp., Prevotella sp. and Bifidobacterium spp. decreased. CONCLUSION: Our findings suggest that adding raisins to the diet can affect the prevalence of specific bacterial taxa. Potential health benefits of the observed microbiota changes should be determined in future studies in populations for which specific health outcomes can be targeted. TRIAL REGISTRATION: http://www.clinicaltrials.gov ; Identifier: NCT02713165 .

Novel encapsulation improves recovery of probiotic strains in fecal samples of human volunteers.

Probiotic supplements can contribute to maintaining health and ameliorating various disease symptoms. Probiotics can be delivered in many forms with crucial differences in their survival during gastrointestinal (GI) passage. Previously, a novel encapsulation, Probiotic Pearls™ Acidophilus, Integrative Therapeutics, LLC, USA (Pearls), was shown to increase survival in vitro after exposure to gastric conditions. Here, we compare fecal recovery in human volunteers consuming Pearls or a conventional hard-shelled gelatin capsule. We performed a randomized double-blinded, two-armed trial, with six healthy subjects in each 12-day study arm. In fecal samples collected at baseline, twice during the intervention period, and after washout, we compared colony counts between the two encapsulation methods. The identity of the colonies was confirmed by colony morphology, strain-specific PCR, and 16S rRNA gene sequencing. We further performed a comprehensive 16S rRNA gene sequencing-based analysis to identify differential effects on overall microbiota composition. We detected an average log increase in bifidobacteria of 0.152 cfu/g with gelatin and 0.651 cfu/g with Pearls capsules (p > 0.05). Total lactobacilli counts increased in both groups with no difference between the groups. However, the supplemented Lactobacillus acidophilus NCFM decreased to baseline levels within 7 days after end of supplementation with gelatin capsules while 3.11 log cfu/g higher counts compared to baseline (p = 0.05) remained for Pearls. Targeted qPCR largely confirmed the trends observed by viable plate counts. Protecting the probiotic strains by Pearls encapsulation results in higher recovery rates of the supplemented lactobacilli and bifidobacteria in fecal samples and increased persistence, suggesting an improved survival and viability that might increase efficacy towards achieving desired health benefits.

Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and Bifidobacterium longum MM-2 Ingestion Induces a Less Inflammatory Cytokine Profile and a Potentially Beneficial Shift in Gut Microbiota in Older Adults: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study.

OBJECTIVE: This study determined whether older adults who consumed a probiotic mixture would have a greater proportion of circulating CD4+ lymphocytes, altered cytokine production, and a shift in intestinal microbiota toward a healthier microbial community. METHODS: Participants (70 ± 1 years [mean ± SEM]; n = 32) consumed a probiotic (Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and Bifidobacterium longum MM2) or a placebo twice daily for 3 weeks with a 5-week washout period between intervention periods. Blood and stools were collected before and after each intervention. The percentage of circulating CD4+ lymphocytes and ex vivo mitogen-stimulated cell cytokine production were measured. In stools, specific bacterial targets were quantified via quantitative polymerase chain reaction (qPCR) and community composition was determined via pyrosequencing. RESULTS: During the first period of the crossover the percentage of CD4+ cells decreased with the placebo (48% ± 3% to 31% ± 3%, p < 0.01) but did not change with the probiotic (44% ± 3% to 42% ± 3%) and log-transformed concentrations of interleukin-10 increased with the probiotic (1.7 ± 0.2 to 3.4 ± 0.2, p < 0.0001) but not the placebo (1.7 ± 0.2 to 2.1 ± 0.2). With the probiotic versus the placebo a higher percentage of participants had an increase in fecal bifidobacteria (48% versus 30%, p < 0.05) and lactic acid bacteria (55% versus 43%, p < 0.05) and a decrease in Escherichia coli (52% versus 27%, p < 0.05). Several bacterial groups matching Faeacalibactierium prausnitzii were more prevalent in stool samples with the probiotic versus placebo. CONCLUSIONS: The probiotic maintained CD4+ lymphocytes and produced a less inflammatory cytokine profile possibly due to the changes in the microbial communities, which more closely resembled those reported in healthy younger populations.

Halogenated Phenazines that Potently Eradicate Biofilms, MRSA Persister Cells in Non-Biofilm Cultures, and Mycobacterium tuberculosis.

Conventional antibiotics are ineffective against non-replicating bacteria (for example, bacteria within biofilms). We report a series of halogenated phenazines (HP), inspired by marine antibiotic 1, that targets persistent bacteria. HP 14 demonstrated the most potent biofilm eradication activities to date against MRSA, MRSE, and VRE biofilms (MBEC = 0.2-12.5 µM), as well as the effective killing of MRSA persister cells in non-biofilm cultures. Frontline MRSA treatments, vancomycin and daptomycin, were unable to eradicate MRSA biofilms or non-biofilm persisters alongside 14. HP 13 displayed potent antibacterial activity against slow-growing M. tuberculosis (MIC = 3.13 µM), the leading cause of death by bacterial infection around the world. HP analogues effectively target persistent bacteria through a mechanism that is non-toxic to mammalian cells and could have a significant impact on treatments for chronic bacterial infections.

The metabolizable energy of dietary resistant maltodextrin is variable and alters fecal microbiota composition in adult men.

Resistant maltodextrin (RM) is a novel soluble, nonviscous dietary fiber. Its metabolizable energy (ME) and net energy (NE) values derived from nutrient balance studies are unknown, as is the effect of RM on fecal microbiota. A randomized, placebo-controlled, double-blind crossover study was conducted (n = 14 men) to determine the ME and NE of RM and its influence on fecal excretion of macronutrients and microbiota. Participants were assigned to a sequence consisting of 3 treatment periods [24 d each: 0 g/d RM + 50 g/d maltodextrin and 2 amounts of dietary RM (25 g/d RM + 25 g of maltodextrin/d and 50 g/d RM + 0 g/d maltodextrin)] and were provided all the foods they were to consume to maintain their body weight. After an adaptation period, excreta were collected during a 7-d period. After the collection period, 24-h energy expenditure was measured. Fluorescence in situ hybridization, quantitative polymerase chain reaction, and 454 titanium technology-based 16S rRNA sequencing were used to analyze fecal microbiota composition. Fecal amounts of energy (544, 662, 737 kJ/d), nitrogen (1.5, 1.8, 2.1 g/d), RM (0.3, 0.6, 1.2 g/d), and total carbohydrate (11.1, 14.2, 16.2 g/d) increased with increasing dose (0, 25, 50 g) of RM (P < 0.0001). Fat excretion did not differ among treatments. The ME value of RM was 8.2 and 10.4 kJ/g, and the NE value of RM was -8.2 and 2.0 kJ/g for the 25 and 50 g/d RM doses, respectively. Both doses of RM increased fecal wet weight (118, 148, 161 g/d; P < 0.0001) and fecal dry weight (26.5, 32.0, 35.8 g/d; P < 0.0001) compared with the maltodextrin placebo. Total counts of fecal bacteria increased by 12% for the 25 g/d RM dose (P = 0.17) and 18% for the 50 g/d RM dose (P = 0.019). RM intake was associated with statistically significant increases (P < 0.001) in various operational taxonomic units matching closest to ruminococcus, eubacterium, lachnospiraceae, bacteroides, holdemania, and faecalibacterium, implicating RM in their growth in the gut. Our findings provide empirical data important for food labeling regulations related to the energy value of RM and suggest that RM increases fecal bulk by enhancing the excretion of nitrogen and carbohydrate and the growth of specific microbial populations.

Effects of almond and pistachio consumption on gut microbiota composition in a randomised cross-over human feeding study.

The modification of microbiota composition to a 'beneficial' one is a promising approach for improving intestinal as well as overall health. Natural fibres and phytochemicals that reach the proximal colon, such as those present in various nuts, provide substrates for the maintenance of healthy and diverse microbiota. The effects of increased consumption of specific nuts, which are rich in fibre as well as various phytonutrients, on human gut microbiota composition have not been investigated to date. The objective of the present study was to determine the effects of almond and pistachio consumption on human gut microbiota composition. We characterised microbiota in faecal samples collected from volunteers in two separate randomised, controlled, cross-over feeding studies (n 18 for the almond feeding study and n 16 for the pistachio feeding study) with 0, 1·5 or 3 servings/d of the respective nuts for 18 d. Gut microbiota composition was analysed using a 16S rRNA-based approach for bacteria and an internal transcribed spacer region sequencing approach for fungi. The 16S rRNA sequence analysis of 528 028 sequence reads, retained after removing low-quality and short-length reads, revealed various operational taxonomic units that appeared to be affected by nut consumption. The effect of pistachio consumption on gut microbiota composition was much stronger than that of almond consumption and included an increase in the number of potentially beneficial butyrate-producing bacteria. Although the numbers of bifidobacteria were not affected by the consumption of either nut, pistachio consumption appeared to decrease the number of lactic acid bacteria (P< 0·05). Increasing the consumption of almonds or pistachios appears to be an effective means of modifying gut microbiota composition.

Survey of culture, goldengate assay, universal biosensor assay, and 16S rRNA Gene sequencing as alternative methods of bacterial pathogen detection.

Cultivation-based assays combined with PCR or enzyme-linked immunosorbent assay (ELISA)-based methods for finding virulence factors are standard methods for detecting bacterial pathogens in stools; however, with emerging molecular technologies, new methods have become available. The aim of this study was to compare four distinct detection technologies for the identification of pathogens in stools from children under 5 years of age in The Gambia, Mali, Kenya, and Bangladesh. The children were identified, using currently accepted clinical protocols, as either controls or cases with moderate to severe diarrhea. A total of 3,610 stool samples were tested by established clinical culture techniques: 3,179 DNA samples by the Universal Biosensor assay (Ibis Biosciences, Inc.), 1,466 DNA samples by the GoldenGate assay (Illumina), and 1,006 DNA samples by sequencing of 16S rRNA genes. Each method detected different proportions of samples testing positive for each of seven enteric pathogens, enteroaggregative Escherichia coli (EAEC), enterotoxigenic E. coli (ETEC), enteropathogenic E. coli (EPEC), Shigella spp., Campylobacter jejuni, Salmonella enterica, and Aeromonas spp. The comparisons among detection methods included the frequency of positive stool samples and kappa values for making pairwise comparisons. Overall, the standard culture methods detected Shigella spp., EPEC, ETEC, and EAEC in smaller proportions of the samples than either of the methods based on detection of the virulence genes from DNA in whole stools. The GoldenGate method revealed the greatest agreement with the other methods. The agreement among methods was higher in cases than in controls. The new molecular technologies have a high potential for highly sensitive identification of bacterial diarrheal pathogens.

Chronic overlapping pain conditions and long-term opioid treatment.

OBJECTIVES: One in 5 people in the United States lives with chronic pain. Many patients with chronic pain experience a subset of specific co-occurring pain conditions that may share a common pain mechanism and that have been designated as chronic overlapping pain conditions (COPCs). Little is known about chronic opioid prescribing patterns among patients with COPCs in primary care settings, especially among socioeconomically vulnerable patients. This study aims to evaluate opioid prescribing among patients with COPCs in US community health centers and to identify individual COPCs and their combinations that are associated with long-term opioid treatment (LOT). STUDY DESIGN: Retrospective cohort study. METHODS: We conducted analyses of more than 1 million patients 18 years and older based on electronic health record data from 449 US community health centers across 17 states between January 1, 2009, and December 31, 2018. Logistic regression models were used to assess the relationship between COPCs and LOT. RESULTS: Individuals with COPCs were prescribed LOT 4 times more often than individuals without a COPC (16.9% vs 4.0%). The presence of chronic low back pain, migraine headache, fibromyalgia, or irritable bowel syndrome combined with any of the other COPCs increased the odds of LOT prescribing compared with the presence of a single COPC. CONCLUSIONS: Although LOT prescribing has declined over time, it remains relatively high among patients with certain COPCs and for those with multiple COPCs. These study findings suggest target populations for future interventions to manage chronic pain among socioeconomically vulnerable patients.

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.

Curated and harmonized gut microbiome 16S rRNA amplicon data from dietary fiber intervention studies in humans.

Next generation amplicon sequencing has created a plethora of data from human microbiomes. The accessibility to this scientific data and its corresponding metadata is important for its reuse, to allow for new discoveries, verification of published results, and serving as path for reproducibility. Dietary fiber consumption has been associated with a variety of health benefits that are thought to be mediated by gut microbiota. To enable direct comparisons of the response of the gut microbiome to fiber, we obtained 16S rRNA sequencing data and its corresponding metadata from 11 fiber intervention studies for a total of 2,368 samples. We provide curated and pre-processed genetic data and common metadata for comparison across the different studies.

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.

Are there sex differences in potentially inappropriate prescribing in adults with multimorbidity?

BACKGROUND/OBJECTIVES: Limited knowledge exists regarding sex differences in prescribing potentially inappropriate medications (PIMs) for various multimorbidity patterns. This study sought to determine sex differences in PIM prescribing in older adults with cardiovascular-metabolic patterns. DESIGN: Retrospective cohort study. SETTING: Health and Retirement Study (HRS) 2004-2014 interview data, linked to HRS-Medicare claims data annualized for 2005-2014. STUDY SAMPLE: Six thousand three-hundred and forty-one HRS participants aged 65 and older with two and more chronic conditions. MEASUREMENTS: PIM events were calculated using 2015 American Geriatrics Society Beers Criteria. Multimorbidity patterns included: "cardiovascular-metabolic only," "cardiovascular-metabolic plus other physical conditions," "cardiovascular-metabolic plus mental conditions," and "no cardiovascular-metabolic disease" patterns. Logistic regression models were used to determine the association between PIM and sex, including interaction between sex and multimorbidity categories in the model, for PIM overall and for each PIM drug class. RESULTS: Women were prescribed PIMs more often than men (39.4% vs 32.8%). Overall, women had increased odds of PIM (Adj. odds ratio [OR] = 1.30, 95% confidence interval [CI]: 1.16-1.46). Women had higher odds of PIM than men with cardiovascular-metabolic plus physical patterns (Adj. OR = 1.25, 95% CI: 1.07-1.45) and cardiovascular-metabolic plus mental patterns (Adj. OR = 1.25, 95% CI: 1.06-1.48), and there were no sex differences in adults with a cardiovascular-metabolic only patterns (Adj. OR = 1.13, 95% CI: 0.79-1.62). Women had greater odds of being prescribed the following PIMs: anticholinergics, antidepressants, antispasmodics, benzodiazepines, skeletal muscle relaxants, and had lower odds of being prescribed pain drugs and sulfonylureas compared with men. CONCLUSION: This study evaluated sex differences in PIM prescribing among adults with complex cardiovascular-metabolic multimorbidity patterns. The effect of sex varied across multimorbidity patterns and by different PIM drug classes. This study identified important opportunities for future interventions to improve medication prescribing among older adults at risk for PIM.

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.

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.

Uptake of Preventive Services Among Patients With and Without Multimorbidity.

INTRODUCTION: Patients with multiple chronic conditions (multimorbidity) are seen commonly in primary care practices and often have suboptimal uptake of preventive care owing to competing treatment demands. The complexity of multimorbidity patterns and their impact on receiving preventive services is not fully understood. This study identifies multimorbidity combinations associated with low receipt of preventive services. METHODS: This was a retrospective cohort study of U.S. community health center patients aged ≥19 years. Electronic health record data from 209 community health centers for the January 1, 2014-December 31, 2017 study period were analyzed in 2018-2019. Multimorbidity patterns included physical only, mental health only, and physical and mental health multimorbidity patterns, with no multimorbidity as a reference category. Electronic health record-based preventive ratios (number of months services were up-to-date/total months the patient was eligible for services) were calculated for the 14 preventive services. Negative binomial regression models assessed the relationship between multimorbidity physical and/or mental health patterns and the preventive ratio for each service. RESULTS: There was a variation in receipt of preventive care between multimorbidity groups: individuals with mental health only multimorbidity were less likely to be up-to-date with cardiometabolic and cancer screenings than the no multimorbidity group or groups with physical health conditions, and the physical only multimorbidity group had low rates of depression screening. CONCLUSIONS: This study provided critical insights into receipt of preventive service among adults with multimorbidity using a more precise method for measuring up-to-date preventive care delivery. Findings would be useful to identify target populations for future intervention programs to improve preventive care.