Alpha Diversity Of Gut Microbiome Research Articles

P139 THE GUT MICROBIOME AS A PREDICTOR OF INCIDENT HYPERTENSION: DATA FROM A POPULATION SAMPLE OF 3055 INDIVIDUALS WITH A FOLLOW-UP OF 20 YEARS

Background and Objective: Our goal was to examine the previously unknown long-term association between gut microbiome composition and incident hypertension in a representative population cohort. Methods: We collected fecal samples from a population sample of 3,055 non-hypertensive Finns (mean age 43.1 years; 60.8% women) in 2002. These individuals were followed up for incident hypertension until 31 December 2021 using nationwide register data. The samples were sequenced using shotgun metagenomics. We examined associations between gut microbiome composition and incident hypertension using Cox regression (alpha diversity and microbial taxa), permutational multivariate ANOVA (beta diversity) and Analysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC; microbial taxa) models adjusted for conventional hypertension risk factors. Results: Altogether, 587 cases of incident diabetes occurred over the median follow-up of 19.8 years. Gut microbiome alpha diversity (Shannon index; p=0.98) and beta diversity (R2=0.49%; p=0.99) were not associated with incident hypertension. Furthermore, the associations between microbial taxa and incident hypertension were non-significant. In Cox regression models (Figure), two species reached an FDR-corrected P-value <0.1: Eubacterium G Ventriosum (hazard ratio per 1-SD increase 0.89; 95% CI 0.83-0.96; P=0.07) and Hespellia Stercorisuis (hazard ratio 1.16; 95% CI 1.05-1.27; P=0.098). In ANCOM-BC models, three species reached an FDR corrected P-value of <0.1: Merdousia sp000438015 (log2 fold change 0.32±0.09; P=0.06), Mitsuokella multacida (log2 fold change -0.32±0.09; P=0.06), and Scybalousia sp900543675 (log2 fold change -0.28±0.09; P=0.07). Conclusions: In this first-ever analysis on the association between the gut microbiome and long-term hypertension incidence, we observed that the associations between overall gut taxonomic composition and incident hypertension are weak. In addition, only a few microbial taxa reached a borderline level of significance with inconsistent results between two statistical methods. These findings suggest that the gut microbiome is not a strong predictor of future hypertension.

Pristine and UV-aged polyethylene microplastics’ impact on gut microbiome and reproduction of earthworm Eisenia andrei

The impact of microplastics (MPs) on soil organisms is still a growing field, yet very little is known about the exposure of ultraviolet (UV) aging of MPs to soil organisms. In this study, we explored the response of the epigeic earthworm Eisenia andrei to pristine and UV-aged polyethylene (PE-MP) exposure at a wide range of environmentally relevant concentrations (0, 0.2, 2, 20, 200 and 2000 mg kg−1) in an organic farm soil for 56d and assessed changes in reproduction, ingestion, egestion and gut microbiome. Results showed that exposure to 20 mg kg−1 pristine PE-MP significantly increased earthworm reproduction by 39 % but the same concentration decreased reproduction by 29 % when they were exposed to UV-aged PE-MP. Ingestion of PE was verified by staining the whole worm body and their casts after 48h of starvation. The amounts of PE-MP found in the body and the casts were positively correlated with PE-MP concentrations in the soil, however only significantly so with pristine PE-MP. A decline in E. andrei gut microbiome alpha diversity and a significantly different community composition were observed in UV-aged PE-MP exposures compared to pristine PE-MP. Relative to the control treatments, Proteobacteria increased up to 135 %, Actinobacteria increased up to 35 %, and Firmicutes decreased up to 38 % under UV-aged PE-MP exposure, whereas Cyanobacteria increased up to 19 times in the pristine PE-MP treatments. These results confirm the negative effect of UV-aged PE-MP on earthworms even at low concentrations and could have important implications in the well-functioning of agricultural soils.

Gut microbiome and inflammation among athletes in wheelchair in a crossover randomized pilot trial of probiotic and prebiotic interventions

Disorders related to gut health are a significant cause of morbidity among athletes in wheelchair. This pilot feasibility trial aims to investigate whether probiotics compared to prebiotics can improve inflammatory status and gut microbiome composition in elite athletes in wheelchair. We conducted a 12-week, randomized, cross-over controlled trial involving 14 elite Swiss athletes in wheelchair. Participants were given a multispecies-multistrain probiotic or prebiotic (oat bran) daily for 4 weeks (Clinical trials.gov NCT04659408 09/12/2020). This was followed by a 4-week washout and then crossed over. Thirty inflammatory markers were assessed using bead-based multiplex immunoassays (LegendPlex) from serum samples. The gut microbiome was characterized via 16S rRNA sequencing of stool DNA samples. Statistical analyses were conducted using linear mixed-effect models (LMM). At baseline, most athletes (10/14) exhibited low levels of inflammation which associated with higher gut microbiome alpha diversity indices compared to those with high inflammation levels. The use of probiotic had higher decrease in 25 (83%) inflammatory markers measured compared to prebiotic use. Probiotic has the potential in lowering inflammation status and improving the gut microbiome diversity. The future trial should focus on having sufficient sample sizes, population with higher inflammation status, longer intervention exposure and use of differential abundance analysis.

Association of maternal genetics with the gut microbiome and eucalypt diet selection in captive koalas.

Koalas, an Australian arboreal marsupial, depend on eucalypt tree leaves for their diet. They selectively consume only a few of the hundreds of available eucalypt species. Since the koala gut microbiome is essential for the digestion and detoxification of eucalypts, their individual differences in the gut microbiome may lead to variations in their eucalypt selection and eucalypt metabolic capacity. However, research focusing on the relationship between the gut microbiome and differences in food preferences is very limited. We aimed to determine whether individual and regional differences exist in the gut microbiome of koalas as well as the mechanism by which these differences influence eucalypt selection. Foraging data were collected from six koalas and a total of 62 feces were collected from 15 koalas of two zoos in Japan. The mitochondrial phylogenetic analysis was conducted to estimate the mitochondrial maternal origin of each koala. In addition, the 16S-based gut microbiome of 15 koalas was analyzed to determine the composition and diversity of each koala's gut microbiome. We used these data to investigate the relationship among mitochondrial maternal origin, gut microbiome and eucalypt diet selection. This research revealed that diversity and composition of the gut microbiome and that eucalypt diet selection of koalas differs among regions. We also revealed that the gut microbiome alpha diversity was correlated with foraging diversity in koalas. These individual and regional differences would result from vertical (maternal) transmission of the gut microbiome and represent an intraspecific variation in koala foraging strategies. Further, we demonstrated that certain gut bacteria were strongly correlated with both mitochondrial maternal origin and eucalypt foraging patterns. Bacteria found to be associated with mitochondrial maternal origin included bacteria involved in fiber digestion and degradation of secondary metabolites, such as the families Rikenellaceae and Synergistaceae. These bacteria may cause differences in metabolic capacity between individual and regional koalas and influence their eucalypt selection. We showed that the characteristics (composition and diversity) of the gut microbiome and eucalypt diet selection of koalas differ by individuals and regional origins as we expected. In addition, some gut bacteria that could influence eucalypt foraging of koalas showed the relationships with both mitochondrial maternal origin and eucalypt foraging pattern. These differences in the gut microbiome between regional origins may make a difference in eucalypt selection. Given the importance of the gut microbiome to koalas foraging on eucalypts and their strong symbiotic relationship, future studies should focus on the symbiotic relationship and coevolution between koalas and the gut microbiome to understand individual and regional differences in eucalypt diet selection by koalas.

Abstract 6204: Differential gut microbiome alpha diversity in endometrial and ovarian carcinoma patients

Abstract Background: Emerging research underscores the gut microbiome's critical role in cancer development, progression, and response to treatment. As a part of the “ASAP” study, which focuses on the implementation of comprehensive molecular profiling and deep clinical annotation of electronic health records in participants diagnosed with or at risk of developing cancer, we have established a microbiome-associated biobank and corresponding clinical dataset to systematically explore the dynamics of the gut microbiome as patients progress through cancer treatment. We describe a pilot project where we explore the baseline microbiome samples collected from ASAP participants, particularly from those with endometrial and ovarian carcinomas. Methods: Stool samples from patients were collected at the time of enrollment in the ASAP study and sampling is repeated every three months to align with the additional biosampling procedures. Microbial DNA was extracted from the baseline stool samples and subjected to sequencing of the V4 region of the 16S rRNA gene. After generating species level operational taxonomic units (OTUs), alpha diversity measures were generated in the form of the inverse Simpson index. In order to determine whether there was a difference in alpha diversity between individuals with ovarian (N = 37) and endometrial (N = 35) carcinomas, we employed a t-test with 100,000 permutations to derive an empirical p-value. Results: We present sequencing results from the initial n=297 samples. Our comparison of the alpha diversity between ASAP study participants with ovarian and endometrial carcinomas showed a significant difference between the two groups, with the ovarian cancer patients having a lower alpha diversity (empirical p-value = 0.03915). Due to the uniform sampling, biobanking, and analytical procedures, our study allows the ability to explore microbiome features amongst various cancer diagnoses while minimizing laboratory and analytical differences that plague microbiome reproducibility. Conclusions: We observed a significant difference in alpha diversity between patients with endometrial and ovarian carcinomas. Although the current results are preliminary, the wealth of information available in the ASAP protocol will allow us to continue exploring the association of the gut microbiome with cancer and the associated treatment. Citation Format: Casey T. Finnicum, Tobias Meissner, Christel Davis, Sarah Viet, Jason L. Petersen, McKenna Deaton, Benjamin Solomon, William Spanos, David Starks, Rachel Elsey, Erik A. Ehli, Casey Williams. Differential gut microbiome alpha diversity in endometrial and ovarian carcinoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6204.

Premature Infant Gut Microbiome relationships with childhood behavioral scales: preliminary insights.

Very Low Birth Weight (VLBW) infants, born weighing less than 1,500 grams, are at risk for both gut dysbiosis and later neuropsychological developmental deficits. Behavioral effects, while related to neurodevelopment, are often more subtle and difficult to measure. The extent of later neurobehavioral consequences associated with such microbial dysbiosis has yet to be determined. We explored associations between the infants' gut microbiome and early childhood behavior at 4 years of age and identified the bacterial taxa through a multivariate analysis by linear models. Parents completed the Child Behavior Checklist (CBCL) focused on different DSM diagnostic categories: affective, anxiety, pervasive developmental, attention deficit/hyperactivity, and oppositional defiant. All the CBCL scores were corrected for gender, delivery method, gestational age, infant birth weight, occurrence of sepsis, and days on antibiotics prior statistical analyses. Canonical correlation analysis (CCA) was performed to determine the relationship between early life gut microbiome and the adjusted CBCL scores. The association of bacterial Amplicon sequence Variants (ASVs) to the CBCL scores were tested with multivariate analysis by linear models (MaAsLin). Nineteen children who were previously born with very low birth weight and studied while hospitalized in the Neonatal Intensive Care Unit (NICU) were included in this study. Statistically significant associations were observed between early life gut bacteria such as Veillonella dispar, Enterococcus, Escherichia coli, and Rumincococcus to later behavior at 4 years. No significant association could be observed with early-life gut microbiome alpha diversity and behavioral measures at 4 years. These preliminary observational data provide insight into the relationships between VLBW gut microbiome dysbiosis and childhood behavior. This study contributes to the literature on gut microbiome analysis by examining various behavioral domains using a standardized tool linked to the Diagnostic and Statistical Manual of Mental Disorders (DSM).

Fulfilled Mind, Healthy Gut? Relationships of Eudaimonic Psychological Well-Being With the Gut Microbiome in Postmenopausal Women.

Eudaimonic facets of psychological well-being (PWB), like purpose in life and sense of mastery, are associated with healthy aging. Variation in the gut microbiome may be one pathway by which mental health influences age-related health outcomes. However, associations between eudaimonic PWB and the gut microbiome are understudied. We examined whether purpose in life and sense of mastery, separately, were associated with features of the gut microbiome in older women. Participants were from the Mind-Body Study ( N = 206, mean age = 61 years), a substudy of the Nurses' Health Study II cohort. In 2013, participants completed the Life Engagement Test and the Pearlin Mastery Scale. Three months later, up to two pairs of stool samples were collected, 6 months apart. Covariates included sociodemographics, depression, health status, and health behaviors. Analyses examined associations of PWB with gut microbiome taxonomic diversity, overall community structure, and specific species/pathways. To account for multiple testing, statistical significance was established using Benjamini-Hochberg adjusted p values (i.e., q values ≤0.25). We found no evidence of an association between PWB and gut microbiome alpha diversity. In multivariate analysis, higher purpose levels were significantly associated with lower abundance of species previously linked with poorer health outcomes, notably Blautia hydrogenotrophica and Eubacterium ventriosum ( q values ≤0.25). No significant associations were found between PWB and metabolic pathways. These findings offer early evidence suggesting that eudaimonic PWB is linked with variation in the gut microbiome, and this might be one pathway by which PWB promotes healthy aging.

Island biogeography theory provides a plausible explanation for why larger vertebrates and taller humans have more diverse gut microbiomes.

Prior work has shown a positive scaling relationship between vertebrate body size, human height, and gut microbiome alpha diversity. This observation mirrors commonly observed species area relationships (SARs) in many other ecosystems. Here, we expand these observations to several large datasets, showing that this size-diversity scaling relationship is independent of relevant covariates, like diet, body mass index, age, sex, bowel movement frequency, antibiotic usage, and cardiometabolic health markers. Island biogeography theory (IBT), which predicts that larger islands tend to harbor greater species diversity through neutral demographic processes, provides a simple mechanism for positive SARs. Using a gut-adapted IBT model, we demonstrated that increasing the length of a flow-through ecosystem led to increased species diversity, closely matching our empirical observations. We delve into the possible clinical implications of these SARs in the American Gut cohort. Consistent with prior observations that lower alpha diversity is a risk factor for Clostridioides difficile infection (CDI), we found that individuals who reported a history of CDI were shorter than those who did not and that this relationship was mediated by alpha diversity. We observed that vegetable consumption had a much stronger association with CDI history, which was also partially mediated by alpha diversity. In summary, we find that the positive scaling observed between body size and gut alpha diversity can be plausibly explained by a gut-adapted IBT model, may be related to CDI risk, and vegetable intake appears to independently mitigate this risk, although additional work is needed to validate the potential disease risk implications.

Gut microbiome alpha diversity decreases in relation to body weight, antibiotic exposure, and infection with multidrug-resistant organisms

The human gastrointestinal tract is home to a dense and diverse microbiome, predominated by bacteria. Despite the conservation of critical functionality across most individuals, the composition of the gut microbiome is highly individualized, leading to differential responses to perturbations such as oral antibiotics or multidrug-resistant organism (MDRO) infection. Herein, subject responses to these perturbations based on their body weight were evaluated. Fecal samples were collected from 45 subjects at the Detroit Medical Center to evaluate the effects of perturbations on subjects' gut microbiome composition. Bacterial profiling was completed using 16S rRNA gene sequencing. Subjects with multiple MDROs, subjects weighing greater than 80kg infected with MDRO E coli, and subjects weighing less than 80kg with exposure to vancomycin and carbapenem antibiotics during hospitalization had significantly decreased gut microbiome richness. Both administration of oral antibiotics and MDRO infections decreased gut microbiome alpha diversity, but the magnitude of these gut microbiome perturbations was body weight dependent.

Ramen Consumption and Gut Microbiota Diversity in Japanese Women: Cross-Sectional Data from the NEXIS Cohort Study.

A cross-sectional study involving 224 healthy Japanese adult females explored the relationship between ramen intake, gut microbiota diversity, and blood biochemistry. Using a stepwise regression model, ramen intake was inversely associated with gut microbiome alpha diversity after adjusting for related factors, including diets, Age, BMI, and stool habits (β = -0.018; r = -0.15 for Shannon index). The intake group of ramen was inversely associated with dietary nutrients and dietary fiber compared with the no-intake group of ramen. Sugar intake, Dorea as a short-chain fatty acid (SCFA)-producing gut microbiota, and γ-glutamyl transferase as a liver function marker were directly associated with ramen intake after adjustment for related factors including diets, gut microbiota, and blood chemistry using a stepwise logistic regression model, whereas Dorea is inconsistently less abundant in the ramen group. In conclusion, the increased ramen was associated with decreased gut bacterial diversity accompanying a perturbation of Dorea through the dietary nutrients, gut microbiota, and blood chemistry, while the methodological limitations existed in a cross-sectional study. People with frequent ramen eating habits need to take measures to consume various nutrients to maintain and improve their health, and dietary management can be applied to the dietary feature in ramen consumption.

Exploring the characteristics of gut microbiome in patients of Southern Fujian with hypocitraturia urolithiasis and constructing clinical diagnostic models.

Hypocitraturia is an important cause of urolithiasis. Exploring the characteristics of the gut microbiome (GMB) of hypocitriuria urolithiasis (HCU) patients can provide new ideas for the treatment and prevention of urolithiasis. The 24h urinary citric acid excretion of 19 urolithiasis patients was measured, and patients were divided into the HCU group and the normal citrate urolithiasis (NCU) group. The 16s ribosomal RNA (rRNA) was used to detect GMB composition differences and construct operational taxonomic units (OTUs) coexistence networks. The key bacterial community was determined by Lefse analysis, Metastats analysis and RandomForest analysis. Redundancy analysis (RDA) and Pearson correlation analysis visualized the correlation between key OTUs and clinical features and then established the disease diagnosis model of microbial-clinical indicators. Finally, PICRUSt2 was used to explore the metabolic pathway of related GMB in HCU patients. The alpha diversity of GMB in HCU group was increased and Beta diversity analysis suggested significant differences between HCU and NCU groups, which was related to renal function damage and urinary tract infection. Ruminococcaceae_ge and Turicibacter are the characteristic bacterial groups of HCU. Correlation analysis showed that the characteristic bacterial groups were significantly associated with various clinical features. Based on this, the diagnostic models of microbiome-clinical indicators in HCU patients were constructed with the areas under the curve (AUC) of 0.923 and 0.897, respectively. Genetic and metabolic processes of HCU are affected by changes in GMB abundance. GMB disorder may be involved in the occurrence and clinical characteristics of HCU by influencing genetic and metabolic pathways. The new microbiome-clinical indicator diagnostic model is effective.

Diet, Gut Microbiome, and Their End Metabolites Associate With Acute Pancreatitis Risk.

Diet and decreased gut microbiome diversity has been associated with acute pancreatitis (AP) risk. However, differences in dietary intake, gut microbiome, and their impact on microbial end metabolites have not been studied in AP. We aimed to determine differences in (i) dietary intake (ii) gut microbiome diversity and sulfidogenic bacterial abundance, and (iii) serum short-chain fatty acid (SCFA) and hydrogen sulfide (H 2 S) concentrations in AP and control subjects. This case-control study recruited 54 AP and 46 control subjects during hospitalization. Clinical and diet data and stool and blood samples were collected. 16S rDNA sequencing was used to determine gut microbiome alpha diversity and composition. Serum SCFA and H 2 S levels were measured. Machine learning (ML) model was used to identify microbial targets associated with AP. AP patients had a decreased intake of vitamin D 3 , whole grains, fish, and beneficial eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids. AP patients also had lower gut microbiome diversity ( P = 0.021) and a higher abundance of sulfidogenic bacteria including Veillonella sp. and Haemophilus sp., which were associated with AP risk. Serum acetate and H 2 S concentrations were significantly higher in the AP group ( P < 0.001 and P = 0.043, respectively). ML model had 96% predictive ability to distinguish AP patients from controls. AP patients have decreased beneficial nutrient intake and gut microbiome diversity. An increased abundance of H 2 S-producing genera in the AP and SCFA-producing genera in the control group and predictive ability of ML model to distinguish AP patients indicates that diet, gut microbiota, and their end metabolites play a key role in AP.

The Role of Gut Microbiota in Various Neurological and Psychiatric Disorders-An Evidence Mapping Based on Quantified Evidence.

We searched PubMed, Cochrane Library, and Epistemonikos to identify systematic reviews and meta-analysis (SRs). We searched for neurological diseases and psychiatric disorders, including Alzheimer's disease (AD), attention deficit hyperactivity disorder (ADHD), amyotrophic lateral sclerosis (ALS), autism spectrum disorder (ASD), anorexia nervosa (AN), bipolar disorder (BD), eating disorder (ED), generalized anxiety disorder (GAD), major depressive disorder (MDD), multiple sclerosis (MS), obsessive compulsive disorder (OCD), Parkinson's disease (PD), posttraumatic stress disorder (PTSD), spinal cord injury (SCI), schizophrenia, and stroke. We used A Measurement Tool to Assess Systematic Reviews (AMSTAR-2) to evaluate the quality of included SRs. We also created an evidence map showing the role of gut microbiota in neurological diseases and the certainty of the evidence. In total, 42 studies were included in this evidence mapping. Most findings were obtained from observational studies. According to the AMSTAR-2 assessment, 21 SRs scored "critically low" in terms of methodological quality, 16 SR scored "low," and 5 SR scored "moderate." A total of 15 diseases have been investigated for the potential association between gut microbiome alpha diversity and disease, with the Shannon index and Simpson index being the most widely studied. A total of 12 diseases were investigated for potential link between beta diversity and disease. At the phylum level, Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, and Verrucomicrobia were more researched. At the genus level, Prevotella, Coprococcus, Parabacteroides, Phascolarctobacterium, Escherichia Shigella, Alistipes, Sutteralla, Veillonella, Odoribacter, Faecalibacterium, Bacteroides, Bifidobacterium, Dialister, and Blautia were more researched. Some diseases have been found to have specific flora changes, and some diseases have been found to have common intestinal microbiological changes. We found varied levels of evidence for the associations between gut microbiota and neurological diseases; some gut microbiota increased the risk of neurological diseases, whereas others showed evidence of benefit that gut microbiota might be promising therapeutic targets for such diseases.

Choline supplementation regulates gut microbiome diversity, gut epithelial activity, and the cytokine gene expression in gilts.

Choline is an essential nutrient that is necessary for both fetal development and maintenance of neural function, while its effect on female ovarian development is largely unexplored. Our previous study demonstrated that choline supplementation promotes ovarian follicular development and ovulation, although its underlying mechanism was unclear. To uncover the potential regulation pathway, eighteen female Yorkshire × Landrace gilts were fed with either standard commercial diet (Control group, n = 9) or choline supplemented diet (Choline group, additional 500 mg/kg of control diet, n = 9) from day 90 of age to day 186. At day 186, feces samples were analyzed for effects on the gut microbiome using 16S ribosomal RNA gene V3-V4 region sequencing with Illumina MiSeq, serum samples were analyzed for trimethylamine (TMA) and trimethylamine-N-oxide (TMAO) using HILIC method, and jejunum tissues were analyzed for immune related gene expression using qRT-PCR. Our results show that choline supplementation did not alter the circulating level of TMA and TMAO (P > 0.05), but rather increased gut microbiome alpha diversity (P < 0.05). Beta diversity analysis results showed that the choline diet mainly increased the abundance of Firmicutes, Proteobacteria, and Actinobacteria, but decreased the abundance of Bacteroidetes, Spirochaetes, and Euryarchaeota at the phyla level. Meta-genomic analysis revealed that choline supplementation activated pathways in the gut microbiota associated with steroid hormone biosynthesis and degradation of infertility-causing environmental pollutants (bisphenol, xylene, and dioxins). To further verify the effect of choline on intestinal activity, a porcine intestine cell line (IPEC-J2) was treated with serial concentrations of choline chloride in vitro. Our data demonstrated that choline promoted the proliferation of IPEC-J2 while inhibiting the apoptotic activity. qRT-PCR results showed that choline significantly increased the expression level of Bcl2 in both IPEC-J2 cells and jejunum tissues. The expression of IL-22, a cytokine that has been shown to impact ovarian function, was increased by choline treatment in vitro. Our findings reveal the beneficial effect of choline supplementation on enhancing the gut microbiome composition and intestinal epithelial activity, and offer insights into how these changes may have contributed to the ovarian development-promoting effect we reported in our previous study.

Адипокины и миокины как индикаторы фенотипов ожирения и их связь с показателями разнообразия микробиома кишечника

Today, metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) are distinguished. Adipose and muscle tissues can determine the obese phenotype due to adipokine and myokine production. Gut microbial community is also involved in MHO. The study was aimed to reveal the features of adipokine and myokine levels and their association with the gut microbiome alpha diversity in patients with MHO and MUO. A total of 265 subjects were divided into two groups: healthy individuals and obese patients. The latter were divided into two subgroups: patients with MHO and patients with MUO. Body mass index, waist circumference, HOMA-IR, adipokine and myokine levels, gut microbiome taxonomic composition, alpha diversity indices were defined in all the surveyed individuals, lipid and carbohydrate metabolism was also assessed. Significant differences in the adipokine and myokine levels and their association with the gut microbiome diversity indicators were revealed in patients with different obese phenotypes. Patients with MHO and MUO showed significantly lower adiponectin levels (р &lt; 0.05) and significantly higher leptin and asprosin levels (р &lt; 0.05) than healthy individuals. Patients with MUO had lower adiponectin and leptin levels (p &lt; 0.05) than patients with MHO. Significantly higher FGF21 levels were observed in patients with MUO. Large-scale correlation analysis revealed the relationship between the glucose levels and the gut microbiome diversity indices that was missing in patients with MUO. This indicated the loss of the microbiota diversity effects on the blood glucose control in individuals with MUO, as well as different regulatory roles in the gut microbiome‒liver‒muscle/adipose tissue axes of individuals with MHO and MUO played by gut microbiota. The findings show the relationship between the gut microbiome diversity and the obese phenotype.

Association between inflammation, lipopolysaccharide binding protein, and gut microbiota composition in a New Hampshire Bhutanese refugee population with a high burden of type 2 diabetes.

South Asian refugees experience a high risk of obesity and diabetes yet are often underrepresented in studies on chronic diseases and their risk factors. The gut microbiota and gut permeability, as assessed through circulating lipopolysaccharide binding protein (LBP), may underlie the link between chronic inflammation and type 2 diabetes (T2D). The composition of the gut microbiota varies according to multiple factors including demographics, migration, and dietary patterns, particularly fiber intake. However, there is no evidence on the composition of the gut microbiota and its relationship with metabolic health in refugee populations, including those migrating to the United States from Bhutan. The objective of this study was to examine glycemic status in relation to LBP, systemic inflammation fiber intake, and gut microbiota composition in Bhutanese refugee adults residing in New Hampshire (n = 50). This cross-sectional study included a convenience sample of Bhutanese refugee adults (N = 50) in NH. Established bioinformatics pipelines for metagenomic analysis were used to determine relative genus abundance, species richness, and alpha diversity measures from shallow shotgun sequences. The relationships between inflammatory markers, gut microbiota composition, dietary fiber, and glycemic status were analyzed. We identified a substantial chronic disease burden in this study population, and observed a correlation between glycemic status, LBP, and inflammation, and a correlation between glycemic status and gut microbiome alpha diversity. Further, we identified a significant correlation between proinflammatory taxa and inflammatory cytokines. SCFA-producing taxa were found to be inversely correlated with age. To date, this is the most comprehensive examination of metabolic health and the gut microbiome in a Bhutanese refugee population in NH. The findings highlight areas for future investigations of inflammation and glycemic impairment, in addition to informing potential interventions targeting this vulnerable population.

Global landscape of gut microbiome diversity and antibiotic resistomes across vertebrates

Multiple factors influence gut microbiome diversity in vertebrate hosts. Most previous studies have only investigated specific factors and certain host species or taxa. However, a comprehensive assessment of the relative contributions of individual factors towards gut microbial diversity within a broader evolutionary context remains lacking. Here, 2202 16S rRNA gene sequencing samples of gut bacterial communities collected from 452 host species across seven classes were analyzed together to understand the factors broadly affecting vertebrate gut microbiomes across hosts with different diets, threatened status, captivity status, and habitat environmental factors. Among wild vertebrates, diet was most significantly associated with gut microbiome alpha diversity, while host phylogeny and diet were significantly associated with beta diversity, consistent with a previous study. Host threatened status and habitat environmental factors (e.g., geography and climate) were also associated with gut bacterial community beta diversity. Subsequent ecological modeling revealed a strong association between stochastic assembly processes and patterns of gut bacterial diversity among free-ranging vertebrates. In addition, metagenomic analysis of gut microbiomes from 62 captive vertebrates and sympatric humans revealed similar diversity and resistome profiles despite differences in host phylogeny, diet, and threatened status. These results thus suggest that captivity diminishes the effects of host phylogeny, diet, and threatened status on the diversity of vertebrate gut bacterial communities. The most overrepresented antibiotic resistant genes (ARGs) observed in these samples are involved in resistance to β-lactams, aminoglycosides, and tetracycline. These results also revealed potential horizontal transfers of ARGs between captive animals and humans, thereby jointly threatening public health and vertebrate conservation. Together, this study provides a comprehensive overview of the diversity and resistomes of vertebrate gut microbiomes. These combined analyses will help guide future vertebrate conservation via the rational manipulation of microbial diversity and reducing antibiotic usage.

NMR Metabolomics Reveal Urine Markers of Microbiome Diversity and Identify Benzoate Metabolism as a Mediator between High Microbial Alpha Diversity and Metabolic Health.

Microbial metabolites measured using NMR may serve as markers for physiological or pathological host–microbe interactions and possibly mediate the beneficial effects of microbiome diversity. Yet, comprehensive analyses of gut microbiome data and the urine NMR metabolome from large general population cohorts are missing. Here, we report the associations between gut microbiota abundances or metrics of alpha diversity, quantified from stool samples using 16S rRNA gene sequencing, with targeted urine NMR metabolites measures from 951 participants of the Study of Health in Pomerania (SHIP). We detected significant genus–metabolite associations for hippurate, succinate, indoxyl sulfate, and formate. Moreover, while replicating the previously reported association between hippurate and measures of alpha diversity, we identified formate and 4-hydroxyphenylacetate as novel markers of gut microbiome alpha diversity. Next, we predicted the urinary concentrations of each metabolite using genus abundances via an elastic net regression methodology. We found profound associations of the microbiome-based hippurate prediction score with markers of liver injury, inflammation, and metabolic health. Moreover, the microbiome-based prediction score for hippurate completely mediated the clinical association pattern of microbial diversity, hinting at a role of benzoate metabolism underlying the positive associations between high alpha diversity and healthy states. In conclusion, large-scale NMR urine metabolomics delivered novel insights into metabolic host–microbiome interactions, identifying pathways of benzoate metabolism as relevant candidates mediating the beneficial health effects of high microbial alpha diversity.

Fecal Implants From App NL-G-F and App NL-G-F/E4 Donor Mice Sufficient to Induce Behavioral Phenotypes in Germ-Free Mice.

The gut microbiome and the gut brain axis are potential determinants of Alzheimer’s disease (AD) etiology or severity and gut microbiota might coordinate with the gut-brain axis to regulate behavioral phenotypes in AD mouse models. Using 6-month-old human amyloid precursor protein (hAPP) knock-in (KI) mice, which contain the Swedish and Iberian mutations [APP NL-F (AppNL–F)] or the Arctic mutation as third mutation [APP NL-G-F (AppNL–G–F)], behavioral and cognitive performance is associated with the gut microbiome and APP genotype modulates this association. In this study, we determined the feasibility of behavioral testing of mice in a biosafety cabinet and whether stool from 6-month-old AppNL–G–F mice or AppNL–G–F crossed with human apoE4 targeted replacement mice is sufficient to induce behavioral phenotypes in 4-5 month-old germ-free C57BL/6J mice 4 weeks following inoculation. We also compared the behavioral phenotypes of the recipient mice with that of the donor mice. Finally, we assessed cortical Aβ levels and analyzed the gut microbiome in the recipient mice. These results show that it is feasible to behaviorally test germ-free mice inside a biosafety cabinet. However, the host genotype was critical in modulating the pattern of induced behavioral phenotypes as compared to those seen in the genotype- and sex-match donor mice. Male mice that received stool from AppNL–G–F and AppNL–G–F/E4 donor genotypes tended to have lower body weight as compared to wild type, an effect not observed among donor mice. Additionally, AppNL–G–F/E4 recipient males, but not females, showed impaired object recognition. Insoluble Aβ40 levels were detected in AppNL–G–F and AppNL–G–F/E4 recipient mice. Recipients of AppNL–G–F, but not AppNL–G–F/E4, donor mice carried cortical insoluble Aβ40 levels that positively correlated with activity levels on the first and second day of open field testing. For recipient mice, the interaction between donor genotype and several behavioral scores predicted gut microbiome alpha-diversity. Similarly, two behavioral performance scores predicted microbiome composition in recipient mice, but this association was dependent on the donor genotype. These data suggest that genotypes of the donor and recipient might need to be considered for developing novel therapeutic strategies targeting the gut microbiome in AD and other neurodegenerative disorders.

A posteriori dietary patterns better explain variations of the gut microbiome than individual markers in the American Gut Project

ABSTRACTBackgroundIndividual diet components and specific dietary regimens have been shown to impact the gut microbiome.ObjectivesHere, we explored the contribution of long-term diet by searching for dietary patterns that would best associate with the gut microbiome in a population-based cohort.MethodsUsing a priori and a posteriori approaches, we constructed dietary patterns from an FFQ completed by 1800 adults in the American Gut Project. Dietary patterns were defined as groups of participants or combinations of food variables (factors) driven by criteria ranging from individual nutrients to overall diet. We associated these patterns with 16S ribosomal RNA–based gut microbiome data for a subset of 744 participants.ResultsCompared to individual features (e.g., fiber and protein), or to factors representing a reduced number of dietary features, 5 a posteriori dietary patterns based on food groups were best associated with gut microbiome beta diversity (P ≤ 0.0002). Two patterns followed Prudent-like diets—Plant-Based and Flexitarian—and exhibited the highest Healthy Eating Index 2010 (HEI-2010) scores. Two other patterns presented Western-like diets with a gradient in HEI-2010 scores. A fifth pattern consisted mostly of participants following an Exclusion diet (e.g., low carbohydrate). Notably, gut microbiome alpha diversity was significantly lower in the most Western pattern compared to the Flexitarian pattern (P ≤ 0.009), and the Exclusion diet pattern was associated with low relative abundance of Bifidobacterium (P ≤ 1.2 × 10–7), which was better explained by diet than health status.ConclusionsWe demonstrated that global-diet a posteriori patterns were more associated with gut microbiome variations than individual dietary features among adults in the United States. These results confirm that evaluating diet as a whole is important when studying the gut microbiome. It will also facilitate the design of more personalized dietary strategies in general populations.