scholarly journals MON-022 Dissecting the Interplay Between Diet and PCOS Pathology on Gut Microbiota in a PCOS Mouse Model

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Valentina Rodriguez Paris ◽  
Nadeem O Kaakoush ◽  
Samantha M Solon-Biet ◽  
Melissa C Edwards ◽  
William L Ledger ◽  
...  

Abstract The gut microbiome has been implicated in the development of metabolic disorders such as obesity and type-2 diabetes, and more recently polycystic ovary syndrome (PCOS). PCOS is a heterogeneous disorder with reproductive, endocrine and metabolic irregularities, and clinical and animal studies have reported that PCOS causes a decrease in microbial diversity and composition. Diet is an important regulator of the gut microbiome, and a recent study identified that alterations in macronutrient balance impact gut microbial communities which correlate with different metabolic health outcomes (1). We have identified that macronutrient balance impacts the development of PCOS traits. Therefore, to investigate the interplay between macronutrient balance and a PCOS environment on the gut microbiome, we analyzed the intestinal microbiome from fecal pellets of control and DHT-induced PCOS mice exposed to 10 different diets that varied systematically in protein (P), carbohydrate (C) and fat (F) content. The amount of dietary P, C and F consumed significantly altered alpha and beta diversity of the gut microbiota of pooled control and PCOS mice (P<0.0001). Alpha diversity between control and PCOS mice on the same diet did not differ significantly, and hence was only affected by diet composition. However, beta diversity was significantly altered between control and PCOS mice (P<0.05). We performed DESeq2 analysis and identified an operational taxonomic unit (OTU) within Bacteroides (OTU3) to be the most differentially abundant OTU between control and PCOS mice, with a significant decrease in PCOS mice compared to controls (control: 7.88 and PCOS: 5.38; fold change = 1.464; P<0.0001). The consensus sequence of Bacteroides OTU3 was found to share 99.2% similarity to Bacteroides acidifaciens. B. acidifaciens is associated with obesity with elevated levels reported to prevent the onset of obesity (2). Thus, we then investigated the influence of P, C and F on the relative abundance of Bacteroides OTU3 and revealed an association with C consumption, with increasing levels of C leading to increased levels of Bacteroides OTU3 (Carb: r= 0.22, p=0.0028, q=0.015). These findings demonstrate that diet exerts a stronger influence over the gut microbiome than PCOS pathology. However, the hyperandrogenic PCOS environment does lead to changes in gut microbiota beta diversity, with a specific decrease in an obesity-associated (2) Bacteroides species in PCOS mice that is also responsive to levels of C consumption. Reference: (1) Holmes et al., Cell Metabolism. 2017; 25(1): 140-151. (2) Yang et al., Mucosal Immunology. 2017, 10 (1), 104-116.

Pathogens ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 463
Author(s):  
Mariusz Sikora ◽  
Albert Stec ◽  
Magdalena Chrabaszcz ◽  
Aleksandra Knot ◽  
Anna Waskiel-Burnat ◽  
...  

(1) Background: A growing body of evidence highlights that intestinal dysbiosis is associated with the development of psoriasis. The gut–skin axis is the novel concept of the interaction between skin diseases and microbiome through inflammatory mediators, metabolites and the intestinal barrier. The objective of this study was to synthesize current data on the gut microbial composition in psoriasis. (2) Methods: We conducted a systematic review of studies investigating intestinal microbiome in psoriasis, using the PRISMA checklist. We searched MEDLINE, EMBASE, and Web of Science databases for relevant published articles (2000–2020). (3) Results: All of the 10 retrieved studies reported alterations in the gut microbiome in patients with psoriasis. Eight studies assessed alpha- and beta-diversity. Four of them reported a lack of change in alpha-diversity, but all confirmed significant changes in beta-diversity. At the phylum-level, at least two or more studies reported a lower relative abundance of Bacteroidetes, and higher Firmicutes in psoriasis patients versus healthy controls. (4) Conclusions: There is a significant association between alterations in gut microbial composition and psoriasis; however, there is high heterogeneity between studies. More unified methodological standards in large-scale studies are needed to understand microbiota’s contribution to psoriasis pathogenesis and its modulation as a potential therapeutic strategy.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sandra A. Appiah ◽  
Christine L. Foxx ◽  
Dominik Langgartner ◽  
Annette Palmer ◽  
Cristian A. Zambrano ◽  
...  

AbstractSevere injuries are frequently accompanied by hemorrhagic shock and harbor an increased risk for complications. Local or systemic inflammation after trauma/hemorrhage may lead to a leaky intestinal epithelial barrier and subsequent translocation of gut microbiota, potentially worsening outcomes. To evaluate the extent with which trauma affects the gut microbiota composition, we performed a post hoc analysis of a murine model of polytrauma and hemorrhage. Four hours after injury, organs and plasma samples were collected, and the diversity and composition of the cecal microbiome were evaluated using 16S rRNA gene sequencing. Although cecal microbial alpha diversity and microbial community composition were not found to be different between experimental groups, norepinephrine support in shock animals resulted in increased alpha diversity, as indicated by higher numbers of distinct microbial features. We observed that the concentrations of proinflammatory mediators in plasma and intestinal tissue were associated with measures of microbial alpha and beta diversity and the presence of specific microbial drivers of inflammation, suggesting that the composition of the gut microbiome at the time of trauma, or shortly after trauma exposure, may play an important role in determining physiological outcomes. In conclusion, we found associations between measures of gut microbial alpha and beta diversity and the severity of systemic and local gut inflammation. Furthermore, our data suggest that four hours following injury is too early for development of global changes in the alpha diversity or community composition of the intestinal microbiome. Future investigations with increased temporal-spatial resolution are needed in order to fully elucidate the effects of trauma and shock on the gut microbiome, biological signatures of inflammation, and proximal and distal outcomes.


2020 ◽  
Vol 16 (11) ◽  
pp. 20200430
Author(s):  
Morgan C. Slevin ◽  
Jennifer L. Houtz ◽  
David J. Bradshaw ◽  
Rindy C. Anderson

Recent research in mammals supports a link between cognitive ability and the gut microbiome, but little is known about this relationship in other taxa. In a captive population of 38 zebra finches ( Taeniopygia guttata ), we quantified performance on cognitive tasks measuring learning and memory. We sampled the gut microbiome via cloacal swab and quantified bacterial alpha and beta diversity. Performance on cognitive tasks related to beta diversity but not alpha diversity. We then identified differentially abundant genera influential in the beta diversity differences among cognitive performance categories. Though correlational, this study provides some of the first evidence of an avian microbiota–gut–brain axis, building foundations for future microbiome research in wild populations and during host development.


2020 ◽  
Vol 7 (6) ◽  
pp. e896
Author(s):  
Alexandre Lecomte ◽  
Lucie Barateau ◽  
Pedro Pereira ◽  
Lars Paulin ◽  
Petri Auvinen ◽  
...  

ObjectiveTo test the hypothesis that narcolepsy type 1 (NT1) is related to the gut microbiota, we compared the microbiota bacterial communities of patients with NT1 and control subjects.MethodsThirty-five patients with NT1 (51.43% women, mean age 38.29 ± 19.98 years) and 41 controls (57.14% women, mean age 36.14 ± 12.68 years) were included. Stool samples were collected, and the fecal microbiota bacterial communities were compared between patients and controls using the well-standardized 16S rRNA gene amplicon sequencing approach. We studied alpha and beta diversity and differential abundance analysis between patients and controls, and between subgroups of patients with NT1.ResultsWe found no between-group differences for alpha diversity, but we discovered in NT1 a link with NT1 disease duration. We highlighted differences in the global bacterial community structure as assessed by beta diversity metrics even after adjustments for potential confounders as body mass index (BMI), often increased in NT1. Our results revealed differential abundance of several operational taxonomic units within Bacteroidetes, Bacteroides, and Flavonifractor between patients and controls, but not after adjusting for BMI.ConclusionWe provide evidence of gut microbial community structure alterations in NT1. However, further larger and longitudinal multiomics studies are required to replicate and elucidate the relationship between the gut microbiota, immunity dysregulation and NT1.


2020 ◽  
pp. 089033442095757
Author(s):  
Kameron Y. Sugino ◽  
Tengfei Ma ◽  
Jean M. Kerver ◽  
Nigel Paneth ◽  
Sarah S. Comstock

Background Maternal pre-pregnancy obesity and human milk feeding have been associated with altered infant gut microbiota. Research aim Determine the relationships between maternal pre-pregnancy BMI, human milk exposure, and their influence on the infant microbiota simultaneously. Methods This was a cross-sectional study of infants at 6 months of age ( N = 36), a time when many infants are fed a mixed diet of human milk and other foods. Fecal samples and participant information were collected from a subset of dyads enrolled in two related prospective cohorts (ARCHGUT and BABYGUT) in Michigan. Sequencing the V4 region of the 16S gene was used to analyze fecal bacterial samples collected from 6-month-old infants. Participants were grouped into four categories designated by their extent of human milk exposure (100%, 80%, 50%–80%, ≤ 20% human milk in the infant diet) and by maternal pre-pregnancy BMI category (normal, overweight, obese). Results Fewer participants with pre-pregnancy obesity were breastfeeding at 6 months postpartum compared to non-obese participants (35.7% and 81.8%, respectively). In univariate analyses, maternal pre-pregnancy BMI and human milk exposure were both significantly associated with alpha and beta diversity of the infant microbiota. However, in multivariate analyses, human milk exposure accounted for 20% of the variation in alpha diversity, but pre-pregnancy BMI was not significantly associated with any form of microbiota diversity. Conclusions The proportion of the infant diet that was human milk at 6 months was the major determinant of alpha and beta diversity of the infant. Maternal obesity contributes to the gut microbiota by its association with the extent of human milk feeding.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9003
Author(s):  
Zhongwei Yin ◽  
Keping Sun ◽  
Aoqiang Li ◽  
Deyi Sun ◽  
Zhongle Li ◽  
...  

Background The gut microbiota is closely linked to host development, diet and health and is influenced by both the host and the environment. Although many studies have focused on the dynamics of the gut microbiota during development in captive animals, few studies have focused on the dynamics of the gut microbiota during development in wild animals, especially for the order Chiroptera. Methods In this study, we characterized the gut microbiota of the wild Asian particolored bat (Vespertilio sinensis) from 1 day to 6 weeks after birth. We explored the changes in their gut microbial community compositions, examined possible influencing factors, and predicted the feeding transition period. Results The gut microbiota changed during the development of V. sinensis. The alpha diversity of the bats’ gut microbiota gradually increased but did not change significantly from the 1st day to the 4th week after birth; however, the alpha diversity decreased significantly in week 5, then stabilized. The beta diversity differed slightly in weeks 4–6. In week 4, the fecal samples showed the highest diversity in bacterial community composition. Thus, we predicted that the potential feeding transition period for V. sinensis may occur during week 4. Redundancy analysis showed that age and body mass index significantly affected the compositional changes of the gut microbiota in Asian particolored bats. Conclusion The gut microbiota changed during the development of V. sinensis. We suggest that changes in the alpha and beta diversity during week 4 after birth indicate a potential feeding transition, highlighting the importance of diet in the gut microbiota during the development of V. sinensis.


2021 ◽  
Author(s):  
Jialiang Li ◽  
Xueyan Li ◽  
Sina Zhang ◽  
Chen Jin ◽  
Zixia Lin ◽  
...  

Abstract BACKGROUNDThe liver-microbiome axis is implicated in the pathogenesis of hepatobiliary cancer, and the role of the gut microbiota in cholangiocarcinoma (CCA) remains unclear.METHODWe conducted a case-control study on the intestinal flora of 33 CCA patients and 47 cholelithiasis individuals. We performed 16S rRNA gene sequencing to identify disease-related gut microbiota and assess the potential of the intestinal microbiome as a non-invasive biomarker for CCA.RESULTWe found that gut microbiome of CCA patients had a significantly higher alpha diversity (Shannon and Observed species indices, p = 0.006 and p = 0.02, respectively) and an overall different microbial community composition (p = 0.032). The genus Muribaculaceae_unclassified was most strongly associated with CCA (p < 0.001). We put forward a disease predictive model including twelve intestinal microbiome genera distinguished CCA patients from CF patients with an area under curve (AUC) of approximately 0.93 (95%CI, 0.85–0.987). The forecasting performance of this model was better than CA19-9. Moreover, genera Ezakiella and Garciella were only observed among intrahepatic cholangiocarcinoma patients. Further, we assessed predicted functional modules alternations CCA patients and uncovered a microbiota pattern specific to CCA.CONCLUSIONOur findings provide evidence of the intestinal microbiome as a non-invasive biomarker for CCA.


2021 ◽  
Author(s):  
Laurel E. Redding ◽  
Alexander S. Berry ◽  
Nagaraju Indugu ◽  
Elizabeth Huang ◽  
Daniel P. Beiting ◽  
...  

Diarrheal disease, a major cause of morbidity and mortality in dairy calves, is strongly associated with the health and composition of the gut microbiome. Clostridioides difficile is an opportunistic pathogen that proliferates and can produce enterotoxins when the host experiences gut dysbiosis. However, even asymptomatic colonization with C. difficile can be associated with differing degrees of microbiome disruption in a range of species, including people, swine, and dogs. Little is known about the interaction between C. difficile and the gut microbiome in dairy calves. In this study, we sought to define microbial features associated with C. difficile colonization in pre-weaned dairy calves less than 2 weeks of age. We characterized the fecal microbiota of 80 calves from 23 different farms using 16S rRNA sequencing and compared the microbiota of C. difficile -positive (n=24) and C. difficile -negative calves (n=56). Farm appeared to be the greatest source of variability in the gut microbiota. When controlling for calf age, diet, and farm location, there was no significant difference in Shannon alpha diversity ( P = 0.50) or in weighted UniFrac beta diversity (P=0.19) between C. difficile -positive and –negative calves. However, there was a significant difference in beta diversity as assessed using Bray-Curtiss diversity ( P =0.0077), and C. difficile -positive calves had significantly increased levels of Ruminococcus (gnavus group) ( Adj. P =0.052), Lachnoclostridium ( Adj. P =0.060), Butyricicoccus ( Adj. P =0.060), and Clostridium sensu stricto 2 compared to C. difficile -negative calves. Additionally, C. difficile -positive calves had fewer microbial co-occurrences than C. difficile –negative calves, indicating reduced bacterial synergies. Thus, while C. difficile colonization alone is not associated with dysbiosis and is therefore unlikely to result in an increased likelihood of diarrhea in dairy calves, it may be associated with a more disrupted microbiota.


2021 ◽  
Vol 14 (9) ◽  
pp. 931
Author(s):  
Bahtiyar Yilmaz ◽  
Lisa Ruckstuhl ◽  
Beat Müllhaupt ◽  
Lorenzo Magenta ◽  
Melanie Harrer Kuster ◽  
...  

In this small pilot sub-study, longitudinal gut microbiota composition changes, after successful treatment of hepatitis C virus (HCV) with the co-formulated glecaprevir/pibrentasvir (GLE/PIB), were analyzed before treatment (baseline) and 12 weeks post-treatment. Participating patients provided a fresh stool sample the week before their study visit, from which microbial DNA was extracted and sequenced for the 16S rRNA region in an Illumina MiSeq2 platform. Microbial and statistical analyses were conducted to determine the alpha-diversity (number of different taxa within a sample) and beta-diversity (number of overlapping taxa between samples). Stool samples from 58 patients were eligible for analysis. There were 27 patients with HCV genotype 1, 10 with genotype 2, 16 with genotype 3, and 5 with genotype 4. No statistically significant differences in gut microbiota diversity, species richness, or microbial community pattern were found at baseline and at post-treatment Week 12. Lack of statistically significant differences remained consistent in further analysis by demographic and baseline disease characteristics. Surprisingly, no statistically significant changes in alpha- and beta-diversity were seen in the microbiota after GLE/PIB treatment, though there was a trend toward less richness over time. Further investigation is needed into this unexpected outcome to better understand the role of HCV treatment and the gut microbiota.


Author(s):  
Maciej Chichlowski ◽  
Nicholas Bokulich ◽  
Cheryl L Harris ◽  
Jennifer L Wampler ◽  
Fei Li ◽  
...  

Abstract Background Milk fat globule membrane (MFGM) and lactoferrin (LF) are human milk bioactive components demonstrated to support gastrointestinal (GI) and immune development. Significantly fewer diarrhea and respiratory-associated adverse events through 18 months of age were previously reported in healthy term infants fed a cow's milk-based infant formula with added source of bovine MFGM and bovine LF through 12 months of age. Objectives To compare microbiota and metabolite profiles in a subset of study participants. Methods Stool samples were collected at Baseline (10–14 days of age) and Day 120 (MFGM + LF: 26, Control: 33). Bacterial community profiling was performed via16S rRNA gene sequencing (Illumina MiSeq) and alpha and beta diversity were analyzed (QIIME 2). Differentially abundant taxa were determined using Linear discriminant analysis effect size (LefSE) and visualized (Metacoder). Untargeted stool metabolites were analyzed (HPLC/mass spectroscopy) and expressed as the fold-change between group means (Control: MFGM + LF ratio). Results Alpha diversity increased significantly in both groups from baseline to 4 months. Subtle group differences in beta diversity were demonstrated at 4 months (Jaccard distance; R2 = 0.01, P = 0.042). Specifically, Bacteroides uniformis and Bacteroides plebeius were more abundant in the MFGM + LF group at 4 months. Metabolite profile differences for MFGM + LF vs Control included: lower fecal medium chain fatty acids, deoxycarnitine, and glycochenodeoxycholate, and some higher fecal carbohydrates and steroids (P &lt; 0.05). After applying multiple test correction, the differences in stool metabolomics were not significant. Conclusions Addition of bovine MFGM and LF in infant formula was associated with subtle differences in stool microbiome and metabolome by four months of age, including increased prevalence of Bacteroides species. Stool metabolite profiles may be consistent with altered microbial metabolism. Trial registration:  https://clinicaltrials.gov/ct2/show/NCT02274883).


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