Higher Abundance Of Prevotella Research Articles

Progression of swine fecal microbiota during early stages of life and its association with performance: a longitudinal study

BackgroundIt is vital to understand healthy gut microbiota composition throughout early life stages when environments are changing, and immunity is developing. There are limited large-scale longitudinal studies classifying healthy succession of swine microbiota. The objectives of this study were to (a) determine the microbiota composition of fecal samples collected from piglets within a few days after birth until one-week post-weaning, and (b) investigate the associations of early fecal microbiota with pig growth performance in nursery and later growing stages. Fecal samples were collected from nine cohorts of 40 pigs (n = 360) from distinct farrowing sources in Ontario and Quebec, Canada at four timepoints from birth to one-week post-weaning, with pig body weight was recorded at each fecal sampling.ResultsMicrobiota was dominated by the phyla Firmicutes, Bacteroides and Proteobacteria. There were notable differences in genera abundance between pigs from different provinces and farming systems. Over the early life stage, the genera Bacteroides, Escherichia/Shigella, and Clostridium cluster XIVa were abundant preweaning, while Prevotella dominated post-weaning. Hierarchical clustering identified three major stages of microbiota development, each associated with distinct composition. Stage one occurs from birth to 7 days, stage two from 7 days after birth until weaning, and stage three from weaning to one-week post-weaning. Three enterotypes were identified in stage two that showed differences in growth before weaning, and in the grower production stage. Piglets with a microbiota enterotype characterized by higher abundance of Prevotella and unclassified Ruminococcaceae had lower growth performance in the pre-weaning stage, and the growing stage.ConclusionThese findings help identify the timing of microbiota shifts across early swine life which may be the optimal time for external intervention to shift the microbiota to a beneficial state. The project findings should help decrease antimicrobial use, increase animal welfare, and have positive economic impacts.

Prevotella enterotype associates with diets supporting acidic faecal pH and production of propionic acid by microbiota

Metabolism of dietary fibres by colon microbiota plays an important role for human health. Personal data from a nutrition study (57 subjects) were analysed to elucidate quantitative associations between the diet, faecal microbiome, organic acid concentrations and pH. Ratios of the predominant acids acetate, butyrate and propionate ranged from 1:0.67:0.27 to 1:0.17:0.36. Pectin-rich diets resulted in higher faecal acetate concentrations. Negative correlation between faecal pH and BSS was observed. Higher faecal pH and lower acid concentrations were related to the higher abundance of amino acid degrading Clostridium, Odoribacter and Eubacterium coprostanoligenes, which are weak carbohydrate fermenting taxa. Propionic acid correlated especially to high abundance of Prevotella and low abundance of proteobacteria. The acetate to propionate ratio of the Prevotella enterotype was about half of that of the Bacteroides enterotype. Based on the results we suggest the measurement of faecal pH and organic acid composition for research and diagnostic purposes.

Effect of Lactobacillaceae Probiotics on Colonic Microbiota and Metabolite Production in Cystic Fibrosis: A Comparative In Vitro Study.

Cystic Fibrosis-related gut dysbiosis (CFRGD) has become a recognised complication in children with this condition, and current evidence remains insufficient to guide the selection of probiotic strains for supplementation treatments. The aim of this study was to characterise the effect of three probiotic strains on CFRGD by means of a dynamic in vitro simulation of the colonic fermentation (SHIME®). The configuration of the system included three bioreactors colonised with the faecal inoculum of a child with cystic fibrosis. For 20 days, each bioreactor was supplied daily with either Lacticaseibacillus rhamnosus GG (ATCC 53103 TM), Limosilactobacillus reuteri (DSM 17938) or Lactiplantibacillus plantarum (DSM 22266). The baseline microbiota was characterised by a high abundance of Prevotella, Faecalibacterium and Acidaminococcus genera. After 20 days of supplementation, L. rhamnosus and L. plantarum reduced Prevotella significantly, and the three strains led to increased Faecalibacterium and Bifidobacterium and decreased Acidaminococcus, with some of these changes being maintained 10 days after ceasing supplementation. The metabolic activity remained unaltered in terms of short-chain fatty acids, but branched-chain fatty acids showed a significant decrease, especially with L. plantarum. Additionally, ammonia decreased at 20 days of supplementation, and lactate continuously increased with the three strains. The effects on colonic microbiota of L. rhamnosus, L. reuteri or L. plantarum were established, including increased beneficial bacteria, such as Faecalibacterium, and beneficial metabolites such as lactate; and on the other hand, a reduction in pathogenic genera, including Prevotella or Acidaminococcus and branched-chain fatty acids, overall supported their use as probiotics in the context of CFRGD.

Heating Drinking Water in Cold Season Improves Growth Performance via Enhancing Antioxidant Capacity and Rumen Fermentation Function of Beef Cattle.

The research aimed to investigate the suitable drinking water temperature in winter and its effect on the growth performance, antioxidant capacity, and rumen fermentation function of beef cattle. A total of 40 beef cattle (640 ± 19.2 kg) were randomly divided into five treatments with eight cattle in each treatment raised in one pen according to initial body weight. Each treatment differed only in the temperature of drinking water, including the room-temperature water and four different heat water groups named RTW, HW_1, HW_2, HW_3, and HW_4. The measured water temperatures were 4.39 ± 2.546 °C, 10.6 ± 1.29 °C, 18.6 ± 1.52 °C, 26.3 ± 1.70 °C, and 32.5 ± 2.62 °C, respectively. The average daily gain (ADG) showed a significant linear increase during d 0 to 60 and a quadratic increase during d 31 to 60 with rising water temperature (p < 0.05), and the highest ADG of 1.1911 kg/d was calculated at a water temperature of 23.98 °C (R2 = 0.898). The average rectal temperature on d 30 (p = 0.01) and neutral detergent fiber digestibility (p < 0.01) increased linearly with increasing water temperature. Additionally, HW_2 reduced serum triiodothyronine, thyroxine, and malondialdehyde (p < 0.05), and increased serum total antioxidant capacity (p < 0.05) compared with RTW. Compared with HW_2, RTW had unfavorable effects on ruminal propionate, total volatile fatty acids, and cellulase concentrations (p < 0.05), and lower relative mRNA expression levels of claudin-4 (p < 0.01), occludin (p = 0.02), and zonula occludens-1 (p = 0.01) in the ruminal epithelium. Furthermore, RTW had a higher abundance of Prevotella (p = 0.04), Succinivibrionaceae_UCG-002 (p = 0.03), and Lachnospiraceae_UCG-004 (p = 0.03), and a lower abundance of Bifidobacteriaceae (p < 0.01) and Marinilabiliaceae (p = 0.05) in rumen compared to HW_2. Taken together, heated drinking water in cold climates could positively impact the growth performance, nutrient digestibility, antioxidant capacity, and rumen fermentation function of beef cattle. The optimal water temperature for maximizing ADG was calculated to be 23.98 °C under our conditions. Ruminal propionate and its producing bacteria including Prevotella, Succinivibrionaceae, and Lachnospiraceae might be important regulators of rumen fermentation of beef cattle drinking RTW under cold conditions.

Milk protein digestion and the gut microbiome influence gastrointestinal discomfort after cow milk consumption in healthy subjects

Many healthy people suffer from milk-related gastrointestinal discomfort (GID) despite not being lactose intolerant; the mechanisms underpinning such condition are unknown.This study aimed to explore milk protein digestion and related physiological responses (primary outcome), gut microbiome and gut permeability in 19 lactose-tolerant healthy nonhabitual milk consumers [NHMCs] reporting GID after consuming cow milk compared to 20 habitual milk consumers [HMCs] without GID.NHMCs and HMCs participated in a milk-load (250 mL) test, underwent blood sample collection at 6 time points over 6 h after milk consumption and collected urine samples and GID self-reports over 24 h. We measured the concentrations of 31 milk-derived bioactive peptides (BAPs), 20 amino acids, 4 hormones, 5 endocannabinoid system mediators, glucose and the dipeptidyl peptidase-IV (DPPIV) activity in blood and indoxyl sulfate in urine samples. Subjects also participated in a gut permeability test and delivered feces sample for gut microbiome analysis.Results showed that, compared to HMCs, milk consumption in NHMCs, along with GID, elicited a slower and lower increase in circulating BAPs, lower responses of ghrelin, insulin, and anandamide, a higher glucose response and serum DPPIV activity. The gut permeability of the two groups was similar, while the habitual diet, which was lower in dairy products and higher in the dietary-fibre-to-protein ratio in NHMCs, possibly shaped the gut microbiome; NHMCs exhibited lower abundance of Bifidobacteria, higher abundance of Prevotella and lower abundance of protease-coding genes, which may have reduced protein digestion, as evidenced by lower urinary excretion of indoxyl sulfate.In conclusion, the findings showed that a less efficient digestion of milk proteins, supported by a lower proteolytic capability of the gut microbiome, may explain GID in healthy people after milk consumption.

Could Gut Microbiota Composition Be a Useful Indicator of a Long-Term Dietary Pattern?

Despite the known effects of diet on gut microbiota composition, not many studies have evaluated the relationship between distinct dietary patterns and gut microbiota. The aim of our study was to determine whether gut microbiota composition could be a useful indicator of a long-term dietary pattern. We collected data from 89 subjects adhering to omnivorous, vegetarian, vegan, and low-carbohydrate, high-fat diet that were equally distributed between groups and homogenous by age, gender, and BMI. Gut microbiota composition was analyzed with a metabarcoding approach using V4 hypervariable region of the 16S rRNA gene. K-means clustering of gut microbiota at the genus level was performed and the nearest neighbor classifier was applied to predict microbiota clustering classes. Our results suggest that gut microbiota composition at the genus level is not a useful indicator of a subject’s dietary pattern, with the exception of a vegan diet that is represented by a high abundance of Prevotella 9. Based on our model, a combination of 26 variables (anthropometric measurements, serum biomarkers, lifestyle factors, gastrointestinal symptoms, psychological factors, specific nutrients intake) is more important to predict an individual’s microbiota composition cluster, with 91% accuracy, than the dietary intake alone. Our findings could serve to develop strategies to educate individuals about changes of some modifiable lifestyle factors, aiming to classify them into clusters with favorable health markers, independent of their dietary pattern.

Assessment of cecal microbiota modulation from piglet dietary supplementation with copper

BackgroundSwine production expanded in the last decades. Efforts have been made to improve meat production and to understand its relationship to pig gut microbiota. Copper (Cu) is a usual supplement to growth performance in animal production. Here, two performance studies were conducted to investigate the effects of three different sources of Cu on the microbiota of piglets. A total of 256 weaned piglets were randomly allocated into 4 treatments (10 replicates per treatment of 4 piglets per pen in Trial 1 and 8 replicates of 3 piglets per pen in Trial 2). Treatments included a control group (fed 10 mg/kg of Cu from CuSO4), a group fed at 160 mg/kg of Copper (II) sulfate (CuSO4) or tri-basic copper chloride (TBCC), and a group fed with Cu methionine hydroxy analogue chelated (Cu-MHAC) at 150, 80, and 50 mg/kg in Phases 1 (24–35 d), 2 (36–49 d), and 3 (50–70 d), respectively. At 70 d, the cecum luminal contents from one pig per pen were collected and polled for 16 S rRNA sequencing (V3/V4 regions). Parameters were analyzed in a completely randomized block design, in which each experiment was considered as a block.ResultsA total of 1337 Operational Taxonomic Units (OTUs) were identified. Dominance and Simpson ecological metrics were statistically different between control and treated groups (P < 0.10) showing that different Cu sources altered the gut microbiota composition with the proliferation of some bacteria that improve gut health. A high abundance of Prevotella was observed in all treatments while other genera were enriched and differentially modulated, according to the Cu source and dosage. The supplementation with Cu-MHAC can modify a group of bacteria involved in feed efficiency (FE) and short chain fatty acids (SCFA) production (Clostridium XIVa, Desulfovibrio, and Megasphera). These bacteria are also important players in the activation of ghrelin and growth hormones that were previously reported to correlate with Cu-MHAC supplementation.ConclusionsThese results indicated that some genera seem to be directly affected by the Cu source offered to the animals. TBCC and Cu-MHAC (even in low doses) can promote healthy modifications in the gut bacterial composition, being a promising source of supplementation for piglets.

Correlation between the intestinal microflora and peripheral blood Th1/Th2 balance in hypothyroidism during the first half of pregnancy.

This study aimed to investigate the relationship between intestinal microflora characteristics and the peripheral blood T helper cell (Th)1/Th2 balance in patients with hypothyroidism during the first half of pregnancy. The Th1/Th2 ratios in the peripheral blood of pregnant women in the hypothyroidism and control groups were determined using flow cytometry. The cytometric bead array assay was used to determine the serum levels of interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ. Moreover, 16S rRNA amplicon sequencing was used to determine the intestinal microbial composition in the two groups. Finally, the relationships between intestinal microflora, Th1/Th2 cells, cytokines, and clinical indicators were analyzed. C-reactive protein levels were higher in the hypothyroidism group than in the control group. In contrast to the control group, the hypothyroidism group showed an increase in Th1 cells and the Th1/Th2 ratio, and a decrease in Th2 cells. The hypothyroidism group had higher serum IL-2, TNF-α, and IFN-γ levels, and lower IL-10 levels, than the control group. The richness of the intestinal microflora in the hypothyroidism group increased whereas the diversity decreased. The linear discriminant analysis effect size revealed that the hypothyroidism group had a higher abundance of Prevotella and Faecalibacterium, but a lower abundance of Bacteroides, compared to the control group. Prevotella was positively correlated with Th1 cells, the Th1/2 ratio, and TNF-α. Bacteroides was positively correlated with Th2 cells and IL-10, but negatively correlated with Th1 cells, the Th1/2 ratio, TNF-α, and IFN-γ. The thyroid peroxidase antibody level was directly proportional to TNF-α. A Th1/Th2 imbalance occurs in patients with hypothyroidism during the first half of pregnancy. Disorders of the intestinal microflora may lead to hypothyroidism during pregnancy by affecting the Th1/Th2 balance.

An Exploratory Case-Control Study on the Associations of Bacterially-Derived Vitamin K Forms with the Intestinal Microbiome and Obesity-Related Osteoarthritis

BackgroundEvidence suggests that natural metabolites produced by intestinal microorganisms may have beneficial or harmful effects on osteoarthritis (OA). This could include menaquinones, which are bacterially-synthesized, biologically-active vitamin K forms abundant in the intestinal microbiome. ObjectivesThe overall goal of this study was to evaluate the association of intestinally-derived menaquinones with obesity-related OA. MethodsThis case-control study used data and biospecimens derived from a subgroup of Johnston County Osteoarthritis Study participants. Fecal menaquinone concentrations and microbial composition were determined in 52 obese participants with hand and knee OA and 42 age- and sex-matched obese participants without OA. The inter-relationships among fecal menaquinones were evaluated using principal component analysis. The differences in alpha and beta diversities and microbial composition across menaquinone clusters were evaluated using ANOVA. ResultsThe samples were clustered into the following 3 groups: cluster 1 characterized by higher fecal menaquinone-9 and -10 concentrations, cluster 2 characterized by lower overall menaquinone concentrations, and cluster 3 characterized by higher menaquinone-12 and -13 concentrations. Overall, fecal menaquinone clusters did not differ between participants with or without OA (P = 0.707). Microbial diversity did not differ across the fecal menaquinone clusters (all F-test P > 0.12). However, the relative abundance of bacterial taxa differed among clusters, with higher abundance of Coprococcus, Prevotella, and Eggerthella in cluster 2 than in cluster 1; higher abundance of Oscillospira, Dorea, Eubacterium, and Bacteroides in cluster 3 than in cluster 1; and higher abundance of Prevotella, Sutterella, and Dorea in cluster 3 than in cluster 2 (all P < 0.001). ConclusionMenaquinones were variable and abundant in the human gut, but the fecal menaquinone clusters did not differ with OA status. Although the relative abundance of specific bacterial taxa differed among fecal menaquinone clusters, the relevance of these differences with respect to vitamin K status and human health is uncertain.

Impact of Visceral Obesity on Structural and Functional Alterations of Gut Microbiota in Polycystic Ovary Syndrome (PCOS): A Pilot Study Using Metagenomic Analysis.

We aimed to identify structural and functional alterations of gut microbiota associated with visceral obesity in adult women with polycystic ovary syndrome (PCOS). Twenty-seven adults with PCOS underwent stool and fasting blood collection, oral glucose tolerance testing, and visceral fat area (VFA) measurement via dual-bioimpedance technique. Metagenomic analysis was used to analyze gut microbiota. PCOS patients were divided into three groups: visceral obesity group (PCOS-VO, n=9, age 28.33±5.68 years, BMI 37.06±4.27 kg/m2, VFA 128.67±22.45 cm2), non-visceral obesity group (PCOS-NVO, n=10, age 25.40±4.53, BMI 30.74±3.95, VFA 52.00±24.04), normal BMI group (PCOS-NB, n=8, age 27.88±2.53, BMI 21.56±2.20, VFA 27.00±21.18), with no statistical difference in age (P>0.05) and significantly statistical differences in BMI and VFA (P<0.05). The groups showed a significant difference in microbial β-diversity between PCOS-VO and PCOS-NVO (P=0.002) and no difference between PCOS-NVO and PCOS-NB (P=0.177). Bacteroidetes was the phylum with the highest relative abundance among all patients, followed by Firmicutes. Those with visceral obesity had a higher abundance of Prevotella, Megamonas, and Dialister genera, positively correlated with metabolic markers (r>0.4, P<0.05), and lower abundance of Phascolarctobacterium and Neisseria genera, negatively correlated with metabolic markers (r<-0.4, P<0.05). Functional annotation analysis showed significant differences in relative abundance of ribosome pathway, fatty acid biosynthesis pathway, and sphingolipid signaling pathway between groups, affecting lipid homeostasis and visceral fat accumulation. Alteration in β-diversity of gut microbiota exists in PCOS with visceral obesity versus those without visceral obesity and relates to functional differences in ribosomes, fatty acid biosynthesis, and sphingolipid signaling pathways.

Enterotypical Prevotella and three novel bacterial biomarkers in preoperative stool predict the clinical outcome of colorectal cancer

BackgroundA significant proportion of colorectal cancer (CRC) patients suffer from early recurrence and progression after surgical treatment. Although the gut microbiota is considered as a key player in the initiation and progression of CRC, most prospective studies have been focused on a particular pathobionts such as Fusobacterium nucleatum. Here, we aimed to identify novel prognostic bacteria for CRC by examining the preoperative gut microbiota through 16S ribosomal RNA gene sequencing.ResultsWe collected stool samples from 333 patients with primary CRC within 2 weeks before surgery and followed up the patients for a median of 27.6 months for progression and 43.6 months for survival. The sequence and prognosis data were assessed using the log-rank test and multivariate Cox proportional hazard analysis. The gut microbiota was associated with the clinical outcomes of CRC patients (Pprogress = 0.011, Pdecease = 0.007). In particular, the high abundance of Prevotella, a representative genus of human enterotypes, indicated lower risks of CRC progression (P = 0.026) and decease (P = 0.0056), while the occurrence of Alistipes assigned to Bacteroides sp., Pyramidobacter piscolens, Dialister invisus, and Fusobacterium nucleatum indicated a high risk of progression. A microbiota-derived hazard score considering the five prognostic bacteria accurately predicted CRC progression in 1000 random subsamples; it outperformed widely accepted clinical biomarkers such as carcinoembryonic antigen and lymphatic invasion, after adjustment for the clinicopathological stage (adjusted HR 2.07 [95% CI, 1.61–2.64], P = 7.8e−9, C-index = 0.78). PICRUSt2 suggested that microbial pathways pertaining to thiamine salvage and L-histidine degradation underlie the different prognoses.ConclusionsThe enterotypical genus Prevotella was demonstrated to be useful in improving CRC prognosis, and combined with the four pathobionts, our hazard score based on the gut microbiota should provide an important asset in predicting medical outcomes for CRC patients.48KLrU1kw-NevPNeR-hyqwVideo

Oral microbiota and periodontitis severity among Hispanic adults.

Periodontitis, one of the most common bacterial infections characterized by chronic inflammation, is also known to be a risk factor for chronic conditions, including cardiovascular disease and cancer. This inflammation is driven by an altered microbiotawith an increase in pathogenic bacteria. We evaluated the association between oral microbiota and periodontitis severity in high-risk Hispanics. This cross-sectional study recruited 134 sexually active participants aged 21 to 49 years old from STI Clinics in Puerto Rico. A periodontal examination, saliva collection, and an interviewer-administered questionnaire were performed. Periodontal severity was categorized as: having no disease, mild, and moderate/severe and BOP and tooth loos was noted. Saliva samples were collected for genomic DNA extraction, downstream 16S rDNA amplification sequencing, and bioinformatics analyses. The structure, composition, and diversity of bacterial communities differed significantly according to periodontal severity. The richness and overall diversity also differed between participants without periodontitis and participants with some level of periodontal disease. A higher abundance of Prevotella, Veillonella, or Treponema was attributed to periodontal disease and Aggregatibacter to severe bleeding on probing, while Neisseria was found in higher abundance in healthy participants, decreasing its levels with drinking, smoking, and oral sex practices. Our findings indicate that dysbiosis occurs as periodontal disease progresses, and both alcohol consumption and smoking habits pose risk factors for oral dysbiosis. These results are of public health and clinical impact, as several bacteria identified could serve in the future as biomarkers for periodontitis and oral cancer risk.

Alterations in rumen microbiota via oral fiber administration during early life in dairy cows

Bacterial colonization in the rumen of pre-weaned ruminants is important for their growth and post-weaning productivity. This study evaluated the effects of oral fiber administration during the pre-weaning period on the development of rumen microbiota from pre-weaning to the first lactation period. Twenty female calves were assigned to control and treatment groups (n = 10 each). Animals in both groups were reared using a standard feeding program throughout the experiment, except for oral fiber administration (50–100 g/day/animal) from 3 days of age until weaning for the treatment group. Rumen content was collected during the pre-weaning period, growing period, and after parturition. Amplicon sequencing of the 16S rRNA gene revealed that oral fiber administration facilitated the early establishment of mature rumen microbiota, including a relatively higher abundance of Prevotella, Shuttleworthia, Mitsuokella, and Selenomonas. The difference in the rumen microbial composition between the dietary groups was observed even 21 days after parturition, with a significantly higher average milk yield in the first 30 days of lactation. Therefore, oral fiber administration to calves during the pre-weaning period altered rumen microbiota, and its effect might be long-lasting until the first parturition.

Plasma Lipid Profile and Intestinal Microflora in Pregnancy Women With Hypothyroidism and Their Correlation With Pregnancy Outcomes

ObjectiveTo investigate the lipid profiles and intestinal microflora in pregnant patients with hypothyroidism and their correlation with pregnancy outcomes.MethodsIn total, 27 pregnant women with hypothyroidism (study case) and 28 normal pregnant women (control group) were enrolled in this study. The lipid profiles and intestinal microflora in the two groups were compared using untargeted liquid chromatography-mass spectrometry (LC-MS) and 16S rRNA amplicon sequencing, respectively. The association among the differential metabolites, intestinal microflora, serological indicators and pregnancy outcomes was further analyzed.ResultsPatients in study case had higher C-reactive protein (CRP) levels (P = 0.025) and lower birth weight (P=0.005) than the control group. A total of 42 differential lipid metabolites and 7 enrichment KEGG pathways were obtained between the two groups (VIP ≥ 1, P < 0.05). Ten lipid metabolites can be used as characteristic metabolites of study case, including phosphatidylcholine (PC), phosphatidylethanolamine (PE) and sphingomyelin (SM). The richness and diversity of intestinal microflora in study case were lower than those in the control group (P>0.05). LEfSe analysis revealed that patients in study case had higher abundance of Prevotella and Haemophilus and lower abundance of Blautia than the control group (P < 0.05). Blautia was positively correlated with SM and negatively correlated with PC and PE; the CRP level and Prevotella were positively correlated; the neonatal weight and PC level were negatively correlated (P < 0.05).ConclusionThe lipid profile and intestinal microflora of pregnant women with hypothyroidism significantly differed from those of normal pregnant women and were associated with adverse pregnancy outcomes. The interaction between lipid metabolism and intestinal microflora may be a potential target for further studies investigating the pathogenesis of hypothyroidism during pregnancy.

Cannabinoid control of gingival immune activation in chronically SIV-infected rhesus macaques involves modulation of the indoleamine-2,3-dioxygenase-1 pathway and salivary microbiome.

SummaryBackgroundHIV/SIV-associated periodontal disease (gingivitis/periodontitis) (PD) represents a major comorbidity affecting people living with HIV (PLWH) on combination anti-retroviral therapy (cART). PD is characterized by chronic inflammation and dysbiosis. Nevertheless, the molecular mechanisms and use of feasible therapeutic strategies to reduce/reverse inflammation and dysbiosis remain understudied and unaddressed.MethodsEmploying a systems biology approach, we report molecular, metabolome and microbiome changes underlying PD and its modulation by phytocannabinoids [delta-9-tetrahydrocannabinol (Δ9-THC)] in uninfected and SIV-infected rhesus macaques (RMs) untreated (VEH-untreated/SIV) or treated with vehicle (VEH/SIV) or Δ9-THC (THC/SIV).FindingsVEH- untreated/SIV but not THC/SIV RMs showed significant enrichment of genes linked to anti-viral defense, interferon-β, NFκB, RIG-1, and JAK-STAT signaling. We focused on the anti-microbial DUOX1 and immune activation marker IDO1 that were reciprocally regulated in the gingiva of VEH-untreated/SIV RMs. Both proteins localized to the gingival epithelium and CD163+ macrophages, and showed differential expression in the gingiva of THC/SIV and VEH/SIV RMs. Additionally, inflammation-associated miR-21, miR-142–3p, miR-223, and miR-125a-5p showed significantly higher expression in the gingiva of VEH/SIV RMs. In human primary gingival epithelial cells, miR-125a-5p post-transcriptionally downregulated DUOX1 and THC inhibited IDO1 protein expression through a cannabinoid receptor-2 mediated mechanism. Interestingly, THC/SIV RMs showed relatively reduced plasma levels of kynurenine, kynurenate, and the neurotoxic quinolinate compared to VEH/SIV RMs at 5 months post SIV infection (MPI). Most importantly, THC blocked HIV/SIV-induced depletion of Firmicutes and Bacteroidetes, and reduced Gammaproteobacteria abundance in saliva. Reduced IDO1 protein expression was associated with significantly (p<0.05) higher abundance of Prevotella, Lactobacillus (L. salivarius, L. buchneri, L. fermentum, L. paracasei, L. rhamnosus, L. johnsonii) and Bifidobacteria and reduced abundance of the pathogenic Porphyromonas cangingivalis and Porphyromonas macacae at 5MPI.InterpretationThe data provides deeper insights into the molecular mechanisms underlying HIV/SIV-induced PD and more importantly, the anti-inflammatory and anti-dysbiotic properties of THC in the oral cavity. Overall, these translational findings suggest that phytocannabinoids may help reduce gingival/systemic inflammation, salivary dysbiosis and potentially metabolic disease/syndrome in PLWH on cART and those with no access to cART or do not suppress the virus under cART.FundingResearch reported in this publication was supported by the National Institutes of Health Award Numbers R01DA052845 (MM and SNB), R01DA050169 (MM and CO), R01DA042524 and R56DE026930 (MM), and P51OD011104 and P51OD011133. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Gut Dysbiosis and Intestinal Barrier Dysfunction: Potential Explanation for Early-Onset Colorectal Cancer.

Colorectal cancer (CRC) is a heterogeneous disease that commonly affects individuals aged more than 50 years old globally. Regular colorectal screening, which is recommended for individuals aged 50 and above, has decreased the number of cancer death toll over the years. However, CRC incidence has increased among younger population (below 50 years old). Environmental factors, such as smoking, dietary factor, urbanization, sedentary lifestyle, and obesity, may contribute to the rising trend of early-onset colorectal cancer (EOCRC) because of the lack of genetic susceptibility. Research has focused on the role of gut microbiota and its interaction with epithelial barrier genes in sporadic CRC. Population with increased consumption of grain and vegetables showed high abundance of Prevotella, which reduces the risk of CRC. Microbes, such as Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli deteriorate in the intestinal barrier, which leads to the infiltration of inflammatory mediators and chemokines. Gut dysbiosis may also occur following inflammation as clearly observed in animal model. Both gut dysbiosis pre- or post-inflammatory process may cause major alteration in the morphology and functional properties of the gut tissue and explain the pathological outcome of EOCRC. The precise mechanism of disease progression from an early stage until cancer establishment is not fully understood. We hypothesized that gut dysbiosis, which may be influenced by environmental factors, may induce changes in the genome, metabolome, and immunome that could destruct the intestinal barrier function. Also, the possible underlying inflammation may give impact microbial community leading to disruption of physical and functional role of intestinal barrier. This review explains the potential role of the interaction among host factors, gut microenvironment, and gut microbiota, which may provide an answer to EOCRC.

Vegan Diet and the Gut Microbiota Composition in Healthy Adults.

The human gut microbiota are the microorganisms (generally bacteria and archaea) that live in the digestive tracts of humans. Due to their numerous functions, the gut microbiota can be considered a virtual organ of the body, playing a pivotal role in health maintenance. Dietary habits contribute to gut microbiota composition, and evidence from observational and intervention studies suggest that vegan diets may promote health, potentially through affecting the diverse ecosystem of beneficial bacteria in the gut. A systematic literature search was conducted on PubMed and Scopus to identify studies investigating the microbiota composition in vegans. Vegans are defined as people excluding food products that are derived from animals from their diet. Nine observational studies were identified. The main outcome of the systematic review was an increase in Bacteroidetes on the phylum level and a higher abundance of Prevotella on the genus level. In conclusion, the present systematic literature review highlighted some benefits of a vegan diet but also demonstrated the complexity of evaluating results from gut microbiota research. The available evidence only consisted of cross-sectional studies, therefore suggesting the need for well-designed randomised controlled trials. Furthermore, the quality assessment of the studies included in the review suggested a lack of standardised and validated methods for participant selection as well as for faecal sampling and faecal analysis.

Fecal Metabolome Signature in the HIV-1 Elite Control Phenotype: Enrichment of Dipeptides Acts as an HIV-1 Antagonist but a Prevotella Agonist.

HIV-1 elite controllers (EC) are a rare group among HIV-1-infected individuals who can naturally control viral replication for a prolonged period. Due to their heterogeneous nature, no universal mechanism could be attributed to the EC status; instead, several host and viral factors have been discussed as playing a role. In this study, we investigated the fecal metabolome and microbiome in a Swedish cohort of EC (n = 14), treatment-naive viremic progressors (VP; n = 16), and HIV-negative individuals (HC; n = 12). Fecal untargeted metabolomics was performed by four ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). Molecular docking and biochemical microscale thermophoresis (MST) were used to describe the peptide-metabolite interactions. Single-cycle infectivity assays were performed in TZM-Bl cell lines using CCR5- and CXCR4-tropic HIV-1 strains. The microbiome analysis was performed using 16S rRNA sequencing. Th effects of metabolites on bacterial species viability were determined using several clinical isolates. We observed an enrichment of dipeptides in EC compared to VP and HC (adjusted P < 0.05). In silico analysis by molecular docking, in vitro biochemical assays, and ex vivo infection assays identified anti-HIV-1 properties for two dipeptides (WG and VQ) that could bind to the HIV-1 gp120, of which WG was more potent. The microbiome analysis identified enrichment of the genus Prevotella in EC, and these dipeptides supported bacterial growth of the genus Prevotella in vitro. The enrichments of the dipeptides and higher abundance of Prevotella have a distinct mechanism of elite control status in HIV-1 infection that influences host metabolism. IMPORTANCE HIV-1 elite controllers (EC) are a rare group among HIV-1-infected individuals who can naturally control viral replication for a prolonged period. Due to their heterogeneous nature, no universal mechanism could be attributed to the EC status; instead, several host and viral factors have been discussed as playing a role. In this study, we investigated the fecal metabolome and microbiome in a Swedish cohort of EC, treatment-naive viremic progressors (VP), and HIV-negative individuals (HC). We observed an enrichment of dipeptides in EC compared to the other two study groups. In silico and in vitro analyses identified anti-HIV-1 properties for two dipeptides that could bind to the HIV-1 gp120 and act as an HIV-1 antagonist. Furthermore, these dipeptides supported bacterial growth of the genus Prevotella in vitro that was enriched in EC, which influences host metabolism. Thus, increased levels of both dipeptides and Prevotella could provide beneficial effects for EC.

Chicken-eaters and pork-eaters have different gut microbiota and tryptophan metabolites

This study was aimed to evaluate the differences in the composition of gut microbiota, tryptophan metabolites and short-chain fatty acids in feces between volunteers who frequently ate chicken and who frequently ate pork. Twenty male chicken-eaters and 20 male pork-eaters of 18 and 30 years old were recruited to collect feces samples for analyses of gut microbiota composition, short-chain fatty acids and tryptophan metabolites. Chicken-eaters had more diverse gut microbiota and higher abundance of Prevotella 9, Dialister, Faecalibacterium, Megamonas, and Prevotella 2. However, pork-eaters had higher relative abundance of Bacteroides, Faecalibacterium, Roseburia, Dialister, and Ruminococcus 2. In addition, chicken-eaters had high contents of skatole and indole in feces than pork-eaters, as well as higher contents of total short chain fatty acids, in particular for acetic acid, propionic acid, and branched chain fatty acids. The Spearman’s correlation analysis revealed that the abundance of Prevotella 2 and Prevotella 9 was positively correlated with levels of fecal skatole, indole and short-chain fatty acids. Thus, intake of chicken diet may increase the risk of skatole- and indole-induced diseases by altering gut microbiota.

Associations Between Dysmenorrhea Symptom-Based Phenotypes and Vaginal Microbiome: A Pilot Study.

Dysmenorrhea is highly prevalent; it places women at risk for other chronic pain conditions. There is a high degree of individual variability in menstrual pain severity, the number of painful sites, and co-occurring gastrointestinal symptoms. Distinct dysmenorrhea symptom-based phenotypes were previously identified, but the biological underpinnings of these phenotypes are less known. One underexplored contributor is the vaginal microbiome. The vaginal microbiota differs significantly among reproductive-age women and may modulate as well as amplify reproductive tract inflammation, which may contribute to dysmenorrhea symptoms. The objective of this study was to examine associations between dysmenorrhea symptom-based phenotypes and vaginal microbiome compositions on- and off-menses. We conducted a prospective, longitudinal, pilot study of 20 women (aged 15-24 years) grouped into three dysmenorrhea symptom-based phenotypes: "mild localized pain," "severe localized pain," and "severe multiple pain and gastrointestinal symptoms." Over one menstrual cycle, participants provided vaginal swabs when they were on- and off-menses. We assayed the vaginal microbiome using 16S rRNA gene sequencing. Permutational multivariate analysis of variance tests were used to compare microbiome compositions across phenotypes, with heat maps generated to visualize the relative abundance of bacterial taxa. The vaginal microbiome compositions (n = 40) were different across the three phenotypes. After separating the on-menses (n = 20) and off-menses (n = 20) specimens, the statistically significant difference was seen on-menses, but not off-menses. Compared to the "mild localized pain" phenotype, participants in the "multiple severe symptoms" phenotype had a lower lactobacilli level and a higher abundance of Prevotella, Atopobium, and Gardnerella when on-menses. We also observed trends of differences across phenotypes in vaginal microbiome change from off- to on-menses. The study provides proof-of-concept data to support larger studies on associations between dysmenorrhea symptom-based phenotypes and vaginal microbiome that might lead to new intervention targets and/or biomarkers for dysmenorrhea. This line of research has the potential to inform precision dysmenorrhea treatment that can improve women's quality of life.