Evaluation of the gut microbiome in association with biological signatures of inflammation in murine polytrauma and shock

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.

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AB1232 ORAL DYSBIOSIS REFLECTS THE IMMUNOLOGICAL ALTERATION OF RA REGARDING TO ACPA AND HLA DRB1*SE: NAGASAKI ISLAND STUDY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5147 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1907.2-1907

Author(s):

Y. Tsuji ◽

M. Tamai ◽

S. Morimoto ◽

D. Sasaki ◽

M. Nagayoshi ◽

...

Keyword(s):

Beta Diversity ◽

Healthy Subjects ◽

Microbial Community Composition ◽

Alpha Diversity ◽

Enzyme Linked Immunosorbent Assay ◽

Rrna Gene ◽

Oral Microbiota ◽

Unifrac Distance ◽

Alpha And Beta Diversity ◽

The Difference

Background:Anti-citrullinated protein antibody (ACPA) production is observed in several organs even prior to the onset of rheumatoid arthritis (RA), and oral mucosa is considered to be one of the important tissues. The presence of HLA-DRB1*SE closely associates with ACPA production. Saliva is considered to reflect the oral microbiota including periodontal disease. Alteration of oral microbiota of RA becomes to be normalized by DMARDs treatment, however, the interaction of HLA-DRB1*SE, ACPA and oral microbiota of RA patients remains to be elucidated.Objectives:The Nagasaki Island Study, which had started in 2014 collaborating with Goto City, is intended for research of the preclinical stage of RA, including ACPA/HLA genotype screening and ultrasound and magnetic resonance imaging examinations in high-risk subjects. Using the samples accumulated in this cohort, we have tried to investigate the difference of oral microbiota among RA patients and healthy subjects regarding to ACPA and HLA-DRB1*SE.Methods:Blood and salivary samples were obtained from 1422 subjects out of 4276 who have participated in the Nagasaki Island Study from 2016 to 2018. ACPA positivity was 1.7 % in total. Some of RA patients resided in Goto City participated in the Nagasaki Island Study. At this point, we selected 291 subjects, who were ACPA positive non-RA healthy subjects (n=22) and patients with RA (n=33, 11 subjects were ACPA positive and 22 ACPA negative respectively) as the case, age and gender matched ACPA negative non-RA healthy subjects (n=236) as the control. ACPA was measured by an enzyme-linked immunosorbent assay, and HLA genotyping was quantified by next-generation sequencing (Ref.1). The operational taxonomic unit (OUT) analysis using 16S rRNA gene sequencing were performed. The richness of microbial diversity within-subject (alpha diversity) was scaled via Shannon entropy. The dissimilarity between microbial community composition was calculated using Bray-Curtis distance as a scale, and differences between groups (beta diversity) were tested by permutational multivariate analysis of variance (PERMANOVA). In addition, UniFrac distance calculated in consideration of the distance on the phylogenetic tree were performed.Results:Median age 70 y.o., % Female 58.8 %. Among RA and non-RA subjects, not alpha diversity but beta diversity was statistically significance (p=0.022, small in RA). In RA subjects, both alpha and beta diversity is small (p<0.0001), especially significant in ACPA positive RA (Figure 1). Amongt RA subjects, presence of HLA-DRB1*SE did not show the difference but the tendency of being small of alpha diversity (p=0.29).Conclusion:Our study has suggested for the first time the association of oral microbiota alteration with the presence of ACPA and HLA-DRB1*SE. Oral dysbiosis may reflect the immunological status of patients with RA.References:[1]Kawaguchi S, et al. Methods Mol Biol 2018;1802: 22Disclosure of Interests:None declared

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Gut microbiota composition is associated with narcolepsy type 1

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000000896 ◽

2020 ◽

Vol 7 (6) ◽

pp. e896

Author(s):

Alexandre Lecomte ◽

Lucie Barateau ◽

Pedro Pereira ◽

Lars Paulin ◽

Petri Auvinen ◽

...

Keyword(s):

Community Structure ◽

Gut Microbiota ◽

Bacterial Communities ◽

Beta Diversity ◽

Alpha Diversity ◽

Amplicon Sequencing ◽

Rrna Gene ◽

Differential Abundance ◽

Alpha And Beta Diversity

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.

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Gut Microbiome Analysis As A Non-Invasive Tool for the Early Diagnosis of Cholangiocarcinoma

10.21203/rs.3.rs-147842/v1 ◽

2021 ◽

Author(s):

Jialiang Li ◽

Xueyan Li ◽

Sina Zhang ◽

Chen Jin ◽

Zixia Lin ◽

...

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Microbial Community Composition ◽

Intestinal Flora ◽

Alpha Diversity ◽

16S Rrna Gene Sequencing ◽

Intestinal Microbiome ◽

Rrna Gene ◽

Non Invasive ◽

Hepatobiliary Cancer

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.

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

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.568 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Valentina Rodriguez Paris ◽

Nadeem O Kaakoush ◽

Samantha M Solon-Biet ◽

Melissa C Edwards ◽

William L Ledger ◽

...

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Beta Diversity ◽

Polycystic Ovary ◽

Cell Metabolism ◽

Consensus Sequence ◽

Alpha Diversity ◽

Operational Taxonomic Unit ◽

Intestinal Microbiome ◽

Alpha And Beta Diversity

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.

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Effect of Bovine MFGM and LF in Infant Formula on Gut Microbiome and Metabolome at Four Months of Age

Current Developments in Nutrition ◽

10.1093/cdn/nzab027 ◽

2021 ◽

Author(s):

Maciej Chichlowski ◽

Nicholas Bokulich ◽

Cheryl L Harris ◽

Jennifer L Wampler ◽

Fei Li ◽

...

Keyword(s):

Infant Formula ◽

Beta Diversity ◽

Milk Fat ◽

Alpha Diversity ◽

Illumina Miseq ◽

Rrna Gene ◽

Term Infants ◽

Linear Discriminant ◽

Alpha And Beta Diversity ◽

Metabolite Profiles

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 < 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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Gut Microbiome in Psoriasis: An Updated Review

Pathogens ◽

10.3390/pathogens9060463 ◽

2020 ◽

Vol 9 (6) ◽

pp. 463

Author(s):

Mariusz Sikora ◽

Albert Stec ◽

Magdalena Chrabaszcz ◽

Aleksandra Knot ◽

Anna Waskiel-Burnat ◽

...

Keyword(s):

Gut Microbiome ◽

Beta Diversity ◽

Large Scale ◽

Skin Diseases ◽

Intestinal Barrier ◽

Alpha Diversity ◽

Current Data ◽

Intestinal Microbiome ◽

Microbial Composition ◽

Alpha And Beta Diversity

(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.

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Gut bacterial microbiota in patients with myasthenia gravis: results from the MYBIOM study

Therapeutic Advances in Neurological Disorders ◽

10.1177/17562864211035657 ◽

2021 ◽

Vol 14 ◽

pp. 175628642110356

Author(s):

Andreas Totzeck ◽

Elakiya Ramakrishnan ◽

Melina Schlag ◽

Benjamin Stolte ◽

Kathrin Kizina ◽

...

Keyword(s):

Gut Microbiota ◽

Myasthenia Gravis ◽

Healthy Volunteers ◽

Alpha Diversity ◽

Diversity Indices ◽

Rrna Gene ◽

Pilot Studies ◽

Variable Regions ◽

Alpha And Beta Diversity ◽

Significant Difference

Background: Myasthenia gravis (MG) is an autoimmune neuromuscular disease, with gut microbiota considered to be a pathogenetic factor. Previous pilot studies have found differences in the gut microbiota of patients with MG and healthy individuals. To determine whether gut microbiota has a pathogenetic role in MG, we compared the gut microbiota of patients with MG with that of patients with non-inflammatory and inflammatory neurological disorders of the peripheral nervous system (primary endpoint) and healthy volunteers (secondary endpoint). Methods: Faecal samples were collected from patients with MG ( n = 41), non-inflammatory neurological disorder (NIND, n = 18), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP, n = 6) and healthy volunteers ( n = 12). DNA was isolated from these samples, and the variable regions of the 16S rRNA gene were sequenced and statistically analysed. Results: No differences were found in alpha- and beta-diversity indices computed between the MG, NIND and CIDP groups, indicating an unaltered bacterial diversity and structure of the microbial community. However, the alpha-diversity indices, namely Shannon, Chao 1 and abundance-based coverage estimators, were significantly reduced between the MG group and healthy volunteers. Deltaproteobacteria and Faecalibacterium were abundant within the faecal microbiota of patients with MG compared with controls with non-inflammatory diseases. Conclusion: Although the overall diversity and structure of the gut microbiota did not differ between the MG, NIND and CIDP groups, the significant difference in the abundance of Deltaproteobacteria and Faecalibacterium supports the possible role of gut microbiota as a contributor to pathogenesis of MG. Further studies are needed to confirm these findings and to develop possible treatment strategies.

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Evidence supporting the microbiota–gut–brain axis in a songbird

Biology Letters ◽

10.1098/rsbl.2020.0430 ◽

2020 ◽

Vol 16 (11) ◽

pp. 20200430

Author(s):

Morgan C. Slevin ◽

Jennifer L. Houtz ◽

David J. Bradshaw ◽

Rindy C. Anderson

Keyword(s):

Gut Microbiome ◽

Beta Diversity ◽

Alpha Diversity ◽

Cloacal Swab ◽

Cognitive Tasks ◽

Captive Population ◽

Wild Populations ◽

Alpha And Beta Diversity ◽

Microbiome Research ◽

Host Development

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.

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PSI-10 Establishing a foundation to harvest the potential of the microbiome in poultry production

Journal of Animal Science ◽

10.1093/jas/skz258.594 ◽

2019 ◽

Vol 97 (Supplement_3) ◽

pp. 293-294

Author(s):

Camila S Marcolla ◽

Benjamin Willing

Keyword(s):

Microbial Community ◽

Gut Microbiota ◽

Community Composition ◽

Relative Abundance ◽

Microbial Community Composition ◽

Alpha Diversity ◽

Poultry Production ◽

Microbiota Composition ◽

Microbial Composition ◽

The Impact

Abstract This study aimed to characterize poultry microbiota composition in commercial farms using 16S rRNA sequencing. Animals raised in sanitized environments have lower survival rates when facing pathogenic challenges compared to animals naturally exposed to commensal organisms. We hypothesized that intensive rearing practices inadvertently impair chicken exposure to microbes and the establishment of a balanced gut microbiota. We compared gut microbiota composition of broilers (n = 78) and layers (n = 20) from different systems, including commercial intensive farms with and without in-feed antibiotics, organic free-range farms, backyard-raised chickens and chickens in an experimental farm. Microbial community composition of conventionally raised broilers was significantly different from antibiotic-free broilers (P = 0.012), from broilers raised outdoors (P = 0.048) and in an experimental farm (P = 0.006) (Fig1). Significant community composition differences were observed between antibiotic-fed and antibiotic-free chickens (Fig2). Antibiotic-free chickens presented higher alpha-diversity, higher relative abundance of Deferribacteres, Fusobacteria, Bacteroidetes and Actinobacteria, and lower relative abundance of Firmicutes, Clostridiales and Enterobacteriales than antibiotic-fed chickens (P < 0.001) (Fig3). Microbial community composition significantly changed as birds aged. In experimental farm, microbial community composition was significant different for 7, 21 and 35 day old broilers (P < 0.001), and alpha diversity increased from 7 to 21d (P < 0.024), but not from 21 to 35d; whereas, in organic systems, increases in alpha-diversity were observed from 7d to 21d, and from 21d to 35d (P < 0.05). Broilers and layers raised together showed no differences in microbiota composition and alpha diversity (P > 0.8). It is concluded that production practices consistently impact microbial composition, and that antibiotics significantly reduces microbial diversity. We are now exploring the impact of differential colonization in a controlled setting, to determine the impact of the microbes associated with extensively raised chickens. This study will support future research and the development of methods to isolate and introduce beneficial microbes to commercial systems.

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Community composition and development of the post-weaning piglet gut microbiome

10.21203/rs.3.rs-60981/v1 ◽

2020 ◽

Author(s):

Daniela Gaio ◽

Matthew Z DeMaere ◽

Kay Anantanawat ◽

Graeme J Eamens ◽

Michael Liu ◽

...

Keyword(s):

Microbial Community ◽

Gut Microbiota ◽

Community Composition ◽

Antibiotic Treatment ◽

Gut Microbiome ◽

Treatment Effects ◽

Sequence Data ◽

Microbial Community Composition ◽

Dominant Factor ◽

Microbial Composition

Abstract BackgroundEarly weaning and intensive farming practices predispose piglets to the development of infectious and often lethal diseases, against which antibiotics are used. Besides contributing to the build-up of antimicrobial resistance, antibiotics are known to modulate the gut microbial composition. Studies have previously investigated the effects of probiotics as alternatives to antibiotic treatment for the prevention of post-weaning diarrhea. In order to describe the post-weaning gut microbiota, and the effects of two probiotics formulations and of intramuscular antibiotic treatment on the gut microbiota, we processed over 800 faecal time-series samples from 126 piglets and 42 sows, generating over 8Tbp of metagenomic shotgun sequence data. Here we describe the animal trial procedures, the generation of our metagenomic dataset and the analysis of the microbial community composition using a phylogenetic framework.ResultsFactors such as age, litter effects, and breed, by significantly correlating with gut microbial community shifts, can be major confounding factors in the assessment of treatment effects. Intramuscular antibiotic treatment and probiotic treatments were found to correlate with alpha and beta diversity, as well as with a transient establishment of Mollicutes and Lactobacillales, respectively. We found the abundance of certain taxa to correlate with weight gain.ConclusionsOur findings demonstrate that breed, litter, and age, are important contributors to variation in the community composition, and that treatment effects of the antibiotic and probiotic treatments were subtle, while host age was the dominant factor in shaping the gut microbiota of piglets after weaning. The current study shows, by means of a phylogenetic diversity framework, that the post-weaning pig gut microbiome appears to follow a highly structured developmental program with characteristic post-weaning changes that can distinguish hosts that were born as little as two days apart in the second month of life.

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