Microbiome Analysis of Mucosal Ileoanal Pouch in Ulcerative Colitis Patients Revealed Impairment of the Pouches Immunometabolites

The pathogenesis of ulcerative colitis (UC) is unknown, although genetic loci and altered gut microbiota have been implicated. Up to a third of patients with moderate to severe UC require proctocolectomy with ileal pouch ano-anastomosis (IPAA). We aimed to explore the mucosal microbiota of UC patients who underwent IPAA. Methods: For microbiome analysis, mucosal specimens were collected from 34 IPAA individuals. Endoscopic and histological examinations of IPAA were normal in 21 cases, while pouchitis was in 13 patients. 19 specimens from the healthy control (10 from colonic and 9 from ileum) were also analyzed. Data were analyzed using an ensemble of software packages: QIIME2, coda-lasso, clr-lasso, PICRUSt2, and ALDEx2. Results: IPAA specimens had significantly lower bacterial diversity as compared to normal. The microbial composition of the normal pouch was also decreased also when compared to pouchitis. Faecalibacterium prausnitzii, Gemmiger formicilis, Blautia obeum, Ruminococcus torques, Dorea formicigenerans, and an unknown species from Roseburia were the most uncommon in pouch/pouchitis, while an unknown species from Enterobacteriaceae was over-represented. Propionibacterium acnes and Enterobacteriaceae were the species most abundant in the pouchitis and in the normal pouch, respectively. Predicted metabolic pathways among the IPAA bacterial communities revealed an important role of immunometabolites such as SCFA, butyrate, and amino acids. Conclusions: Our findings showed specific bacterial signature hallmarks of dysbiosis and could represent bacterial biomarkers in IPAA patients useful to develop novel treatments in the future by modulating the gut microbiota through the administration of probiotic immunometabolites-producing bacterial strains and the addition of specific prebiotics and the faecal microbiota transplantation.

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10 THE ROLE OF DIETARY L-SERINE IN THE REGULATION OF INTESTINAL MUCUS BARRIER DURING INFLAMMATION

Inflammatory Bowel Diseases ◽

10.1093/ibd/zaa010.110 ◽

2020 ◽

Vol 26 (Supplement_1) ◽

pp. S42-S42

Author(s):

Kohei Sugihara ◽

Nobuhiko Kamada

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Gut Microbiota ◽

Control Diet ◽

Bacterial Strains ◽

Germ Free ◽

Intestinal Mucus ◽

Gnotobiotic Mice ◽

Mucus Barrier

Abstract Background Recent accumulating evidence suggests that amino acids have crucial roles in the maintenance of intestinal homeostasis. In inflammatory bowel disease (IBD), amino acid metabolism is changed in both host and the gut microbiota. Among amino acids, L-serine plays a central role in several metabolic processes that are essential for the growth and survival of both mammalian and bacterial cells. However, the role of L-serine in intestinal homeostasis and IBD remains incompletely understood. In this study, we investigated the effect of dietary L-serine on intestinal inflammation in a murine model of colitis. Methods Specific pathogen-free (SPF) mice were fed either a control diet (amino acid-based diet) or an L-serine-deficient diet (SDD). Colitis was induced by the treatment of dextran sodium sulfate (DSS). The gut microbiome was analyzed by 16S rRNA sequencing. We also evaluate the effect of dietary L-serine in germ-free mice and gnotobiotic mice that were colonized by a consortium of non-mucolytic bacterial strains or the consortium plus mucolytic bacterial strains. Results We found that the SDD exacerbated experimental colitis in SPF mice. However, the severity of colitis in SDD-fed mice was comparable to control diet-fed mice in germ-free condition, suggesting that the gut microbiota is required for exacerbation of colitis caused by the restriction of dietary L-serine. The gut microbiome analysis revealed that dietary L-serine restriction fosters the blooms of a mucus-degrading bacterium Akkermansia muciniphila and adherent-invasive Escherichia coli in the inflamed gut. Consistent with the expansion of mucolytic bacteria, SDD-fed mice showed a loss of the intestinal mucus layer. Dysfunction of the mucus barrier resulted in increased intestinal permeability, thereby leading to bacterial translocation to the intestinal mucosa, which subsequently increased the severity of colitis. The increased intestinal permeability and subsequent bacterial translocation were observed in SDD-fed gnotobiotic mice that colonized by mucolytic bacteria. In contrast, dietary L-serine restriction did not alter intestinal barrier integrity in gnotobiotic mice that colonized only by non-mucolytic bacteria. Conclusion Our results suggest that dietary L-serine regulates the integrity of the intestinal mucus barrier during inflammation by limiting the expansion of mucus degrading bacteria.

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Fecal microbiota dynamics during disease activity and remission in newly diagnosed and established ulcerative colitis

Scientific Reports ◽

10.1038/s41598-021-87973-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lena Öhman ◽

Anders Lasson ◽

Anna Strömbeck ◽

Stefan Isaksson ◽

Marcus Hesselmar ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiota ◽

Disease Activity ◽

Temporal Dynamics ◽

Fecal Microbiota ◽

Disease Stage ◽

Dietary Interventions ◽

Microbial Composition ◽

Fecal Samples ◽

Specific Species

AbstractPatients with ulcerative colitis (UC) have an altered gut microbiota composition, but the microbial relationship to disease activity needs to be further elucidated. Therefore, temporal dynamics of the fecal microbial community during remission and flare was determined. Fecal samples were collected at 2–6 time-points from UC patients during established disease (cohort EST) and at diagnosis (cohort NEW). Sampling range for cohort EST was 3–10 months and for cohort NEW 36 months. Relapses were monitored for an additional three years for cohort EST. Microbial composition was assessed by Genetic Analysis GA-map Dysbiosis Test, targeting ≥ 300 bacteria. Eighteen patients in cohort EST (8 with maintained remission and 10 experiencing a flare), provided 71 fecal samples. In cohort NEW, 13 patients provided 49 fecal samples. The microbial composition showed no clustering related to disease activity in any cohort. Microbial dissimilarity was higher between than within patients for both cohorts, irrespective of presence of a flare. Microbial stability within patients was constant over time with no major shift in overall composition nor modification in the abundance of any specific species. Microbial composition was not affected by intensified medical treatment or linked to future disease course. Thus in UC, the gut microbiota is highly stable irrespective of disease stage, disease activity or treatment escalation. This suggests that prolonged dietary interventions or repeated fecal transplantations are needed to be able to induce permanent alterations of the gut microbiota.

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Role of Biological Sex in the Cardiovascular-Gut Microbiome Axis

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.759735 ◽

2022 ◽

Vol 8 ◽

Author(s):

Shuangyue Li ◽

Georgios Kararigas

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Microbial Composition ◽

Biological Sex ◽

Technological Advances ◽

Host Health ◽

Health And Disease ◽

And Function ◽

Insight Into

There has been a recent, unprecedented interest in the role of gut microbiota in host health and disease. Technological advances have dramatically expanded our knowledge of the gut microbiome. Increasing evidence has indicated a strong link between gut microbiota and the development of cardiovascular diseases (CVD). In the present article, we discuss the contribution of gut microbiota in the development and progression of CVD. We further discuss how the gut microbiome may differ between the sexes and how it may be influenced by sex hormones. We put forward that regulation of microbial composition and function by sex might lead to sex-biased disease susceptibility, thereby offering a mechanistic insight into sex differences in CVD. A better understanding of this could identify novel targets, ultimately contributing to the development of innovative preventive, diagnostic and therapeutic strategies for men and women.

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Modulation of instinal microbiom in the formation and progression of ulterative colitis.

Annals of the Russian academy of medical sciences ◽

10.15690/vramn1238 ◽

2020 ◽

Vol 75 (6) ◽

pp. 577-584

Author(s):

G. R. Bikbavova ◽

M. A. Livzan

Keyword(s):

Ulcerative Colitis ◽

Short Chain Fatty Acids ◽

Intestinal Wall ◽

Intestinal Microbiome ◽

Industrial Society ◽

Microbial Composition ◽

Microbiome Composition ◽

Available Information ◽

Post Industrial

In recent decades, an increase in the incidence of ulcerative colitis has been observed throughout the world. The purpose of this review is to generalize the available information on the influence of environmental factors and intestinal microbiome on the occurrence and development of ulcerative colitis, the role of bacteria metabolism products in the pathogenesis of the disease. Studied literature, we came to the conclusion that lifestyle in the era of post-industrial society has a significant impact on the microbial composition of the intestine and leads to changes in its diversity in patients suffering from ulcerative colitis. The changes include a decrease in the number of residential flora with anti-inflammatory activity, which synthesize short-chain fatty acids, and an increase in the number of potentially pathogenic and pathogenic microorganisms. Within the phylums Firmicutes and Proteobacteria, the proportional ratio changes. The combination of aggression factors (deterioration of the intestinal microbiome composition, the presence of aggressive intestinal metabolites) leads to intestinal mucosa permeability disfunction, impairing its barrier function. Food and bacterial agents can penetrate deeper layers of the intestinal wall through mucosal defects, which then stimulate the development of inflammatory and immune responses.

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Pathophysiological role of Atg5 in human ulcerative colitis

Intestinal Research ◽

10.5217/ir.2019.00120 ◽

2020 ◽

Vol 18 (4) ◽

pp. 421-429

Author(s):

Razieh Ardali ◽

Nasrin Kazemipour ◽

Saeed Nazifi ◽

Kamran Bagheri Lankarani ◽

Iman Razeghian Jahromi ◽

...

Keyword(s):

Ulcerative Colitis ◽

Enzyme Linked Immunosorbent Assay ◽

Blood Samples ◽

Significant Difference ◽

Colon Biopsy ◽

Pathophysiological Role ◽

Healthy Control ◽

Inflammatory Bowel ◽

Insight Into

Background/Aims: Ulcerative colitis (UC), along with Crohn’s disease, is one of the main types of inflammatory bowel disease (IBD). On the other hand, deregulated autophagy is involved in many chronic diseases, including IBD. In this study, we aimed to investigate the role of Atg5 and microRNA-181a (miR-181a) in the pathophysiology of UC. Methods: Colon biopsy, stool, and blood samples of 6 men and 9 women were confirmed for UC. Also, 13 men and 17 women were selected as healthy control (HC). Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were used to measure the Atg-5 content of the colon biopsies. Besides, the serum and stool levels of Atg5 were measured using ELISA. Moreover, the total RNA of blood cells was extracted and evaluated for the expression of miR-181a.Results: We found 1.2 ng/mL versus 0.46 ng/mL, 0.34 ng/mL versus 0.24 ng/mL, and 0.082 ng/mL versus 0.062 ng/mL of Atg5 in stool, intestinal tissue, and serum of UC and HCs, respectively. There was no significant difference in the expression of miR-181a in the blood samples of UC and HCs. Immunohistochemistry showed high positivity without any significant difference between the 2 groups in the quantitative analysis.Conclusions: The significant difference observed between the stool Atg5 content of the HCs and UC patients may provide new insight into using this protein as a diagnostic biomarker, however, considering the small size of our studied population further studies are needed.

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P076 Role of gut microbiota in mediating the effects of thiopurines

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.205 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S173-S174

Author(s):

M Franzin ◽

M Lucafò ◽

C Lagatolla ◽

G Stocco ◽

G Decorti

Keyword(s):

Gut Microbiota ◽

Growth Phase ◽

Statistical Significance ◽

Jurkat Cells ◽

Uv Spectrophotometry ◽

Bacterial Strains ◽

Cytotoxic Effects ◽

E Coli

Abstract Background A general consensus exists that patients with inflammatory bowel disease (IBD) present compositional changes in the gut microbiota (dysbiosis), including an increase in the abundance of Enterobacteriaceae. Thiopurine drugs are commonly used in the maintenance of remission in IBD. In this context, the purpose of the project is to explore the role of candidate bacterial strains in mediating the effects of thiopurines in vitro. Methods Azathioprine (AZA), mercaptopurine (MP) and thioguanine (TG) (400 µM) were incubated in minimal salts medium (M9) in presence or not of E. coli, S. enterica and K. pneumoniae and of their growth phase broths (GPB) for 4 h at 37°C. The viability of NALM6 (B cells) and JURKAT (T cells) exposed to serial dilution of drugs (ranging from 0.2 to 15 μM of AZA, from 0.3 to 20 μM of MP, from 0.08 to 5 μM of TG) previously incubated or not with bacteria and with their GPB was determined by the MTT assay. Absorbance peaks of thiopurines were analysed by UV spectrophotometry. Statistical significance was assessed by two-way ANOVA and Bonferroni’s post-test for MTT tests and by one-way ANOVA for UV spectra. Results In NALM6 cells, the cytotoxic effects of 15 μM of AZA, 2.5 μM of MP and 1.25 μM of TG decreased significantly (p < 0.001) after incubation with K. pneumoniae (respectively 45 ± 2.9%; 34 ± 2.5%% and 21 ± 0.6%) and its GPB (respectively 41 ± 7.7%; 41 ± 5.1% and 27 ± 3.5%) compared with the drugs not previously exposed (respectively 76 ± 2.3%; 69 ± 1.7% and 43 ± 3.8%). In JURKAT cells, the cytotoxic effects of 15 μM of AZA, 2.5 μM of MP and 1.25 μM of TG decreased significantly (p < 0.001) after incubation with K. pneumoniae (respectively 46 ± 2.8%; 38 ± 1.29% and 19 ± 3.3%) and its GPB (respectively 49 ± 9.4%; 38 ± 1.5% and 26 ± 1.5%) in comparison with the drugs not exposed (respectively 75 ± 4.0%; 50 ± 3.5% and 54 ± 4.0%). E. coli and S. enterica did not affect the cytotoxicity of the thiopurines. UV analysis evidenced a reduction of absorbance peaks of AZA (21 ± 0.05%), MP (32 ± 0.015%) and TG (30 ± 0.03%) after incubation with K. pneumoniae but not with its growth phase broth (GPB). Conclusion The activity of thiopurines decreased after incubation with both K. pneumoniae and its GPB. UV analysis suggested that the lower cytotoxicity of thiopurines exposed to the bacterial strain is due to the reduction of the concentration of the drugs exposed to K. pneumoniae. Moreover, the reduction of drug availability after the exposure to GPB could be explained with a possible interaction between thiopurines and capsular polysaccharides released by the bacteria.

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Potential Role of the Microbiome in Acne: A Comprehensive Review

Journal of Clinical Medicine ◽

10.3390/jcm8070987 ◽

2019 ◽

Vol 8 (7) ◽

pp. 987 ◽

Cited By ~ 24

Author(s):

Lee ◽

Byun ◽

Kim

Keyword(s):

Gut Microbiota ◽

Skin Inflammation ◽

Skin Condition ◽

Metagenomic Sequencing ◽

Depression And Anxiety ◽

Microbial Composition ◽

Gut Microbes ◽

Cutibacterium Acnes ◽

Pathogenic Process

Acne is a highly prevalent inflammatory skin condition involving sebaceous sties. Although it clearly develops from an interplay of multiple factors, the exact cause of acne remains elusive. It is increasingly believed that the interaction between skin microbes and host immunity plays an important role in this disease, with perturbed microbial composition and activity found in acne patients. Cutibacterium acnes (C. acnes; formerly called Propionibacterium acnes) is commonly found in sebum-rich areas and its over-proliferation has long been thought to contribute to the disease. However, information provided by advanced metagenomic sequencing has indicated that the cutaneous microbiota in acne patients and acne-free individuals differ at the virulent-specific lineage level. Acne also has close connections with the gastrointestinal tract, and many argue that the gut microbiota could be involved in the pathogenic process of acne. The emotions of stress (e.g., depression and anxiety), for instance, have been hypothesized to aggravate acne by altering the gut microbiota and increasing intestinal permeability, potentially contributing to skin inflammation. Over the years, an expanding body of research has highlighted the presence of a gut–brain–skin axis that connects gut microbes, oral probiotics, and diet, currently an area of intense scrutiny, to acne severity. This review concentrates on the skin and gut microbes in acne, the role that the gut–brain–skin axis plays in the immunobiology of acne, and newly emerging microbiome-based therapies that can be applied to treat acne.

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Gut Microbiota Changes and Their Correlation with Cognitive and Neuropsychiatric Symptoms in Alzheimer’s Disease

Journal of Alzheimer s Disease ◽

10.3233/jad-201497 ◽

2021 ◽

pp. 1-13

Author(s):

Yunzhe Zhou ◽

Yan Wang ◽

Meina Quan ◽

Huiying Zhao ◽

Jianping Jia

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Gut Microbiota ◽

Ribosomal Rna ◽

Neuropsychiatric Symptoms ◽

Clinical Dementia Rating ◽

Microbial Composition ◽

Healthy Control ◽

And Behavior ◽

State Examination

Background: Gut microbiota can influence human brain function and behavior. Recent studies showed that gut microbiota might play an important role in the pathogenesis of Alzheimer’s disease (AD). Objective: To investigate the composition of gut microbiota in AD patients and their association with cognitive function and neuropsychiatric symptoms (NPS). Methods: The fecal samples from 60 AD patients (30 with NPS and 30 without NPS) and 32 healthy control subjects (HC) were collected and analyzed by 16S ribosomal RNA sequencing. The functional variations of gut microbiota were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States. The correlation between different bacterial taxa and cognitive (Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR)), and NPS measures were analyzed. Results: The fecal microbial composition of AD patients was quite distinct from HC. Bifidobacterium, Sphingomonas, Lactobacillus, and Blautia were enriched, while Odoribacter, Anaerobacterium, and Papillibacter were reduced. AD patients with NPS showed decreased Chitinophagaceae, Taibaiella, and Anaerobacterium compared with those without NPS. Functional pathways were different between AD and HC, and between AD patients with and without NPS. Correlation analysis showed that Sphingomonas correlated negatively with MMSE; Anaerobacterium and Papillibacter correlated positively with MMSE and negatively with CDR. Cytophagia, Rhodospirillaceae, and Cellvibrio correlated positively with NPS, while Chitinophagaceae, Taibaiella, and Anaerobacterium correlated negatively with NPS. Conclusion: AD patients have gut microbiota alterations related to cognition, and differential taxa between AD patients with and without NPS associated differently with NPS domains, which helps further understand the pathogenesis of AD and explore potential therapeutic targets.

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Diversification of Type VI Secretion System Toxins Reveals Ancient Antagonism among Bee Gut Microbes

mBio ◽

10.1128/mbio.01630-17 ◽

2017 ◽

Vol 8 (6) ◽

Cited By ~ 36

Author(s):

Margaret I. Steele ◽

Waldan K. Kwong ◽

Marvin Whiteley ◽

Nancy A. Moran

Keyword(s):

Escherichia Coli ◽

Gut Microbiota ◽

Microbial Communities ◽

Protein Complexes ◽

Bacterial Species ◽

Bacterial Strains ◽

Secretion Systems ◽

Type Vi Secretion ◽

Immunity Genes

ABSTRACT Microbial communities are shaped by interactions among their constituent members. Some Gram-negative bacteria employ type VI secretion systems (T6SSs) to inject protein toxins into neighboring cells. These interactions have been theorized to affect the composition of host-associated microbiomes, but the role of T6SSs in the evolution of gut communities is not well understood. We report the discovery of two T6SSs and numerous T6SS-associated Rhs toxins within the gut bacteria of honey bees and bumble bees. We sequenced the genomes of 28 strains of Snodgrassella alvi, a characteristic bee gut microbe, and found tremendous variability in their Rhs toxin complements: altogether, these strains appear to encode hundreds of unique toxins. Some toxins are shared with Gilliamella apicola, a coresident gut symbiont, implicating horizontal gene transfer as a source of toxin diversity in the bee gut. We use data from a transposon mutagenesis screen to identify toxins with antibacterial function in the bee gut and validate the function and specificity of a subset of these toxin and immunity genes in Escherichia coli. Using transcriptome sequencing, we demonstrate that S. alvi T6SSs and associated toxins are upregulated in the gut environment. We find that S. alvi Rhs loci have a conserved architecture, consistent with the C-terminal displacement model of toxin diversification, with Rhs toxins, toxin fragments, and cognate immunity genes that are expressed and confer strong fitness effects in vivo. Our findings of T6SS activity and Rhs toxin diversity suggest that T6SS-mediated competition may be an important driver of coevolution within the bee gut microbiota. IMPORTANCE The structure and composition of host-associated bacterial communities are of broad interest, because these communities affect host health. Bees have a simple, conserved gut microbiota, which provides an opportunity to explore interactions between species that have coevolved within their host over millions of years. This study examined the role of type VI secretion systems (T6SSs)—protein complexes used to deliver toxic proteins into bacterial competitors—within the bee gut microbiota. We identified two T6SSs and diverse T6SS-associated toxins in bacterial strains from bees. Expression of these genes is increased in bacteria in the bee gut, and toxin and immunity genes demonstrate antibacterial and protective functions, respectively, when expressed in Escherichia coli. Our results suggest that coevolution among bacterial species in the bee gut has favored toxin diversification and maintenance of T6SS machinery, and demonstrate the importance of antagonistic interactions within host-associated microbial communities. IMPORTANCE The structure and composition of host-associated bacterial communities are of broad interest, because these communities affect host health. Bees have a simple, conserved gut microbiota, which provides an opportunity to explore interactions between species that have coevolved within their host over millions of years. This study examined the role of type VI secretion systems (T6SSs)—protein complexes used to deliver toxic proteins into bacterial competitors—within the bee gut microbiota. We identified two T6SSs and diverse T6SS-associated toxins in bacterial strains from bees. Expression of these genes is increased in bacteria in the bee gut, and toxin and immunity genes demonstrate antibacterial and protective functions, respectively, when expressed in Escherichia coli. Our results suggest that coevolution among bacterial species in the bee gut has favored toxin diversification and maintenance of T6SS machinery, and demonstrate the importance of antagonistic interactions within host-associated microbial communities.

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Functional characterisation of gut microbiota and metabolism in Type 2 diabetes indicates that Clostridiales and Enterococcus could play a key role in the disease

10.1101/836114 ◽

2019 ◽

Author(s):

Marina Mora-Ortiz ◽

Alain Oregioni ◽

Sandrine P. Claus

Keyword(s):

Type 2 Diabetes ◽

Mouse Model ◽

Gut Microbiota ◽

Short Chain Fatty Acid ◽

Microbial Composition ◽

Functional Characterisation ◽

Branched Chain ◽

Acetate Butyrate

AbstractThere is growing evidence indicating that gut microbiota contributes to the development of metabolic syndrome and Type 2 Diabetes (T2D). The most widely-used model for T2D research is the leptin deficient db/db mouse model. Yet, a characterisation of the gut microbial composition in this model in relationship with the metabolism is lacking. The objectives of this study were to identify metabolomics and microbial modulations associated with T2D in the db/db mouse model. The majority of microbial changes observed included an increase of Enterobacteriaceae and a decrease of Clostridiales in diabetics. The metabolomics interrogation of caecum indicated a lower proteolytic activity in diabetics, who also showed higher Short-Chain Fatty Acid (SCFA) levels. In the case of faeces, the model identified 9 metabolites, the main ones were acetate, butyrate and Branched Chain Amino Acids (BCAAs). Finally, liver was the organ with more metabolic links with gut-microbiota followed by the Gut-Brain Axis (GBA). In conclusion, the interaction between Clostridiales and Enterococcus with caecal metabolism could play a key role in the onset and development of diabetes. Further studies should investigate whether the role of these bacteria is causal or co-occurring.

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