scholarly journals Cooperation between host immunity and the gut bacteria is essential for helminth-evoked suppression of colitis

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Adam Shute ◽  
Blanca E. Callejas ◽  
ShuHua Li ◽  
Arthur Wang ◽  
Timothy S. Jayme ◽  
...  
Keyword(s):  
Short Chain Fatty Acids ◽  
Gut Bacteria ◽  
Hymenolepis Diminuta ◽  
Helminth Parasites ◽  
Microbiome Composition ◽  
Intention To Treat ◽  
Community Profiling ◽  
Epithelial Cell Lines ◽  
Helminth Therapy

Abstract Background Studies on the inhibition of inflammation by infection with helminth parasites have, until recently, overlooked a key determinant of health: the gut microbiota. Infection with helminths evokes changes in the composition of their host’s microbiota: one outcome of which is an altered metabolome (e.g., levels of short-chain fatty acids (SCFAs)) in the gut lumen. The functional implications of helminth-evoked changes in the enteric microbiome (composition and metabolites) are poorly understood and are explored with respect to controlling enteric inflammation. Methods Antibiotic-treated wild-type, germ-free (GF) and free fatty-acid receptor-2 (ffar2) deficient mice were infected with the tapeworm Hymenolepis diminuta, then challenged with DNBS-colitis and disease severity and gut expression of the il-10 receptor-α and SCFA receptors/transporters assessed 3 days later. Gut bacteria composition was assessed by 16 s rRNA sequencing and SCFAs were measured. Other studies assessed the ability of feces or a bacteria-free fecal filtrate from H. diminuta-infected mice to inhibit colitis. Results Protection against disease by infection with H. diminuta was abrogated by antibiotic treatment and was not observed in GF-mice. Bacterial community profiling revealed an increase in variants belonging to the families Lachnospiraceae and Clostridium cluster XIVa in mice 8 days post-infection with H. diminuta, and the transfer of feces from these mice suppressed DNBS-colitis in GF-mice. Mice treated with a bacteria-free filtrate of feces from H. diminuta-infected mice were protected from DNBS-colitis. Metabolomic analysis revealed increased acetate and butyrate (both or which can reduce colitis) in feces from H. diminuta-infected mice, but not from antibiotic-treated H. diminuta-infected mice. H. diminuta-induced protection against DNBS-colitis was not observed in ffar2−/− mice. Immunologically, anti-il-10 antibodies inhibited the anti-colitic effect of H. diminuta-infection. Analyses of epithelial cell lines, colonoids, and colon segments uncovered reciprocity between butyrate and il-10 in the induction of the il-10-receptor and butyrate transporters. Conclusion Having defined a feed-forward signaling loop between il-10 and butyrate following infection with H. diminuta, this study identifies the gut microbiome as a critical component of the anti-colitic effect of this helminth therapy. We suggest that any intention-to-treat with helminth therapy should be based on the characterization of the patient’s immunological and microbiological response to the helminth.

scholarly journals A264 HELMINTH-INFECTION MOBILIZES HOST AND MICROBIAL FACTORS THAT CO-OPERATE TO SUPPRESS CHEMICAL-INDUCED COLITIS IN MICE

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 141-142
Author(s):  
A J Shute ◽  
B E Callejas Pina ◽  
T S Jayme ◽  
A Wang ◽  
A Buret ◽  
...  
Keyword(s):  
Drinking Water ◽  
Murine Model ◽  
Hymenolepis Diminuta ◽  
Model Systems ◽  
Epithelial Cell Line ◽  
Helminth Parasites ◽  
Critical Determinant ◽  
The Individual ◽  
Helminth Therapy

Abstract Background Infection with helminth parasites suppresses inflammation in murine model systems; for example, IL-10 is important in Hymenolepis diminuta-inhibition of DNBS-induced colitis. Bacteria-derived products can have anti-inflammatory effects. Given that infection with H. diminuta, or other parasitic worms, results in perturbation of the gut microbiota, the present study tested a role for bacteria in helminth-suppression of colitis by assessing reciprocity between IL-10 and butyrate signaling in the amelioration of colitis. Aims To determine if a functional relationship exists between IL-10 and butyrate in the inhibition of colitis observed following infection with the lumen-dwelling tapeworm, Hymenolepis diminuta. Methods Colitis was induced in male BALB/c mice by intra-rectal dinitrobenzene sulphonic acid (DNBS) (3 mg/~22g mouse), with necropsy and assessment 3 days later. Mice received either infection with five H. diminuta cysticercoids by gavage or daily butyrate enemas or acetate in their drinking water. Immunostaining assessed IL-10R protein expression on formalin-fixed sections of colon. The murine IEC4.1 epithelial cell line and epithelial organoids were treated with butyrate and mRNA for the IL10Rα chain assessed, as was colonic tissue from mice. Results Mice infected with H. diminuta or receiving butyrate enemas (n=8–12) were protected from DNBS-induced colitis as gauged by colon length, and macroscopic disease and histopathology scores. Addition of acetate to the drinking water resulted in a more modest anti-colitic effect. Suppression of colitis was accompanied by increased epithelial expression of IL-10 in butyrate- and H. diminuta-treated mice, with the later also showing upregulation of the IL-10R on lamina propria cells; an effect negated by co-treating the mice with broad spectrum antibiotics. In vitro analyses revealed increased IL10Rα mRNA in butyrate-treated epithelia (n=4). Conclusions This study begins to tease apart the host (i.e. IL-10) and bacterial (i.e. butyrate) molecules that mediate H. diminuta-evoked suppression of colitis in a murine model. These proof-of-principle data suggest that knowledge of the individual patient (i.e. immunological basis of their disease and their microbiota) may be a critical determinant of the success or failure of helminth therapy. Funding Agencies CAG, CCCNSERC

scholarly journals Young mice expel the tapeworm Hymenolepis diminuta and are protected from colitis by triggering a memory response with worm antigen

2018 ◽  
Vol 314 (4) ◽  
pp. G461-G470 ◽  
Author(s):  
Toshio Arai ◽  
Fernando Lopes ◽  
Adam Shute ◽  
Arthur Wang ◽  
Derek M. McKay
Keyword(s):  
Immunological Memory ◽  
Hymenolepis Diminuta ◽  
Helminth Parasites ◽  
T Helper 2 ◽  
Memory Response ◽  
Adult Mice ◽  
Old Adult ◽  
Th2 Immunity ◽  
Helminth Therapy ◽  
Young Mice

Infection with helminth parasites reduces the severity of concomitant inflammatory disease in adult mice. There is an alarming increase of inflammatory bowel disease (IBD) in children. It is important to determine whether helminth therapy would be of value in pediatric IBD and whether triggering immunological memory to the worm would be anticolitic. Three-week-old (young) and eight-week-old (adult) Balb/c mice were infected with H. diminuta, and infectivity and T helper 2 (Th2) immunity were assessed. Other mice received H. diminuta with or without a crude worm extract ( HdE) 28–42 days postinfection (dpi) with or without dinitrobenzene sulphonic acid [DNBS, 1.5 mg (young) or 3 mg (adults), ir], and colitis was assessed 72 h later. Infected young mice developed Th2 immunity and expelled H. diminuta; expulsion was delayed by ~2 days compared with adult mice. Colitis, as gauged by macroscopic disease and histopathology scores, was less severe in young mice infected 10 days, but not 8 days, before DNBS. Protection against DNBS-induced colitis was accompanied by an increased capacity to make interleukin (IL)-4 and IL-10. Mice infected with H. diminuta were not protected from DNBS-colitis when challenged 28 days later; however, injection of these mice with HdE coincident with DNBS resulted in less disease and increased splenic IL-4 and IL-10. Using a boost (500 μg HdE, 28 dpi) and repeat HdE (100 μg, 42 dpi) regimen with infected mice suppressed DNBS-colitis, as did adoptive transfer of splenic CD4+ T cells from infected mice with low-dose HdE challenge. Should these data translate to IBD, then helminth therapy could be of value in pediatric-onset IBD, and defining the antigen(s) that elicit antihelminth immunological memory could serve as an anticolitic approach in previously infected individuals. NEW & NOTEWORTHY This study demonstrates that juvenile mice are protected from colitis by infection with the tapeworm Hymenolepis diminuta and that using worm antigen to trigger an immunological memory response in previously infected mice can be used to limit the severity of colitis.

Associations between gut microbiome, short chain fatty acids and blood pressure across ethnic groups: the HELIUS study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B Verhaar ◽  
D Collard ◽  
A Prodan ◽  
J.H.M Levels ◽  
A.H Zwinderman ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Fatty Acids ◽  
Ethnic Groups ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Funding Source ◽  
Microbiome Composition ◽  
Helius Study ◽  
Chain Fatty Acids

Abstract Background Gut microbiome composition is shaped by a combination of host genetic make-up and dietary habits. In addition, large ethnic differences exist in microbiome composition. Several studies in humans and animals have shown that differences in gut microbiota and its metabolites, including short chain fatty acids (SCFA), are associated with blood pressure (BP). We hypothesized that gut microbiome composition and its metabolites may be differently associated with BP across ethnic groups. Purpose To investigate associations of gut microbiome composition and fecal SCFA levels with BP across different ethnic groups. Methods We assessed the association between gut microbiome composition and office BP among 4672 subjects (mean age 49.8±11.7 years, 52%F) of 6 different ethnic groups participating in the HELIUS study. Gut microbiome composition was determined using 16S rRNA sequencing. Associations between microbiome composition and blood pressure were assessed using machine learning prediction models. The resulting best predictors were correlated with BP using Spearman's rank correlations. Fecal SCFA levels were measured with high-performance liquid chromatography in an age- and body mass index (BMI)-matched subgroup of 200 participants with either extreme low or high systolic BP. Differences in abundances of best predictors and fecal SCFA levels between high and low BP groups were assessed with Mann-Whitney U tests. Results Gut microbiome composition explained 4.4% of systolic BP variance. Best predictors for systolic BP included Roseburia spp. (ρ −0.15, p<0.001), Clostridium spp. (ρ −0.14, p<0.001), Romboutsia spp. (ρ −0.10, p<0.001), and Ruminococceae spp. (ρ −0.15, p<0.001) (Figure 1). Explained variance of the microbiome composition was highest in Dutch subjects (4.8%), but very low in African Surinamese, Ghanaian, and Turkish ethnic groups (ranging from 0–0.77%) Hence, we selected only participants with Dutch ethnicity for the matched subgroup. Participants with high BP had lower abundance of Roseburia hominis (p<0.01) and Roseburia spp. (p<0.05) compared to participants with low BP. However, fecal acetate (p<0.05) and propionate (p<0.01) levels were higher in participants with high BP. Conclusions In this cross-sectional study, gut microbiome composition was moderately associated with BP. Associations were strongly divergent between ethnic groups, with strongest associations in Dutch participants. Intriguingly, while Dutch participants with high BP had lower abundances of several SCFA-producing microbes, they had higher fecal SCFA levels. Intervention studies with SCFAs could provide more insight in the effects of these metabolites on BP. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): The Academic Medical Center (AMC) of Amsterdam and the Public Health Service of Amsterdam (GGD Amsterdam) provided core financial support for HELIUS. The HELIUS study is also funded by research grants of the Dutch Heart Foundation (Hartstichting; grant no. 2010T084), the Netherlands Organization for Health Research and Development (ZonMw; grant no. 200500003), the European Integration Fund (EIF; grant no. 2013EIF013) and the European Union (Seventh Framework Programme, FP-7; grant no. 278901).

scholarly journals Characterization of Ocular Surface Microbial Profiles Revealed Discrepancies between Conjunctival and Corneal Microbiota

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 405
Author(s):  
Anna Matysiak ◽  
Michal Kabza ◽  
Justyna A. Karolak ◽  
Marcelina M. Jaworska ◽  
Malgorzata Rydzanicz ◽  
...  
Keyword(s):  
Microbial Communities ◽  
Ocular Surface ◽  
Molecular Techniques ◽  
Corneal Tissue ◽  
Rna Seq ◽  
Microbiome Composition ◽  
Viral Sequences ◽  
Pcr Techniques ◽  
Unmapped Reads

The ocular microbiome composition has only been partially characterized. Here, we used RNA-sequencing (RNA-Seq) data to assess microbial diversity in human corneal tissue. Additionally, conjunctival swab samples were examined to characterize ocular surface microbiota. Short RNA-Seq reads, obtained from a previous transcriptome study of 50 corneal tissues, were mapped to the human reference genome GRCh38 to remove sequences of human origin. The unmapped reads were then used for taxonomic classification by comparing them with known bacterial, archaeal, and viral sequences from public databases. The components of microbial communities were identified and characterized using both conventional microbiology and polymerase chain reaction (PCR) techniques in 36 conjunctival swabs. The majority of ocular samples examined by conventional and molecular techniques showed very similar microbial taxonomic profiles, with most of the microorganisms being classified into Proteobacteria, Firmicutes, and Actinobacteria phyla. Only 50% of conjunctival samples exhibited bacterial growth. The PCR detection provided a broader overview of positive results for conjunctival materials. The RNA-Seq assessment revealed significant variability of the corneal microbial communities, including fastidious bacteria and viruses. The use of the combined techniques allowed for a comprehensive characterization of the eye microbiome’s elements, especially in aspects of microbiota diversity.

scholarly journals Importance of Intestinal Environment and Cellular Plasticity of Islets in the Development of Postpancreatectomy Diabetes

2021 ◽  
Author(s):  
Tatsuya Fukuda ◽  
Ryotaro Bouchi ◽  
Takato Takeuchi ◽  
Kikuko Amo-Shiinoki ◽  
Atsushi Kudo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Short Chain Fatty Acids ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Cellular Plasticity ◽  
Β Cell ◽  
Microbiome Composition ◽  
Significant Difference ◽  
Histological Characteristics ◽  
Design And Methods

<b>OBJECTIVE</b> <p>To elucidate the pathogenesis of post-pancreatectomy diabetes (PPDM).</p> <p><b>RESEARCH DESIGN AND METHODS</b></p> <p>Forty-eight patients without diabetes undergoing either pancreatoduodenectomy (PD) (n = 20) or distal pancreatectomy (DP) (n = 28) were included. 75-g oral glucose tolerance test was performed every 6 months. Microbiome composition and short-chain fatty acids in feces were examined before and 6 months after surgery. The association of histological characteristics of the resected pancreas with PPDM were examined.</p> <p><b>RESULTS</b></p> <p>During follow-up (median, 3.19 years), 2 out of 20 PD patients and 16 out of 28 DP patients developed PPDM. Proteobacteria relative abundance, plasma GLP-1, and fecal butyrate levels increased only after PD. Postsurgical butyrate levels were correlated with postsurgical GLP-1 levels. With no significant difference in the volume of the resected pancreas between the surgical procedures, both β-cell and α-cell areas in the resected pancreas were significantly higher in DP patients than in PD patients. In DP patients, the progressors to diabetes showed pre-existing insulin resistance compared with non-progressors, and both increased α- and β-cell areas were predictors of PPDM. Furthermore, in DP patients, α-cell and β-cell areas were associated with ALDH1A3 expression in islets.</p> <p><b>CONCLUSIONS</b></p> We postulate that a greater removal of β-cells contributes to the development of PPDM after DP. Islet expansion along with pre-existing insulin resistance is associated with high cellular-plasticity, which may predict the development of PPDM after DP. In contrast, PD is associated with alterations of gut microbiome and increases in SCFA production and GLP-1 secretion, possibly protecting against PPDM development.

scholarly journals Gut microbiome and its cofactors are linked to lipoprotein distribution profiles

2021 ◽  
Author(s):  
Josue Castro Mejia ◽  
Bekzod Khakimov ◽  
Mads Lind ◽  
Eva Garne ◽  
Petronela Paulova ◽  
...  
Keyword(s):  
Relative Abundance ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Future Research ◽  
Lipoprotein Subfractions ◽  
Lipoprotein Subclasses ◽  
Metagenome Sequencing ◽  
Lipoprotein Distribution ◽  
Host Characteristics

Increasing evidence indicates that the gut microbiome (GM) plays an important role in the etiology of dyslipidemia. To date, however, no in depth characterization of the associations between GM and its metabolic attributes with deep profiling of lipoproteins distributions (LPD) among healthy individuals has been conducted. To determine associations and contributions of GM composition and its cofactors with distribution profiles of lipoprotein subfractions, we studied blood plasma LPD, fecal short-chain fatty acids (SCFA) and GM of 262 healthy Danish subjects aged 19-89 years. Stratification of LPD segregated subjects into three clusters of profiles that reflected differences in the lipoprotein subclasses, corresponded well with limits of recommended levels of main lipoprotein fractions and were largely explained by host characteristics such as age and body mass index. Higher levels of HDL, particularly driven by large subfractions (HDL2a and HDL2b), were associated with a higher relative abundance of Ruminococcaceae and Christensenellaceae. Increasing levels of total cholesterol and LDL, which were primarily associated with large 1 and 2 subclasses, were positively associated with Lachnospiraceae and Coriobacteriaceae, and negatively with Bacteroidaceae and Bifidobacteriaceae. Metagenome sequencing showed a higher abundance of genes involved in the biosynthesis of multiple B-vitamins and SCFA metabolism among subjects with healthier LPD profiles. Metagenomic assembled genomes (MAGs) affiliated mainly to Eggerthellaceae and Clostridiales were identified as the contributors of these genes and whose relative abundance correlated positively with larger subfractions of HDL. The results of this study demonstrate that remarkable differences in composition and metabolic traits of the GM are associated with variations in LPD among healthy subjects. Findings from this study provide evidence for GM considerations in future research aiming to shade light on mechanisms of the GM - dyslipidemia axis.

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

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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