scholarly journals Obesity-associated microbiota contributes to mucus layer defects in genetically obese mice

2020 ◽  
Vol 295 (46) ◽  
pp. 15712-15726
Author(s):  
Bjoern O. Schroeder ◽  
George M. H. Birchenough ◽  
Meenakshi Pradhan ◽  
Elisabeth E. L. Nyström ◽  
Marcus Henricsson ◽  
...  
Keyword(s):  
Growth Rate ◽  
Gut Microbiota ◽  
Metabolic Diseases ◽  
Intermediate Phenotype ◽  
Mucosal Barrier ◽  
Mucus Layer ◽  
Dietary Interventions ◽  
High Blood Glucose ◽  
Glucose Levels ◽  
Intestinal Mucus

The intestinal mucus layer is a physical barrier separating the tremendous number of gut bacteria from the host epithelium. Defects in the mucus layer have been linked to metabolic diseases, but previous studies predominantly investigated mucus function during high-caloric/low-fiber dietary interventions, thus making it difficult to separate effects mediated directly through diet quality from potential obesity-dependent effects. As such, we decided to examine mucus function in mouse models with metabolic disease to distinguish these factors. Here we show that, in contrast to their lean littermates, genetically obese (ob/ob) mice have a defective inner colonic mucus layer that is characterized by increased penetrability and a reduced mucus growth rate. Exploiting the coprophagic behavior of mice, we next co-housed ob/ob and lean mice to investigate if the gut microbiota contributed to these phenotypes. Co-housing rescued the defect of the mucus growth rate, whereas mucus penetrability displayed an intermediate phenotype in both mouse groups. Of note, non-obese diabetic mice with high blood glucose levels displayed a healthy colonic mucus barrier, indicating that the mucus defect is obesity- rather than glucose-mediated. Thus, our data suggest that the gut microbiota community of obesity-prone mice may regulate obesity-associated defects in the colonic mucosal barrier, even in the presence of dietary fiber.

scholarly journals Gut-Microbial Metabolites, Probiotics and Their Roles in Type 2 Diabetes

2021 ◽  
Vol 22 (23) ◽  
pp. 12846
Author(s):  
Lixiang Zhai ◽  
Jiayan Wu ◽  
Yan Y. Lam ◽  
Hiu Yee Kwan ◽  
Zhao-xiang Bian ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Amino Acids ◽  
Gut Microbiota ◽  
Aromatic Amino Acids ◽  
Microbial Metabolites ◽  
High Blood Glucose ◽  
Gaseous Products ◽  
Glucose Levels ◽  
Novel Therapeutic Strategies

Type 2 diabetes (T2D) is a worldwide prevalent metabolic disorder defined by high blood glucose levels due to insulin resistance (IR) and impaired insulin secretion. Understanding the mechanism of insulin action is of great importance to the continuing development of novel therapeutic strategies for the treatment of T2D. Disturbances of gut microbiota have been widely found in T2D patients and contribute to the development of IR. In the present article, we reviewed the pathological role of gut microbial metabolites including gaseous products, branched-chain amino acids (BCAAs) products, aromatic amino acids (AAAs) products, bile acids (BA) products, choline products and bacterial toxins in regulating insulin sensitivity in T2D. Following that, we summarized probiotics-based therapeutic strategy for the treatment of T2D with a focus on modulating gut microbiota in both animal and human studies. These results indicate that gut-microbial metabolites are involved in the pathogenesis of T2D and supplementation of probiotics could be beneficial to alleviate IR in T2D via modulation of gut microbiota.

OC.07.6 GELENTERUM AMELIORATES SEVERITY OF COLITIS IN DSS MURINE MODEL, WHILE MODULATING GUT MICROBIOTA AND INTESTINAL MUCUS LAYER

2013 ◽  
Vol 45 ◽  
pp. S72-S73
Author(s):  
F. Scaldaferri ◽  
L.R. Lopetuso ◽  
V. Petito ◽  
V. Gerardi ◽  
M. Bilotta ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Murine Model ◽  
Mucus Layer ◽  
Intestinal Mucus ◽  
Intestinal Mucus Layer

scholarly journals Gut Microbiota and Dietary Factors as Modulators of the Mucus Layer in Inflammatory Bowel Disease

2021 ◽  
Vol 22 (19) ◽  
pp. 10224
Author(s):  
Samuel Fernández-Tomé ◽  
Lorena Ortega Moreno ◽  
María Chaparro ◽  
Javier P. Gisbert
Keyword(s):  
Inflammatory Bowel Disease ◽  
Gut Microbiota ◽  
Bowel Disease ◽  
Dietary Factors ◽  
Host Immune System ◽  
Mucus Layer ◽  
Gut Health ◽  
Intestinal Mucus ◽  
Inflammatory Bowel ◽  
The Impact

The gastrointestinal tract is optimized to efficiently absorb nutrients and provide a competent barrier against a variety of lumen environmental compounds. Different regulatory mechanisms jointly collaborate to maintain intestinal homeostasis, but alterations in these mechanisms lead to a dysfunctional gastrointestinal barrier and are associated to several inflammatory conditions usually found in chronic pathologies such as inflammatory bowel disease (IBD). The gastrointestinal mucus, mostly composed of mucin glycoproteins, covers the epithelium and plays an essential role in digestive and barrier functions. However, its regulation is very dynamic and is still poorly understood. This review presents some aspects concerning the role of mucus in gut health and its alterations in IBD. In addition, the impact of gut microbiota and dietary compounds as environmental factors modulating the mucus layer is addressed. To date, studies have evidenced the impact of the three-way interplay between the microbiome, diet and the mucus layer on the gut barrier, host immune system and IBD. This review emphasizes the need to address current limitations on this topic, especially regarding the design of robust human trials and highlights the potential interest of improving our understanding of the regulation of the intestinal mucus barrier in IBD.

scholarly journals Host response to cholestyramine can be mediated by the gut microbiota

2020 ◽  
Author(s):  
Nolan K. Newman ◽  
Philip M. Monnier ◽  
Richard R. Rodrigues ◽  
Manoj Gurung ◽  
Stephany Vasquez-Perez ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Metabolic Diseases ◽  
Control Diet ◽  
Alpha Diversity ◽  
Mammalian Host ◽  
Beneficial Effects ◽  
Glucose Levels ◽  
Diet Induced Obesity ◽  
Expression Of Genes

AbstractThe gut microbiome has been implicated as a major factor contributing to metabolic diseases as well as being contributors to the response to drugs used for the treatment of such diseases. In this study, using a diet-induced obesity mouse model, we tested the effect of cholestyramine, a bile acid sequestrant, on the murine gut microbiome and mammalian metabolism. We also explored the hypothesis that some beneficial effects of this drug on systemic metabolism can be attributed to alterations in gut microbiota. First, we demonstrated that cholestyramine can decrease glucose and epidydimal fat levels. Next, while investigating gut microbiota we found increased alpha diversity of the gut microbiome of cholestyramine-treated mice, with fourteen taxa showing restoration of abundance to levels resembling those in mice fed with a control diet. Analyzing expression of genes known to be regulated by cholestyramine (including Cyp7a1), we confirmed the expected effect of this drug in the liver and ileum. Finally, using a transkingdom network analysis we inferred Acetatifactor muris and Muribaculum intestinale as potential mediators/modifiers of cholestyramine effects on the mammalian host. In addition, A. muris correlated positively with glucagon (Gcg) expression in the ileum and negatively correlated with small heterodimer partner (Shp) expression in the liver. Interestingly, A. muris also correlated negatively with glucose levels, further indicating the potential probiotic role for A. muris. In conclusion, our results indicate the gut microbiome has a role in the beneficial effects of cholestyramine and suggest specific microbes as targets of future investigations.

scholarly journals Fecal microbiota transplantation reconstructs the gut microbiota of septic mice and protects the intestinal mucosal barrier

2020 ◽  
Author(s):  
Xiaowei Gai ◽  
Huawei Wang ◽  
Yaqing Li ◽  
Haotian Zhao ◽  
Cong He ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Gut Microbiota ◽  
Tight Junction ◽  
Short Chain Fatty Acid ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Chain Fatty Acid ◽  
Mucosal Barrier ◽  
Mucus Layer ◽  
Intestinal Mucosal Barrier

AbstractThe gastrointestinal (GI) tract has long been hypothesized to play an integral role in the pathophysiology of sepsis, and gut microbiota (GM) dysbiosis may be the key factor. Previous studies has confirmed that microbiome is markedly altered in critical illness. We aimed to confirm the existence of gut microbiota imbalance in the early stage of sepsis, observe the effect of fecal microbiota transplantation (FMT) on sepsis, and explore whether FMT can reconstruct the GM of septic mice and restore its protective function on the intestinal mucosal barrier. Through the study of flora, mucus layer, tight junction, immune barrier, and short-chain fatty acid changes in septic mice and fecal microbiota transplanted mice, we found that GM imbalance exists early in sepsis. FMT can improve morbidity and effectively reduce mortality in septic mice. After the fecal bacteria were transplanted, the abundance and diversity of the gut flora were restored, and the microbial characteristics of the donors changed. FMT can effectively reduce epithelial cell apoptosis, improve the composition of the mucus layer, upregulate the expression of tight junction proteins, and reduce intestinal permeability and the inflammatory response, thus protecting the intestinal barrier function. After FMT, Lachnospiraceae contributes the most to intestinal protection through enhancement of the L-lysine fermentation pathway, resulting in the production of acetate and butanoate, and may be the key bacteria for short-chain fatty acid metabolism and FMT success.

scholarly journals Fecal microbiota transplantation reconstructs the gut microbiota of septic mice and protects the intestinal mucosal barrier

2020 ◽  
Author(s):  
Xiaowei Gai ◽  
Huawei Wang ◽  
Yaqing Li ◽  
Haotian Zhao ◽  
Cong He ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Sham Group ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Mucosal Barrier ◽  
Intragastric Administration ◽  
Mucus Layer ◽  
Gut Flora ◽  
Protective Function ◽  
Intestinal Mucosal Barrier

Abstract Background This study aimed to confirm the existence of gut microbiota (GM) imbalance in the early stage of sepsis, observe the effect of fecal microbiota transplantation (FMT) on sepsis, and explore whether FMT can reconstruct the GM of septic mice and restore its protective function on the intestinal mucosal barrier. Methods The study included acute experiments and 7-day mortality observation experiments with clean-grade C57BL/6, and they were randomly divided randomly into three groups, namely, the sham group, the sepsis model group and the fecal microbiota transplantation group. Fresh feces from 10 mice were kept every day to make fecal liquid. The Sham group and the CLP group were given intragastric administration once a day with phosphate-buffered saline, and the FMT group mice were given fecal microbiota transplantation once a day. The animals were euthanized at 12, 24, and 48 h after modeling, and blood, colon, and stool from each mouse were collected at the same time.Results Colonic pathological scores, pro-inflammatory cytokines, TLR4/MyD88/NF-κB protein levels, and gene expression levels, were lower in the FMT group, while anti-inflammatory factors, mucus layer thickness, MUC2, occludin, and ZO-1 proteins were higher in the FMT group than the CLP group. Bacterial flora analysis showed gut flora was reconstructed after FMT. The species composition of the differential pathways revealed that the Lachnospiraceae group contributed the most by the L-lysine pathway of fermentation to acetate and butanoate.Conclusion GM imbalance exists early in sepsis. FMT can improve morbidity and effectively reduce mortality in septic mice. After the fecal bacteria were transplanted, the abundance and diversity of the gut flora were restored, and the microbial characteristics of the donors changed. FMT can effectively reduce epithelial cell apoptosis, improve the composition of the mucus layer, upregulate the expression of tight junction proteins, and reduce intestinal permeability and the inflammatory response, thus protecting the intestinal barrier function. After FMT, Lachnospiraceae contributes the most to intestinal protection through enhancement of the L-lysine fermentation pathway, resulting in the production of acetate and butanoate, and may be the key bacteria for short-chain fatty acid metabolism and FMT success.

scholarly journals Initiation of Pancreatic Cancer: The Interplay of Hyperglycemia and Macrophages Promotes the Acquisition of Malignancy-Associated Properties in Pancreatic Ductal Epithelial Cells

2021 ◽  
Vol 22 (10) ◽  
pp. 5086
Author(s):  
Lilli Otto ◽  
Sascha Rahn ◽  
Tina Daunke ◽  
Frederik Walter ◽  
Elsa Winter ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Metabolic Diseases ◽  
Immune Cell ◽  
Epithelial Mesenchymal Transition ◽  
Ductal Adenocarcinoma ◽  
Immune Cell Population ◽  
High Blood Glucose ◽  
Mesenchymal Transition ◽  
Glucose Levels ◽  
Tnf Α

Pancreatic ductal adenocarcinoma (PDAC) is still one of the most aggressive solid malignancies with a poor prognosis. Obesity and type 2 diabetes mellitus (T2DM) are two major risk factors linked to the development and progression of PDAC, both often characterized by high blood glucose levels. Macrophages represent the main immune cell population in PDAC contributing to PDAC development. It has already been shown that pancreatic ductal epithelial cells (PDEC) undergo epithelial–mesenchymal transition (EMT) when exposed to hyperglycemia or macrophages. Thus, this study aimed to investigate whether concomitant exposure to hyperglycemia and macrophages aggravates EMT-associated alterations in PDEC. Exposure to macrophages and elevated glucose levels (25 mM glucose) impacted gene expression of EMT inducers such as IL-6 and TNF-α as well as EMT transcription factors in benign (H6c7-pBp) and premalignant (H6c7-kras) PDEC. Most strikingly, exposure to hyperglycemic coculture with macrophages promoted downregulation of the epithelial marker E-cadherin, which was associated with an elevated migratory potential of PDEC. While blocking IL-6 activity by tocilizumab only partially reverted the EMT phenotype in H6c7-kras cells, neutralization of TNF-α by etanercept was able to clearly impair EMT-associated properties in premalignant PDEC. Altogether, the current study attributes a role to a T2DM-related hyperglycemic, inflammatory micromilieu in the acquisition of malignancy-associated alterations in premalignant PDEC, thus providing new insights on how metabolic diseases might promote PDAC initiation.

scholarly journals EFFECT OF VAMAN IN STHUL MADHUMEHA: A CASE STUDY

2020 ◽  
Vol 11 (10) ◽  
pp. 12-16
Author(s):  
Sushil V Chawre ◽  
Sneha S Kamre ◽  
Prakash R Kabra
Keyword(s):  
Metabolic Diseases ◽  
Cost Effective ◽  
Long Term Effects ◽  
High Blood Glucose ◽  
Progressive Development ◽  
Glucose Levels ◽  
Ayurvedic Drugs ◽  
Long Term Effect

The study was conducted to evaluate cost effective and convenient treatment for Sthul Madhumeha in Ayurved. Diabetes is a group of metabolic diseases in which there are high blood glucose levels over a prolonged period. This high blood sugar produces the symptoms of frequent urination, increased thirst and increased hunger. Long term effect of Diabetes includes damage, dysfunction and failure of various organs. The long-term effects include progressive development of vasculopathy that may lead to renal failure, neuropathy etc. Prevalence of diabetes increased with age and reached at peaked at 60 to 69 years of age followed by declined at 70 years of age in India subjects. Ayurveda describes Prameha as a disease having cardinal features of “Prabhuta Avilamutrata’ which means excessive quantity and increased frequency of urine having turbid appearance. Ancient texts like Charak Samhita, Sushruta Samhita etc accepted that there are twenty types of Prameha according to Dosha. Charak has explained two different lines of treatment for both Sthula-pramehi and Krisha-pramehi types. Brihan to the Krish Pramehi and Apatarpana in the form of Shodhan and Shamana. The study was carried out to see the effect of Vaman Karma in the management of Prameha. To Study the effect of Vaman Karma in Prameha. A case study of 45 years old male patient with Adhaman, Udar-daha, Amlodgar, Katishula since 4-5 years, was treated with Vaman Karma followed by Ayurvedic drugs. A case recorded and treated in our institute. Significant results were seen in patient. Encouraging results were obtained which are presented in full paper.

scholarly journals EXPLORING CO-INFECTIONS IN THE GASTROINTESTINAL TRACT: DISSECTING THE INTERACTION BETWEEN FUSOBACTERIUM NUCLEATUM AND CLOSTRIDIODES DIFFICILE

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S40-S40
Author(s):  
Melinda Engevik ◽  
Heather Danhof ◽  
Jennifer Auchtung ◽  
Maribeth Nicholson ◽  
Qinglong Wu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Biofilm Formation ◽  
Fusobacterium Nucleatum ◽  
Extracellular Polysaccharide ◽  
Mucus Layer ◽  
Healthy Human ◽  
Associated Bacteria ◽  
Intestinal Mucus ◽  
Clostridioides Difficile ◽  
Intestinal Mucus Layer

Abstract Background Clostridioides difficile is a common healthcare associated pathogen in U.S. hospitals, incurring billions of dollars in treatment costs each year. Microbiome analysis of C. difficile infected (CDI) patients have revealed alterations of the gut microbiota. It has been speculated that select members of this altered microbiota may influence C. difficile pathogenesis. C. difficile is known to reside in the intestinal mucus layer, but at present the interactions between C. difficile and other mucus-associated bacteria are poorly defined. To address these gaps in knowledge, we have focused on an entirely human-centered approach, employing human-derived MUC2, fecal bioreactors and patient samples. We hypothesized that select mucus-associated bacteria would promote C. difficile colonization and biofilm formation. Methods & Results To create a model of the human intestinal mucus layer and gut microbiota, we developed a bioreactor system with human MUC2-coated coverslips. Bioreactors were inoculated with healthy human feces, treated with clindamycin and infected with C. difficile to mimic CDI. C. difficile was found to colonize and form biofilms on MUC2-coated coverslips and 16S rRNA sequencing revealed a unique biofilm profile with substantial co-colonization with Fusobacterium. Consistent with our bioreactor data, publicly available datasets and patient stool samples revealed that a subset of patients with C. difficile infection harbored high levels of F. nucleatum OTUs. We also isolated microbes from adult patients and pediatric IBD patient stool who were positive for C. difficile and F. nucleatum and identified co-localization between these strains. RNAseq data revealed significant changes in C. difficile chemotaxis and surface adhesion genes following exposure to F. nucleatum metabolites. C. difficile was found to co-aggregate with F. nucleatum; an effect that was inhibited by blocking the Fusobacterial adhesin RadD and C. difficile flagella. Moreover, a ΔradD mutant of F. nucleatum lost the ability to aggregate with C. difficile. Conversely, removal of flagella from C. difficile significantly reduced the interaction between WT F. nucleatum and C. difficile. Addition of F. nucleatum also enhanced C. difficile biofilm formation, increasing the levels extracellular polysaccharide. Conclusions Collectively, these data demonstrate the unique role of mucus-associated bacteria such as F. nucleatum in facilitating colonization of the mucus layer by pathogenic C. difficile.

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