Akkermansia muciniphila Alleviates Dextran Sulfate Sodium (DSS)-Induced Acute Colitis by NLRP3 Activation

The gut microbiota and host immune response interaction influences the progression of intestinal inflammatory disease. As a well-recognized next-generation probiotic, Akkermansia muciniphila has been proved to play a crucial role in the progression of colitis, but its underlying mechanism remains inconclusive.

Slimy partners: the mucus barrier and gut microbiome in ulcerative colitis

Ulcerative colitis (UC) is a chronic recurrent intestinal inflammatory disease characterized by high incidence and young onset age. Recently, there have been some interesting findings in the pathogenesis of UC. The mucus barrier, which is composed of a mucin complex rich in O-glycosylation, not only provides nutrients and habitat for intestinal microbes but also orchestrates the taming of germs. In turn, the gut microbiota modulates the production and secretion of mucins and stratification of the mucus layers. Active bidirectional communication between the microbiota and its ‘slimy’ partner, the mucus barrier, seems to be a continually performed concerto, maintaining homeostasis of the gut ecological microenvironment. Any abnormalities may induce a disorder in the gut community, thereby causing inflammatory damage. Our review mainly focuses on the complicated communication between the mucus barrier and gut microbiome to explore a promising new avenue for UC therapy.

Survey on antibiotic regimens for necrotizing enterocolitis prescribed by Chinese pediatricians in 2020

BackgroundNecrotizing enterocolitis (NEC) is a serious intestinal inflammatory disease in neonates, and intravenous antibiotics constitute the main therapeutic strategy. Studies have shown that substantial variation in the selection of antibiotic regimens for NEC remains in many countries. The variability in antibiotic therapy selection in China is unclear.MethodsA cross-sectional study using an online questionnaire regarding antibiotic regimens for NEC was conducted among pediatricians working in tertiary hospitals in China.ResultsA total of 284 pediatricians from 29 provinces completed the survey; 37.9% of them administered one antibiotic, 56.7% administered two antibiotics and 2.4% administered three antibiotics. The top three single-antibiotic regimens for NEC were beta-lactamase inhibitors (n=66, 41.5%), carbapenems (n=46, 28.9%) and cephalosporins (n=33, 20.8%). Twenty combinations of two antibiotics were identified, and the top three combinations were beta-lactamase inhibitors and antianaerobic agents (n=49, 19.6%), carbapenems and glycopeptides (n=42, 16.8%), and cephalosporins and antianaerobic agents (n=37, 14.8%). Regarding the therapeutic duration of antibiotic treatment, 77.5% (n=220) of the pediatricians chose 5–10 days for stage II NEC, and 79.6% (n=226) chose 7–14 days for stage III NEC. Forty-three percent (n=122) of the respondents preferred to use carbapenems when NEC was diagnosed, and 83.3% (n=135) adjusted the antibiotics to carbapenems if a patient’s medical condition deteriorated or if the therapeutic efficacy was poor.ConclusionThis survey revealed that carbapenems were the most common antibiotics selected when NEC was diagnosed or a patient’s condition deteriorated, but the duration of the course of treatment for NEC varied substantially among doctors.

Nutrition and Lifestyle Factors Associated with Inflammatory Bowel Disease

Many dietary and lifestyle factors are found to be associated with the pathogenesis of IBD. The purpose of this study is to review the dietary and lifestyle factors associated with IBD. Several studies in IBD were discussed, and highlighted the independent effects of various dietary and lifestyle factors on the risk of IBD. IBD is chronic relapsing intestinal inflammatory disease characterized by complex interactions of multiple factors including smoking, major life stressors, diet and lifestyle. This paper attempts to investigate the association between dietary patterns and IBD risk and compare lifestyle factors among IBD patients. Dietary factors tend to play a pivotal role in the disease etiopathogenesis and course. However, research on food and IBD is contradictory. An excessive intake of sugar and animal fat is considered a risk factor for the development of IBD, whereas a high fiber diet and high intake of fruits and vegetables may play a protective effect. The role of lifestyle factors in IBD is crucial. Amply of evidence suggested that smoking is a causative agent in CD while it is protective against UC. Stress, depression, vitamin D deficiency and impaired sleep have all been all associated with incident IBD. A diet with a modified carbohydrate composition, a semi-vegetarian diet, a diet low in protein and fat and a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols should be taken into consideration for IBD patients.

The Role of Autophagy in Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is an idiopathic intestinal inflammatory disease, including ulcerative colitis (UC) and Crohn’s disease (CD). The abnormality of inflammatory and immune responses in the intestine contributes to the pathogenesis and progression of IBD. Autophagy is a vital catabolic process in cells. Recent studies report that autophagy is highly involved in various kinds of diseases, especially inflammation-related diseases, such as IBD. In this review, the biological characteristics of autophagy and its role in IBD will be described and discussed based on recent literature. In addition, several therapies for IBD through modulating the inflammasome and intestinal microbiota taking advantage of autophagy regulation will be introduced. We aim to bring new insight in the exploration of mechanisms for IBD and development of novel therapeutic strategies against IBD.

Interplay between Type 2 Transglutaminase (TG2), Gliadin Peptide 31-43 and Anti-TG2 Antibodies in Celiac Disease

Celiac disease (CD) is a common intestinal inflammatory disease involving both a genetic background and environmental triggers. The ingestion of gluten, a proteic component of several cereals, represents the main hexogen factor implied in CD onset that involves concomitant innate and adaptive immune responses to gluten. Immunogenicity of some gluten sequences are strongly enhanced as the consequence of the deamidation of specific glutamine residues by type 2 transglutaminase (TG2), a ubiquitous enzyme whose expression is up-regulated in the intestine of CD patients. A short gluten sequence resistant to intestinal proteases, the α-gliadin peptide 31-43, seems to modulate TG2 function in the gut; on the other hand, the enzyme can affect the biological activity of this peptide. In addition, an intense auto-immune response towards TG2 is a hallmark of CD. Auto-antibodies exert a range of biological effects on several cells, effects that in part overlap with those induced by peptide 31-43. In this review, we delineate a scenario in which TG2, anti-TG2 antibodies and peptide 31-43 closely relate to each other, thus synergistically participating in CD starting and progression.

Identification of Sero-Diagnostic Antigens for the Early Diagnosis of Johne’s Disease using MAP Protein Microarrays

Considerable effort has been directed toward controlling Johne’s disease (JD), a chronic granulomatous intestinal inflammatory disease caused by Mycobacterium avium subsp. paratuberculosis (MAP) in cattle and other ruminants. However, progress in controlling the spread of MAP infection has been impeded by the lack of reliable diagnostic tests that can identify animals early in the infection process and help break the transmission chain. To identify reliable antigens for early diagnosis of MAP infection, we constructed a MAP protein array with 868 purified recombinant MAP proteins, and screened a total of 180 well-characterized serum samples from cows assigned to 4 groups based on previous serological and fecal test results: negative low exposure (NL, n = 30); negative high exposure (NH, n = 30); fecal-positive, ELISA-negative (F + E−, n = 60); and both fecal- and ELISA-positive (F + E+, n = 60). The analyses identified a total of 49 candidate antigens in the NH, F + E−, and F + E+ with reactivity compared with the NL group (p < 0.01), a majority of which have not been previously identified. While some of the antigens were identified as reactive in only one of the groups, others showed reactivity in multiple groups, including NH (n = 28), F + E− (n = 26), and F + E+ (n = 17) groups. Using combinations of top reactive antigens in each group, the results reveal sensitivities of 60.0%, 73.3%, and 81.7% in the NH, F + E−, and F + E+, respectively at 90% specificity, suggesting that early detection of infection in animals may be possible and enable better opportunities to reduce within herd transmission that may be otherwise missed by traditional serological assays that are biased towards more heavily infected animals. Together, the results suggest that several of the novel candidate antigens identified in this study, particularly those that were reactive in the NH and F + E− groups, have potential utility for the early sero-diagnosis of MAP infection.

The Protective Influence of Chondroitin Sulfate, a Component of Human Milk, on Intestinal Bacterial Invasion and Translocation

Background:Human milk is known to be protective against necrotizing enterocolitis, a devastating intestinal inflammatory disease affecting the preterm population. Although the pathogenesis of necrotizing enterocolitis is yet to be solidified, intestinal integrity dysfunction, bacterial invasion and/or translocation, and inflammation may play important roles. Glycosaminoglycans, compounds naturally prevalent in both human milk and the intestine, are thought to be anti-inflammatory and capable of altering bacterial interactions within the gut.Research aim:In this study, we aimed to evaluate the potential of chondroitin sulfate, the most prominent class of glycosaminoglycans in human milk, to protect against bacterial infection in an intestinal in vitro model.Methods:T84 cell monolayers were treated with chondroitin sulfate and cell viability was assessed across a number of doses. Monolayers were then pretreated with chondroitin sulfate and subsequently challenged with E. coli invasion and translocation to evaluate any protective role of the compound against infection. Tight junction barrier function was assessed by transepithelial electrical resistance, and cytokine levels were evaluated.Results:Chondroitin sulfate at any dose up to 750 μg/ml was not associated with any statistically significant decrease in cell viability. Additionally, chondroitin sulfate at 750 μg/ml was associated with a 75% decrease in both bacterial invasion and translocation compared to control.Conclusions:These data suggest chondroitin sulfate may protect against bacterial infection through a reduction in both invasion and translocation, importantly without attendant reduction in cell viability.

Curcumin and Intestinal Inflammatory Diseases: Molecular Mechanisms of Protection

Intestinal inflammatory diseases, such as Crohn’s disease, ulcerative colitis, and necrotizing enterocolitis, are becoming increasingly prevalent. While knowledge of the pathogenesis of these related diseases is currently incomplete, each of these conditions is thought to involve a dysfunctional, or overstated, host immunological response to both bacteria and dietary antigens, resulting in unchecked intestinal inflammation and, often, alterations in the intestinal microbiome. This inflammation can result in an impaired intestinal barrier allowing for bacterial translocation, potentially resulting in systemic inflammation and, in severe cases, sepsis. Chronic inflammation of this nature, in the case of inflammatory bowel disease, can even spur cancer growth in the longer-term. Recent research has indicated certain natural products with anti-inflammatory properties, such as curcumin, can help tame the inflammation involved in intestinal inflammatory diseases, thus improving intestinal barrier function, and potentially, clinical outcomes. In this review, we explore the potential therapeutic properties of curcumin on intestinal inflammatory diseases, including its antimicrobial and immunomodulatory properties, as well as its potential to alter the intestinal microbiome. Curcumin may play a significant role in intestinal inflammatory disease treatment in the future, particularly as an adjuvant therapy.