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Background: The possibility of preventing inflammatory bowel disease (IBD) is becoming more plausible due to advances in understanding preclinical disease and successful prevention trials in other immune-mediated diseases, such as type 1 diabetes and rheumatoid arthritis. However, before that possibility becomes reality, several efforts need to occur in parallel and in a coordinated way., Aim: To propose some critical steps necessary for advancing the field of IBD prediction and prevention., Methods: We reviewed the current literature to identify the necessary steps toward a preventive strategy for IBD., Results: The first step should determine the most robust predictive biomarkers and validate them across independent cohorts, creating a multidimensional predictive tool. The second step is to gain a better understanding of the preferences of first-degree relatives and people at risk for IBD, informing the implementation of screening and preventive strategies. Third, these efforts should contribute to the development of high-risk clinics and establish the necessary networks for disease prevention trials., Conclusions: Advancing the field of IBD prediction and prevention will require a multifaceted approach, integrating biomarker discovery, understanding patient preferences, and establishing infrastructure for a collaborative network to support the practical implementation of IBD prevention strategies., (© 2024 John Wiley & Sons Ltd.)

Background and Aims: Modifiable risk factors in inflammatory bowel disease [IBD], such as physical activity, may be used as prevention strategies. However, the findings of previous studies on the association between physical activity and IBD risk have been inconsistent. We aimed to perform a systematic review and meta-analysis to estimate the effect of physical activity on IBD risk., Methods: A search was conducted for relevant studies published before April 2023 that assessed the effect of pre-IBD diagnosis levels of physical activity on IBD incidence. Individual summary statistics [relative risks; RR], and confidence intervals [CI] were extracted with forest plots generated. We used the Grading of Recommendations Assessment, Development and Evaluation [GRADE] approach to assess the quality of evidence., Results: Ten observational studies were included. For cohort studies, there were 1182 Crohn's disease [CD] and 2361 ulcerative colitis [UC] patients, with 860 992 participants without IBD. For case-control studies, there were 781 CD to 2636 controls, and 1127 UC to 3752 controls. Compared with individuals with low physical activity levels, the RRs of CD in individuals with high physical activity levels for cohort and case-control studies were 0.78 [95% CI 0.68-0.88, p = 0.0001] and 0.87 [95% CI 0.79-0.95, p = 0.003], respectively. For UC, the RRs were 0.62 [95% CI 0.43-0.88, p = 0.008] and 0.74 [95% CI 0.51-1.07, p = 0.11]., Conclusion: This meta-analysis suggests that physical activity is inversely associated with the risk of developing IBD, more so in CD than in UC., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction and Objective: Both periodontitis and non-specific bowel diseases (IBD) are complex chronic diseases, and the elements connecting them are the dysregulated microbiota and abnormal immune response of the host. In turn, in the etiology of these diseases, the common environmental risk factor is improper mode of nutrition. The aim of the study is to review nutritional interventions and effective nutritional protocols applied in periodontitis and IBD. The result of the review will be identification of dietary recommendations exerting a beneficial effect on the reduction of the risk of development and alleviation of the severity of both diseases. At the same time, non-recommended dietary choices will be indicated., Review Methods: A review of literature was carried out using the databases PubMed, Google Scholar, and Web of Science. Publications were analyzed by a non-systematic literature review aimed at making a brief synthesis of the collected information., Brief Description of the State of Knowledge: Diets recommended to patients with both periodontitis and IBD included the Mediterranean diet, DASH diet and vegetarian diet; excluding veganism, raw foodism and fruitarianism. For patients with IBD, special dietary recommendations were elaborated on the recommendations of the International Organization for Research into Inflammatory Bowel Diseases (IOIBD), and specific diets, i.e. specific carbohydrate diet (SCD), and Groningen anti-inflammatory diet (GrAID). In the process of treatment of oral and intestinal dysbiosis, probiotic therapy is beneficial in both diseases, specified as the Western diet. Non-conventional diets are not recommended., Summary: Diet therapy for inflammatory periodontal diseases and IBD requires extensive individualization; nevertheless, a universal principle is avoidance of highly processed food, and implementation of easily digestible meals based on natural, ecological products. Proper nutrition plays a crucial role in primary prevention of both diseases analyzed, whereas in secondary prevention, diet therapy is a valuable supplementation of pharmacotherapy.

The epithelium lining the intestinal tract serves a multifaceted role. It plays a crucial role in nutrient absorption and immune regulation and also acts as a protective barrier, separating underlying tissues from the gut lumen content. Disruptions in the delicate balance of the gut epithelium trigger inflammatory responses, aggravate conditions such as inflammatory bowel disease, and potentially lead to more severe complications such as colorectal cancer. Maintaining intestinal epithelial homeostasis is vital for overall health, and there is growing interest in identifying nutraceuticals that can strengthen the intestinal epithelium. α-Ketoglutarate, a metabolite of the tricarboxylic acid cycle, displays a variety of bioactive effects, including functioning as an antioxidant, a necessary cofactor for epigenetic modification, and exerting anti-inflammatory effects. This article presents a comprehensive overview of studies investigating the potential of α-ketoglutarate supplementation in preventing dysfunction of the intestinal epithelium., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: ANA has served on the scientific advisory board for Geneoscopy.

The early-life period is one of microbiome establishment and immune maturation. Early-life exposures are increasingly being recognised to play an important role in IBD risk. The composition of functions of the gut microbiome in the prenatal, perinatal, and postnatal period may be crucial towards development of health or disease, including IBD, later in life. We herein present a comprehensive summary of the interplay between early-life factors and microbiome perturbations, and their association with risk of IBD. In addition, we provide an overview of host and external factors in early life that are known to impact gut microbiome maturation and exposures implicated in IBD risk. Considering the emerging concept of IBD prevention, we propose strategies to minimise maternal and offspring exposure to potentially harmful variables and recommend protective measures during pregnancy and the postpartum period. This holistic view of early-life factors and microbiome signatures among mothers and their offspring will help frame our current understanding of their importance towards IBD pathogenesis and frame the roadmap for preventive strategies., Competing Interests: Competing interests: MA has served as a consultant for Douglas Pharmacoceuticals. LZ and SCN are named inventors of patent applications held by the CUHK and MagIC that cover the therapeutic and diagnostic use of microbiome. SCN has served as an advisory board member for Pfizer, Ferring, Janssen, and Abbvie and received honoraria as a speaker for Ferring, Tillotts, Menarini, Janssen, Abbvie, and Takeda. SCN has received research grants through her affiliated institutions from Olympus, Ferring, and Abbvie. SCN is a founder member, non-executive director, non-executive scientific advisor, and shareholder of GenieBiome Ltd. SCN receives patent royalties through her affiliated institutions. TJ has served as a consultant for Ferring., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The incidence of chronic inflammatory diseases (CIDs) is dramatically increasing in the developed world, resulting in an increased burden of disease in childhood. Currently, there are limited effective strategies for treating or preventing these conditions. To date, myriads of cross-sectional studies have described alterations in the composition of the gut microbiota in a variety of disease states, after the disease has already occurred. We suggest that to mechanically link these microbiome changes with disease pathogenesis, a prospective cohort design is needed to capture changes that precede or coincide with disease onset and symptoms. In addition, these prospective studies must integrate microbiological, metagenomic, meta transcriptomic and metabolomic data with minimal and standardized clinical and environmental metadata that allow to correctly compare and interpret the results of the analysis of the human microbiota in order to build a system-level model of the interactions between the host and the development of the disease. The creation of new biological computational models thus constructed will allow us to finally move from the detection of simple elements of "association" to the identification of elements of real "causality" allowing to provide a mechanistic approach to the exploration of the development of CIDs.This can only be done when these diseases are studied as complex biological networks. In this chapter we discuss the current knowledge regarding the contribution of the microbiome to CID in childhood, focusing on celiac disease and inflammatory bowel disease, with the overall aim of identifying pathways to shift research from descriptive to mechanistic approaches. We then examine how some components of the microbiota, through epigenetic reprogramming, can start the march from genetic predisposition to clinical expression of CIDs, thus opening up new possibilities for intervention, through microbiota therapy targeting the manipulation of the composition and function of the microbiota, for future applications of precision medicine and primary prevention., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

The first 1000 days of life is a critical period that contributes significantly to the programming of an individual's future health. Among the many changes that occur during this period early in life, there is growing evidence that the establishment of healthy gut microbiota plays an important role in the prevention of both short- and long-term health problems. Numerous publications suggest that the quality of the gut microbiota colonisation depends on several dietary factors, including breastfeeding. In this respect, a relationship between breastfeeding and the risk of inflammatory bowel disease (IBD) has been suggested. IBDs are chronic intestinal diseases, and perinatal factors may be partly responsible for their onset. We review the existence of links between breastfeeding and IBD based on experimental and clinical studies. Overall, despite encouraging experimental data in rodents, the association between breastfeeding and the development of IBD remains controversial in humans, partly due to the considerable heterogeneity between clinical studies. The duration of exclusive breastfeeding is probably decisive for its lasting effect on IBD. Thus, specific improvements in our knowledge could support dietary interventions targeting the gut microbiome, such as the early use of prebiotics, probiotics or postbiotics, in order to prevent the disease.

The oral cholera vaccine WC-rBS consists of 4 different inactivated strains of Vibrio cholerae (LPS source) admixed with recombinant cholera toxin B subunit. Because of its unique composition and anti-inflammatory properties reported for both CTB and low doses of LPS from other Gram-negative bacteria, we speculated that WC-rBS might have anti-inflammatory potential in a chronic autoimmune disease such as inflammatory bowel diseases. First in vitro endotoxin tolerance experiments showed the surprising WC-rBS potential in the modulation of inflammatory responses on both PBMCs and THP1 cells. WC-rBS was further evaluated in the Dextran Sodium Sulfate colitis mouse model. Administrated orally at different dosages, WC-rBS vaccine was safe and showed immunomodulatory properties when administered in a preventive mode (before and during the induction of DSS colitis) as well as in a curative mode (after colitis induction); with improvement of disease activity index (from 27 to 73%) and histological score (from 65 to 88%). Interestingly, the highest therapeutic effect of WC-rBS vaccine was observed with the lowest dosage, showing even better anti-inflammatory properties than mesalamine; an approved 5-aminosalicylic acid drug for treating IBD patients. In summary, this is the first time that a prophylactic medicine, safe and approved for prevention of an infectious disease, showed a benefit in an inflammatory bowel disease model, potentially offering a novel therapeutic modality for IBD patients., Competing Interests: Marine Meunier, Adrian Spillmann, Klaus Schwamborn and Melissa Hanson were all employees of the Valneva group when the work was done. The Swedish subsidiary of the Valneva group owns Dukoral®, i.e. the WC-rBS vaccine. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Meunier et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The increasing incidence of inflammatory bowel disease (IBD: Crohn's disease and ulcerative colitis) around the world has coincided with a wide array of environmental and epidemiologic changes. The relationship between IBD incidence and household or family size decline, however, has not been examined before. Our background epidemiological analyses suggested an inverse association between household size and IBD incidence. We aimed to examine this further in a murine model., Methods: We designed a unique two-generation cohousing model of family size and IBD susceptibility in C57BL/6J mice. Serial fecal microbiomes during cohousing were examined by high-throughput 16S rRNA sequencing. After cohousing for 10 days, mice were exposed to dextran sulfate sodium (DSS) to induce acute colitis. Body weight as a significant correlate of colitis severity was measured., Results: Mice in a large household arrangement demonstrated less weight loss than mice in the small household arrangement in the DSS model. Age- and housing-dependent microbiome shifts were found., Conclusions: Larger households may be protective against intestinal inflammation through intergenerational microbiome modulation. Our observations may set the foundation for age-dependent, microbiome-directed future prevention against IBD., Impact: Epidemiological analyses in this study suggested that IBD incidence may inversely correlate with household size (an indicator of family size/children per family), which has not been examined before. A uniquely designed two-generation cohousing model of family size and IBD susceptibility in mice supported our epidemiologic observations. Microbiome changes in our cohousing model may set the foundation for age-dependent, microbiome-directed prevention against IBD., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

The prevalence of inflammatory bowel disease (IBD) is increasing, which is concerning because IBD is a known risk factor for the development of colorectal cancer. Emerging evidence highlights environmental factors, particularly dietary factors and gut microbiota dysbiosis, as pivotal inducers of IBD onset. Goji berry, an ancient tonic food and a nutraceutical supplement, contains a range of phytochemicals such as polysaccharides, carotenoids, and polyphenols. Among these phytochemicals, L. barbarum polysaccharides (LBPs) are the most important functional constituents, which have protective effects against oxidative stress, inflammation, and neurodegeneration. Recently, the beneficial effects of goji berry and associated LBPs consumption were linked to prebiotic effects, which can prevent dysbiosis associated with IBD. This review assessed pertinent literature on the protective effects of goji berry against IBD focusing on the gut microbiota and their metabolites in mediating the observed beneficial effects.

Inflammatory bowel disease (IBD) is a group of diseases with a chronic course, characterized by periods of exacerbation and remission. One of the elements that could potentially predispose to IBD is, among others, a low-fiber diet. Dietary fiber has many functions in the human body. One of the most important is its influence on the composition of the intestinal microflora. Intestinal dysbiosis, as well as chronic inflammation that occurs, are hallmarks of IBD. Individual components of dietary fiber, such as β-glucan, pectin, starch, inulin, fructooligosaccharides, or hemicellulose, can significantly affect preventive effects in IBD by modulating the composition of the intestinal microbiota or sealing the intestinal barrier, among other things. The main objective of the review is to provide information on the effects of individual fiber components of the diet on the risk of IBD, including, among other things, altering the composition of the intestinal microbiota.

Inflammatory bowel disease (IBD) is a group of intestinal disorders, of unknown etiology, characterized by chronic inflammation within the gut. They are gradually becoming critical because of the increasing incidence worldwide and improved diagnosis. Due to the important side effects observed during conventional therapy, natural bioactive components are now under intense investigation for the prevention and treatment of chronic illnesses. The Brassicaceae family comprises vegetables widely consumed all over the world. In recent decades, a growing body of literature has reported that extracts from the Brassicaceae family and their purified constituents have anti-inflammatory properties, which has generated interest from both the scientific community and clinicians. In this review, data from the literature are scrutinized and concisely presented demonstrating that Brassicaceae may have anti-IBD potential. The excellent biological activities of Brassicacea are widely attributable to their ability to regulate the levels of inflammatory and oxidant mediators, as well as their capacity for immunomodulatory regulation, maintenance of intestinal barrier integrity and intestinal flora balance. Possible future applications of bioactive-derived compounds from Brassicaceae for promoting intestinal health should be investigated.

There has been a substantial rise in the incidence and prevalence of clinical patients presenting with inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis. Accumulating evidence has corroborated the view that dietary factors (particularly diets with high levels of saturated fat or sugar) are involved in the development and progression of IBD, which is predominately associated with changes in the composition of the gut microbiota and an increase in the generation of reactive oxygen species. Notably, the ecological imbalance of the gut microbiome exacerbates oxidative stress and inflammatory responses, leading to perturbations of the intestinal redox balance and immunity, as well as mucosal integrity. Recent findings have revealed that functional amino acids, including L-glutamine, glycine, L-arginine, L-histidine, L-tryptophan, and hydroxyproline, are effectively implicated in the maintenance of intestinal redox and immune homeostasis. These amino acids and their metabolites have oxygen free-radical scavenging and inflammation-relieving properties, and they participate in modulation of the microbial community and the metabolites in the gut. The principal focus of this article is a review of recent advances in the oxidative pathomechanisms of IBD development and progression in relation to dietary factors, with a particular emphasis on the redox and signal transduction mechanisms of host cells in response to unbalanced diets and enterobacteria. In addition, an update on current understanding of the protective effects of functional amino acids against IBD, together with the underlying mechanisms for this protection, have been provided., (© The Author(s) 2022. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Inflammatory bowel disease has become a global health problem at the turn of the 21st century. The pathogenesis of this disorder has not been fully explained. In addition to non-modifiable genetic factors, a number of modifiable factors such as diet or gut microbiota have been identified. In this paper, the authors focus on the role of nutrition in the prevention of inflammatory bowel disease as well as on the available options to induce disease remission by means of dietary interventions such as exclusive and partial enteral nutrition in Crohn's disease, the efficacy of which is reported to be comparable to that of steroid therapy. Diet is also important in patients with inflammatory bowel disease in the remission stage, during which some patients report irritable bowel disease-like symptoms. In these patients, the effectiveness of diets restricting the intake of oligo-, di-, monosaccharides, and polyols is reported.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease with relapses and periods of remission. Forasmuch as, dysregulation of the immune system is one of the triggers of IBD, taking probiotics as one of the immunomodulators in the gut, could help to control inflammation and IBD via influencing signalling pathways. Here, we aimed to investigate the efficacy of five selected Bifidobacterium strains in modulating JAK/STAT and NF-kB inflammatory signalling pathways via using the in vitro assay. A quantitative real-time polymerase chain reaction assay was used to analyse the expression of JAK/STAT and inflammatory genes followed by potential probiotic treatments before, after and simultaneously with the inflammation induction (sonicated pathogen). The production of IL-6 and IL-1β after probiotic treatment was evaluated. Probiotic treatment resulted in the downregulation of TIRAP, IRAK4, NEMO and RIP genes in the NF-kB pathway, as well as JAK genes compared to sonicate-treated cells. The expression of STAT genes was different after our selected Bifidobacterium strains treatment. The production of IL-6 and IL-1β decreased after probiotic treatment. These strains of Bifidobacterium spp. showed anti-inflammatory effects on HT-29 cells via modulation of JAK/STAT and NF-kB signalling pathways. The use of Bifidobacterium spp. could be considered as a suitable preventive and complementary treatment for patients with inflammatory bowel disease., (© 2022 Society for Applied Microbiology.)

Vitamin D is essential for the regulation of the immune system. In recent years, the role of vitamin D in the control of several autoimmune conditions such as inflammatory bowel disease (IBD), celiac disease, type 1 diabetes mellitus (T1DM), and others has been investigated. The aim of this review was to define the level of knowledge on vitamin D's role in these disorders, as well as the preventive and therapeutic role of vitamin D supplementation. Relevant studies published over the last 20 years were identified via a PubMed/Medline (http://www.ncbi.nlm.nih.gov/pubmed/) search using the keywords: vitamin D, autoimmune disease, and prevention. Vitamin D deficiency or impaired function of the enzymes necessary for its activity has been shown to affect the onset and severity of the autoimmune diseases examined. Vitamin D supplementation appears useful in the support therapy of IBD. Its role in celiac disease, autoimmune hepatitis, T1DM, and autoimmune thyroiditis is unclear. In conclusion, further studies are needed to define whether vitamin D is a cause or a result of the most common autoimmune, extra-skeletal diseases, such as IBD. Vitamin D should be provided to all newborns during their first year of life. Afterwards, the vitamin D supplementation regimen should be tailored to the presence of risk factors for vitamin D deficiency and/or specific disease., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s). Published by IMR Press.)

Background: The cardioprotective diet was reported to be associated with several chronic cardiometabolic diseases through an anti-inflammation effect. However, the association between the cardioprotective diet and the risk of inflammatory bowel disease (IBD) was unclear and deserved to be further explored. Methods: We calculated the cardioprotective diet score based on the consumptions of seven common food groups using the validated food frequency questionnaire data in the UK Biobank. Incident IBD was ascertained from primary care data, inpatient data, and the death registry. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between the cardioprotective diet score and the risk of IBD. Results: During a mean follow-up of 12.1 years, we documented 2717 incident IBD cases, including 851 cases of Crohn’s disease and 1866 cases of ulcerative colitis. Compared to participants with a cardioprotective diet score of 0−1, we observed a decreased risk of IBD among participants with cardioprotective diet scores of 3 (HR 0.85, 95% CI 0.73−0.99), 4 (HR 0.84, 95% CI 0.72−0.98), and 5−7 (HR 0.77, 95% CI 0.66−0.89) (p-trend < 0.001). Conclusions: A greater adherence to the cardioprotective diet was associated with a lower risk of IBD. Our finding highlighted the importance of focusing on the cardioprotective diet to prevent IBD., Competing Interests: The authors declare that they have no conflict of interest.

The occurrence of inflammatory bowel disease (IBD) is related to environmental factors, host immune status, genetic susceptibility and flora imbalance. With the development of sequencing technologies, the relationship between intestinal microbiota and IBD has been further studied and confirmed in many aspects. This article summarizes the characteristics of microbiota alterations in patients with IBD, as well as the role and mechanisms of microbiota dysbiosis in the onset and development of IBD, and discusses the research status of therapies based on intestinal microbiota, prospecting the future of intestinal flora in the prevention, diagnosis, treatment and prognosis of IBD.

Inflammatory bowel disease (IBD) describes a heterogenous group of diseases characterized by chronic inflammation of the intestinal tract. The IBD subtypes, Crohn's disease, ulcerative colitis, and IBD-Unspecified, each have characteristic features, but heterogeneity remains even among the subtypes. There has been an explosion of new knowledge on the possible pathogenesis of IBD over the last 2 decades mirroring innovation and refinement in technology, particularly the generation of large scale - "-omic" data. This knowledge has fostered a veritable renaissance of novel diagnostics, prognostics, and therapeutics, with patients with IBD seeing hope bloom in the increasingly large armamentarium of IBD therapies. However, while there are increased numbers of therapies and more pathways being targeted, the number of medications for IBD is still finite and the efficacy has reached a plateau. Precision medicine (PM) is much needed to rationally select and optimize IBD therapies in the new reality of wider but still limited choice with a concurrent, increasingly fine resolution on the significance and utility of clinical, genetic, microbial, and proteomic characteristics that define individual patients. PM is a rapidly changing art, but this review will strive to detail the current state and future directions of PM in pediatric IBD., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Although synthesized nanotherapeutics (NTs) are attractive for the oral treatment of colon diseases, their clinical translations are constrained by the unsatisfactory therapeutic outcomes, potential adverse effects, and high cost of mass production. Here, we report the development of tea leaf-derived natural NTs with desirable particle sizes (140.0 nm) and negative surface charge (-14.6 mV). These natural exosome-like NTs were found to contain large amounts of lipids, some functional proteins, and many bioactive small molecules. Specifically, galactose groups on the surface of NTs could mediate their specific internalization by macrophages via galactose receptor-mediated endocytosis. Moreover, these NTs were able to reduce the production of reactive oxygen species, inhibit the expression of pro-inflammatory cytokines, and increase the amount of anti-inflammatory IL-10 secreted by macrophages. Orally administered NTs could efficiently inhibit the inflammatory bowel responses, restore disrupted colonic barriers and enhance the diversity and overall abundance of gut microbiota, thereby preventing or alleviating inflammatory bowel disease and colitis-associated colon cancer. The present study brings new insights to the facile application of a versatile and robust natural nanoplatform for the prevention and treatment of colon diseases., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In this study, we used DSS to establish an IBD mouse model to study the preventive effect of Lactobacillus plantarum ( L. plantarum ) ZS62 on IBD in the context of oxidative stress and the immune response. We assessed the mitigating effect of this strain on IBD mice by examining the length of and histopathological changes in the colon, determining the serum antioxidant index and the levels of inflammatory cytokines, as well as the mRNA and protein expression levels of relevant genes. The study results showed that L. plantarum ZS62 could inhibit colonic atrophy in IBD mice, reduce the degree of colonic damage, downregulate the serum levels of MDA, MPO, IL-1 β , IL-6, IL-12, TNF- α , and IFN- γ and the relative mRNA and protein expression of IL-1 β , IL-12, TNF- α , COX-2, iNOS, and NF- κ B p65 in mouse colon tissues, and upregulate the serum levels of CAT, T-SOD, and IL-10 and the relative mRNA and protein expression of Cu/Zn SOD, Mn SOD, GSH-Px, CAT, IL-10, and I κ B- α in colon tissues. In summary, L. plantarum ZS62 exhibited a good preventive effect on DSS-induced IBD by regulating oxidative stress and the immune response., Competing Interests: The authors declare no conflict of interest in this article., (Copyright © 2021 Yanni Pan et al.)

Inflammatory bowel disease [IBD] is a complex chronic disorder with no clear aetiology and no known cure. Despite recent advances in overall disease management and improved therapeutics, patients with IBD still experience a substantial burden. Furthermore, as the incidence continues to increase in developing areas of the world, it is expected that the burden of IBD to society will increase and exert tremendous pressure on health care systems worldwide. Therefore, new strategies to prevent the global increase of IBD are urgently required. Data are being progressively acquired on the period preceding disease diagnosis, which support the concept that IBD has a preclinical period that may reveal the triggers of disease and may be amenable to early intervention. Having a better knowledge of this preclinical period will increase the potential not only for improved understanding of disease pathogenesis and improved therapeutics, but also for disease prediction and prevention., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The coronavirus disease (COVID-19) pandemic affects medical care worldwide, including patients with inflammatory bowel disease (IBD). Thus, we aimed to assess its impact on health care provision, fear of infection, adherence to medical treatment, and compliance with preventative instructions in children and adolescents with IBD., Methods: A cross-sectional telephonic survey using a Likert scale-based questionnaire was conducted among all pediatric patients with IBD from a single tertiary medical center., Results: A total of 244 pediatric patients with IBD were included in the study, reporting a high rate of fear of severe COVID-19 infection due to IBD or IBD medications (198, 81.1%). Most of the patients obeyed the Ministry of Health instructions (228, 93.4%), while almost 50% took additional protective measures including avoidance of school and complete lockdown. Concerns regarding the attendance of regular clinics (116, 47.5%) and emergency room in case of IBD exacerbation (178, 73%) were frequently reported. Only 7 patients (2.9%) changed or discontinued their IBD treatment due to COVID-19., Conclusion: We noted several distinct features of the COVID-19 pandemic effect on pediatric patients with IBD including a high rate of fear of severe COVID-19 infection, fear of attending necessary medical facilities, and high rate of avoidance of social activities., Impact: Pediatric patients with IBD have a high rate of fear of severe COVID-19 infection, fear of attending necessary medical facilities, and a high rate of avoidance of social activities. Medication adherence rate in pediatric patients with IBD during the pandemic is similar to the adherence rate among adults with IBD. Almost 50% of pediatric patients with IBD took additional protective measures including avoidance of school and voluntary lockdown during the COVID-19 pandemic., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

The intestinal barrier is vital for preventing inflammatory bowel disease (IBD). This study aimed to investigate the potential mechanism behind the protective effects of B. dentium N8 on the intestinal barrier using the lipopolysaccharide (LPS)-induced Caco-2 cells model. Our probiotic validation results showed that B. dentium N8 had a higher adhesion ability and a more substantial inhibition effect on Escherichia coli ATCC 25922 adhesion to HT-29 cells. Regarding the epithelial integrity, B. dentium N8 significantly increased the trans-epithelial electrical resistance (TEER) value and decreased the paracellular permeability of Caco-2 cells stimulated by lipopolysaccharide (LPS). In addition, B. dentium N8 significantly increased ZO-1, occludin, and claudin-1 mRNA expression. B. dentium N8 downregulated the mRNA expression level of TLR4 and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). Furthermore, B. dentium N8 had a better protective effect on the intestinal barrier than that of E7. Comparative genomics of B. dentium N8 and E7 showed B. dentium N8 had the specific genes encoding for adhesion ability and immune system regulation. The findings provide the theoretical basis for B. dentium N8 possessing a protective effect on the intestinal barrier, which indicate that it could be used as a novel therapy for IBD.

Selenium (Se) is an essential micronutrient that has implications in human diseases, including inflammatory bowel disease (IBD), especially with respect to Se deficiencies. Recently, selenium nanoparticles (SeNPs) have attracted significant attention due to their diversity of biological activities and unique advantages including low toxicity and high biological availability. In this study, an eco-friendly, efficient and low-cost method for synthesis of SeNPs by Kluyveromyces lactis GG799 (K. lactis GG799) was established, and the SeNPs were investigated for their physicochemical properties and anti-inflammatory activities in vivo. K. lactis GG799 was able to successfully transform sodium selenite into bright-red SeNPs with particle sizes of 80 and 150 nm and the nanoparticles accumulated intracellularly. Upon isolation, the SeNPs were found to be mainly capped by proteins and polysaccharides by components analysis. Dietary supplementation with 0.6 mg kg-1 Se (in the form of biogenic SeNPs) effectively attenuated dextran sulphate sodium (DSS)-induced ulcerative colitis (UC) in mice by alleviating oxidative stress and intestinal inflammation. These findings suggested that SeNPs synthesized by K. lactis GG799 may be a promising and safe Se supplement for the prevention and treatment of IBD.

Abstract: This article discusses the "bidirectional" relationship between inflammatory bowel disease (IBD) and physical activity. Intestinal symptoms and extraintestinal manifestations of IBD negatively impact a patient's ability to participate in sports. IBD also impacts athletic performance via its effects on muscle mass, muscle function, bone density, and fatigue. Surveys of IBD patients consistently show that IBD interferes with athletic participation. While IBD negatively affects physical activity, there is growing evidence that physical activity can be beneficial for IBD patients. Prospective studies have revealed that structured physical activities may positively influence inflammatory markers, disease activity, muscle strength, bone density, fatigue, stress, anxiety, and quality of life. This suggests that physical activity may be a simple and safe adjuvant therapy for IBD patients. Future studies assessing the optimal activity regimen are warranted. Finally, a cohort of professional athletes with IBD are described for the first time - football players in the National Football League., (Copyright © 2021 by the American College of Sports Medicine.)

Gut microbiota dysbiosis is a common feature in colorectal cancer (CRC) and inflammatory bowel diseases (IBD). Adoption of the Mediterranean diet (MD) has been proposed as a therapeutic approach for the prevention of multiple diseases, and one of its mechanisms of action is the modulation of the microbiota. We aimed to determine whether MD can be used as a preventive measure against cancer and inflammation-related diseases of the gut, based on its capacity to modulate the local microbiota. A joint meta-analysis of publicly available 16S data derived from subjects following MD or other diets and from patients with CRC, IBD, or other gut-related diseases was conducted. We observed that the microbiota associated with MD was enriched in bacteria that promote an anti-inflammatory environment but low in taxa with pro-inflammatory properties capable of altering intestinal barrier functions. We found an opposite trend in patients with intestinal diseases, including cancer. Some of these differences were maintained even when MD was compared to healthy controls without a defined diet. Our findings highlight the unique effects of MD on the gut microbiota and suggest that integrating MD principles into a person's lifestyle may serve as a preventive method against cancer and other gut-related diseases.

Euphausia superba , commonly known as krill, is a small marine crustacean from the Antarctic Ocean that plays an important role in the marine ecosystem, serving as feed for most fish. It is a known source of highly bioavailable omega-3 polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid). In preclinical studies, krill oil showed metabolic, anti-inflammatory, neuroprotective and chemo preventive effects, while in clinical trials it showed significant metabolic, vascular and ergogenic actions. Solvent extraction is the most conventional method to obtain krill oil. However, different solvents must be used to extract all lipids from krill because of the diversity of the polarities of the lipid compounds in the biomass. This review aims to provide an overview of the chemical composition, bioavailability and bioaccessibility of krill oil, as well as the mechanisms of action, classic and non-conventional extraction techniques, health benefits and current applications of this marine crustacean.

Background: In addition to their potent lipid-lowering action, statins may modulate inflammation. However, data on statin use and the risk of inflammatory bowel diseases [IBD] have been inconsistent., Methods: We searched the Nationwide Swedish Patient Register [inpatient and non-primary outpatient care] to identify adults diagnosed with Crohn's disease [CD, n = 7637] or ulcerative colitis [UC, n = 15 652] from 2006 to 2014. Each case was matched to 10 general population controls [n = 232 890]. Data on dispensed statin prescriptions were extracted from the Prescribed Drug Register. Conditional logistic regression models estimated odds ratios [ORs] for risk of IBD according to statin exposure while controlling for potential confounders, including indications for statin therapy., Results: In multivariable adjusted models, compared with no statin use, any statin use was associated with a lower risk of CD (OR = 0.71; 95% confidence interval [CI], 0.63-0.79), but not UC [OR = 1.03; 95% CI, 0.96-1.11]. The lowest OR for CD was seen for current statin use [OR = 0.67; 95% CI, 0.60-0.75]. For CD, the lowest category of cumulative statin dose [31-325 defined daily dose, DDD] was associated with an OR of 0.73 [95% CI, 0.61-0.88] and the highest category [>1500 DDD] with an OR of 0.66 [95% CI, 0.55-0.80], ptrend = 0.10. For UC, the lowest and highest dose categories yielded ORs of 1.12 [95% CI, 1.00-1.25] and 0.99 [95% CI, 0.88-1.13], respectively, ptrend = 0.13., Conclusions: Statin use was associated with a lower risk of CD, but not of UC. The association with CD risk appeared strongest for current statin use. Our findings suggest that statin use may influence the development of CD., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background: Increasing evidence shows that microRNA-7a-5p (miR-7a-5p) plays an important role in regulating the inflammatory process in inflammatory bowel disease (IBD). How miR-7a-5p contributes to this process is poorly defined. The purpose of this study was to examine whether miR-7a-5p regulates 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced inflammatory responses via the JNK pathway., Methods: Colitis was induced in male mice by intracolonic administration of TNBS; mice were divided into 3 groups: normal control (NC), TNBS, and miR-7a-5p antagomir-treated group. Inflammatory responses were estimated by disease activity index (DAI) and histological scores. The relative expressions of miR-7a-5p and tight junction protein, ZO-1, were detected by RT-qPCR. Western blot assays were used to estimate the level of JNK pathway proteins and ZO-1. After miRNA-antagomir injection, the extent of colonic tissue injury and expression levels of ZO-1 and JNK in intestinal tissue were compared., Results: miR-7a-5p and p-JNK expression were higher in the intestinal tissue of the TNBS group as compared to NC. Inhibition of the expression of miR-7a-5p resulted in significantly decreased expression of p-JNK but increased expression of ZO-1 and promoted the recovery of intestinal mucosa., Conclusion: This work demonstrates a correlation between the JNK pathway and miR-7a-5p in TNBS-induced experimental colitis in mice, which may provide a new research direction for the treatment of IBD.

This register-based national cohort study of 206,900 individuals investigated whether prenatal exposure to small extra doses of vitamin D from fortified margarine prevented inflammatory bowel disease (IBD) later in life; whether the risk of IBD varied according to month or season of birth; and finally, whether there was an interaction between exposure to extra D vitamin and month or season of birth. Fortification of margarine with vitamin D was mandatory in Denmark from the mid-1930s until 1st June 1985, when it was abolished. Two entire birth cohorts, each including two years, were defined: one exposed and one unexposed to the fortification policy for the entire gestation. All individuals were followed for 30 years from the day of birth for an IBD diagnosis in Danish hospital registers. Logistic regression analyses were used to estimate odds ratios (OR) and 95% confidence intervals (CI). Odds for IBD was lower among those exposed to extra D vitamin compared to those unexposed, OR = 0.87 (95% CI: 0.79; 0.95). No association with month or season of birth was found. However, estimates suggested that particularly children born during autumn may have benefitted from the effect of small extra doses of vitamin D. This is, to our knowledge, the first study to explore if prenatal exposure to vitamin D from fortification influenced the risk of IBD. Our results suggest that prenatal exposure to small amounts of extra vitamin D from food fortification may protect against the development of IBD before 30 years of age.

Hericium erinaceus ( H. erinaceus ) is widely studied as a medicinal and edible fungus. Recent studies have shown that H. erinaceus has protective effects for diseases, such as inflammatory bowel disease and cancer, which are related to gut microbiota. To investigate the benefits of H. erinaceus intake on gut microbiota and blood indices in adulthood, we recruited 13 healthy adults to consume H. erinaceus powder as a dietary supplement. Blood changes due to H. erinaceus consumption were determined by routine hematological examination and characterized by serum biochemical markers. Microbiota composition was profiled by 16S ribosomal RNA gene sequencing. Results showed that daily H. erinaceus supplementation increased the alpha diversity within the gut microbiota community, upregulated the relative abundance of some short-chain fatty acid (SCFA) producing bacteria ( Kineothrix alysoides , Gemmiger formicilis , Fusicatenibacter saccharivorans , Eubacterium rectale , Faecalibacterium prausnitzii ), and downregulated some pathobionts ( Streptococcus thermophilus , Bacteroides caccae , Romboutsia timonensis ). Changes within the gut microbiota were correlated with blood chemical indices including alkaline phosphatase (ALP), low-density lipoprotein (LDL), uric acid (UA), and creatinine (CREA). Thus, we found that the gut microbiota alterations may be part of physiological adaptations to a seven-day H. erinaceus supplementation, potentially influencing beneficial health effects.

Triggering receptor expressed on myeloid cell-1 (TREM-1) signaling is expressed on neutrophils and monocytes that is necessary for the successful antimicrobial response and resolution of inflammation in the gut. In this study, we determined the effect of an anti-TREM-1 agonistic antibody (α-TREM-1) on colitis and identify its underlying mechanism of action. Administration of α-TREM-1 alleviated colitis in mice and resolved dysbiosis, which required TLR4/Myd88 signaling. α-TREM-1 increased the production of neutrophil extracellular traps and interleukin-22 by CD177 + neutrophils, which led to pathogen clearance and protection of the intestinal barrier. TREM-1 activation using an α-TREM-1 antibody protects against colitis by rebalancing the microbiota and protecting the epithelium against the immune response as well as modulates the function of neutrophils and macrophages. These results highlight the importance of the TREM-1 pathway in intestinal homeostasis and suggest that α-TREM-1 treatment may be an effective therapeutic strategy for inflammatory bowel disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Seo, Che, Kim, Kim, Ma, Kim, Kim, Kim, Kim and Cheon.)

Regenerating islet-derived protein 1-alpha (REG1A) was abnormally upregulated in a series of gastrointestinal inflammatory disorders. However, the potential biological function and underlying regulatory mechanisms of the increased REG1A in inflammatory bowel disease (IBD) pathogenesis remain to be fully elucidated. In this study, we uncovered that REG1A was substantially increased in the inflamed colorectal tissues of IBD patients. And the aberrantly expressed REG1A in intestinal epithelial cells (IEC) prominently inhibited inflammatory responses, promoted cell proliferation and suppressed epithelial apoptosis. Mechanically, IL-6 and IL-22 markedly activated REG1A transcription through triggering JAK/STAT3 signaling pathway. In addition, overexpression of REG1A in mice by systematic delivery of REG1A lentivirus remarkably alleviated DSS-induced inflammatory injury and maintained the integrity of intestinal mucosal barrier. Taken together, our data demonstrated that the novel proliferative factor REG1A controlled by IL-6/IL-22-JAK-STAT3 signaling may provide a promising therapeutic target for patients with IBD., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Lactose intolerance affects 33% to 75% of the world population and may be associated with various genetic factors. Lactose in the diet can be found in milk and dairy products, which simultaneously constitute the primary sources of calcium. Gut microbiota also influences lactose tolerance. Patients with lactose intolerance often stop consuming milk and dairy products, which may lead to calcium and vitamin deficiency and osteoporosis. Insufficient production of lactase also occurs in patients with diseases of the gastrointestinal tract, such as inflammatory bowel diseases. Moreover, Crohn's disease and ulcerative colitis are risk factors for osteoporosis, and the intake of the proper amount of calcium is an essential element in preventing the decrease of bone mineral density. Diet may prevent the development of osteoporosis, thus, educating patients regarding proper diet should constitute a part of the treatment and prevention process. Patients should consume low-lactose, or lactose-free milk and bacterially fermented dairy products. Additionally, plant milk supplemented by calcium and vitamin D, mineral water with calcium, and certain vegetables also may be good sources of calcium., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Lactobacillus casei , one of the most widely used probiotics, has been reported to alleviate multiple diseases. However, the effects of this species on intestinal diseases are strain-specific. Here, we aimed to screen L. casei strains with inflammatory bowel disease (IBD)-alleviating effects based on in vitro physiological characteristics. Therefore, the physiological characteristics of 29 L. casei strains were determined, including gastrointestinal transit tolerance, oligosaccharide fermentation, HT-29 cell adhesion, generation time, exopolysaccharide production, acetic acid production, and conjugated linoleic acid synthesis. The effects of five candidate strains on mice with induced colitis were also evaluated. The results showed that among all tested L. casei strains, only Lactobacillus casei M2S01 effectively relieved colitis. This strain recovered body weight, restored disease activity index score, and promoted anti-inflammatory cytokine expression. Gut microbiota sequencing showed that L. casei M2S01 restored a healthy gut microbiome composition. The western blotting showed that the alleviating effects of L. casei M2S01 on IBD were related to the inhibition of the NF-κB pathway. A good gastrointestinal tolerance ability may be one of the prerequisites for the IBDalleviating effects of L. casei . Our results verified the efficacy of L. casei in alleviating IBD and lay the foundation for the rapid screening of L. casei strain with IBD-alleviating effects.

Aim: Our aim was to compare the risk of developing inflammatory bowel disease [IBD] between ever users and never users of metformin., Methods: Patients with newly diagnosed type 2 diabetes mellitus from 1999 to 2005 were enrolled from Taiwan's National Health Insurance. A total of 340 211 ever users and 24 478 never users who were free from IBD on January 1, 2006 were followed up until December 31, 2011. Hazard ratios were estimated by Cox regression incorporating the inverse probability of treatment weighting using a propensity score., Results: New-onset IBD was diagnosed in 6466 ever users and 750 never users. The respective incidence rates were 412.0 and 741.3 per 100 000 person-years and the hazard ratio for ever vs never users was 0.55 [95% confidence interval: 0.51-0.60]. A dose-response pattern was observed while comparing the tertiles of cumulative duration of metformin therapy to never users. The respective hazard ratios for the first [<26.0 months], second [26.0-58.3 months] and third [>58.3 months] tertiles were 1.00 [0.93-1.09], 0.57 [0.52-0.62] and 0.24 [0.22-0.26]. While patients treated with oral antidiabetic drugs [OADs] without metformin were treated as a reference group, the hazard ratios for patients treated with OADs with metformin, with insulin without metformin [with/without other OADs] and with insulin and metformin [with/without other OADs] were 0.52 [0.42-0.66], 0.95 [0.76-1.20] and 0.50 [0.40-0.62], respectively., Conclusion: A reduced risk of IBD is consistently observed in patients with type 2 diabetes mellitus who have been treated with metformin., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Damage to the small intestine caused by non-steroidal anti-inflammatory drugs (NSAIDs) occurs more frequently than in the upper gastrointestinal tract, is more difficult to diagnose and no effective treatments exist. Hence, we investigated whether probiotics can control the onset of this severe condition in a murine model of intestinal inflammation induced by the NSAID, indomethacin. Probiotic supplementation to mice reduce the body weight loss, anemia, shortening of the small intestine, cell infiltration into the intestinal tissue and the loss of Paneth and Goblet cells associated with intestinal inflammation. Furthermore, a high antimicrobial activity in the intestinal fluids of mice fed with probiotics compared to animals on a conventional diet was elicited against several pathogens. Interestingly, probiotics dampened the oxidative stress and several local and systemic markers of an inflammatory process, as well as increased the secretion of IL-10 by regulatory T cells. Even more importantly, probiotics induced important changes in the large intestine microbiota characterized by an increase in anaerobes and lactobacilli, and a significant decrease in total enterobacteria. We conclude that oral probiotic supplementation in NSAID-induced inflammation increases intestinal antimicrobial activity and reinforces the intestinal epithelial barrier in order to avoid pathogens and commensal invasion and maintain intestinal homeostasis.

Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract (GIT), including Crohn's disease (CD) and ulcerative colitis (UC), which differ in the location and lesion extensions. Both diseases are associated with microbiota dysbiosis, with a reduced population of butyrate-producing species, abnormal inflammatory response, and micronutrient deficiency (e.g., vitamin D hypovitaminosis). Vitamin D (VitD) is involved in immune cell differentiation, gut microbiota modulation, gene transcription, and barrier integrity. Vitamin D receptor (VDR) regulates the biological actions of the active VitD (1α,25-dihydroxyvitamin D3), and is involved in the genetic, environmental, immune, and microbial aspects of IBD. VitD deficiency is correlated with disease activity and its administration targeting a concentration of 30 ng/mL may have the potential to reduce disease activity. Moreover, VDR regulates functions of T cells and Paneth cells and modulates release of antimicrobial peptides in gut microbiota-host interactions. Meanwhile, beneficial microbial metabolites, e.g., butyrate, upregulate the VDR signaling. In this review, we summarize the clinical progress and mechanism studies on VitD/VDR related to gut microbiota modulation in IBD. We also discuss epigenetics in IBD and the probiotic regulation of VDR. Furthermore, we discuss the existing challenges and future directions. There is a lack of well-designed clinical trials exploring the appropriate dose and the influence of gender, age, ethnicity, genetics, microbiome, and metabolic disorders in IBD subtypes. To move forward, we need well-designed therapeutic studies to examine whether enhanced vitamin D will restore functions of VDR and microbiome in inhibiting chronic inflammation.

There is growing evidence that inflammatory bowel disease has a preclinical phase that precedes disease symptoms, during which immune system activation has already occurred and inflammatory pathways have been primed, setting the stage for disease to expand and leading up to clinical diagnosis. Gaining insight to this pre-diagnosis period could improve our knowledge about disease pathogenesis and potentially result in the detection of biomarkers that could predict disease development. The ultimate goal of such research is to identify a population at risk for developing IBD, so preventive strategies could be implemented and disease prevention be achieved., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Inflammatory bowel disease (IBD) is one of the major complications of the gastrointestinal tract, characterized by chronic inflammation, which disturbs the quality of life of the affected individuals. Genetic predisposition, immune, inflammatory, and enzyme-mediated signaling cascades are the primary mechanisms involved in the pathogenesis of the disease. Currently, the treatment strategy involves the maintenance of remission and induction of inflammation by anti-inflammatory agents and immune suppressants. Polyphenol-containing diets, including fruits and vegetables of regular use, possess anti-inflammatory, and antioxidant potential through the inhibition of major contributing pathways to IBD. This review discusses the role of these dietary polyphenols in downregulating the major signaling cascades in IBD. Our review encourages the development of nutritional strategies to improve the efficiency of current therapies for IBD and reduce the risks of side effects associated with conventional therapy. PRACTICAL APPLICATIONS: At present, almost every third person in society is under stress and having chronic disorders like diabetes, arthritis, allergy, cardiovascular disease, IBD, etc. This insists on the direct/indirect role of changes in the lifestyle for such deterioration in society. This review would emphasize the medicinal value of polyphenols present in fruits and vegetables for chronic inflammatory disorders. This concept portrays the food components which have the potential to promote health, improve general well-being, and reduce the risk of IBD. We propose to add fruits with bioactive polyphenols in the regular diet to help in preventing the immune-mediated intestinal chronic inflammatory syndrome and reduce the risks of colorectal cancer development., (© 2020 Wiley Periodicals LLC.)

Patients with inflammatory bowel disease (IBD) have higher rates of psychiatric pathology, including anxiety and depression. The dextran sulfate sodium (DSS)-treated mouse is a well-characterized animal model of colitis that exhibits IBD-like and depressive-like changes. A recent study found that phosphorylated (p-) adenosine monophosphate-activated protein kinase (AMPK) was associated with anti-inflammatory and antidepressant effects. Our previous research in an animal model of major depression suggests that liver hydrolysate (LH) has an antidepressant effect and combats physical fatigue by enhancement via the hippocampal or peripheral p-AMPK pathway. In this study, we examined whether or not LH has antidepressant and anti-inflammatory effects in mice with DSS-induced changes. We evaluated colon inflammation in DSS-treated mice and used the tail suspension and forced swimming tests to confirm whether or not LH prevents IBD-like symptoms and depressive-like behavior. Hippocampal expression of AMPK, brain-derived neurotrophic factor (BDNF), doublecortin, and neuronal nuclear antigen proteins was assessed by Western blotting. Hippocampal neurogenesis and morphometric changes in the microglia and astrocytes were examined by immunohistochemistry. DSS-treated mice showed IBD-like pathology and depressive-like behavior, a reduction in the hippocampal neuronal nuclear antigen level and neurogenesis, and increased hippocampal activation of microglia and astrocytes. These changes were reversed by LH. DSS-treated mice showed enhanced hippocampal expression of p-AMPK and BDNF after administration of LH. LH prevented depressive-like behavior by enhancing hippocampal neurogenesis through the AMPK/BDNF pathway and anti-neuroinflammation in the hippocampus. LH may be a therapeutic option for patients with IBD and depression., Competing Interests: Declaration of Competing Interest Kotaro Yamada is an employee of Zeria Pharmaceutical Co., Ltd. (Tokyo, Japan)., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Disturbed activation of autophagy is implicated in the pathogenesis of inflammatory bowel disease. Accordingly, several autophagy-related genes have been identified as Crohn's disease susceptibility genes. We screened the autophagy activators from a library including 3,922 natural extracts using a high-throughput assay system. The extracts identified as autophagy activators were administered to mice with 2% dextran sodium sulfate (DSS). Among the autophagy inducers, Sanguisorba officinalis L. (SO) suppressed DSS-induced colitis. To identify the mechanism by which SO ameliorates colitis, epithelial cell and innate myeloid cells-specific Atg7-deficient mice (Villin-cre; Atg7 f/f and LysM-cre; Atg7 f/f mice, respectively) were analyzed. SO-mediated inhibition of colitis was observed in Villin-cre; Atg7 f/f mice. However, SO and a mixture of its components including catechin acid, ellagic acid, gallic acid, and ziyuglycoside II (Mix 4 ) did not suppressed colitis in LysM-cre; Atg7 f/f mice. In large intestinal macrophages (Mφ) of Atg7 f/f mice, SO and Mix 4 upregulated the expression of marker genes of anti-inflammatory Mφ including Arg1, Cd206, and Relma. However, these alterations were not induced in LysM-cre; Atg7 f/f mice. These findings indicate that SO and its active components ameliorate DSS-induced colitis by providing intestinal Mφ with anti-inflammatory profiles via promotion of Atg7-dependent autophagy.