Ferric carboxymaltose for anemia in Crohn's disease patients at a tertiary center: A retrospective observational cohort study.

BACKGROUND: Although the gastrointestinal tract is the most affected by Crohn's disease (CD), the condition triggers other consequent manifestations, and iron deficiency anemia (IDA) is one of the most common. Intravenous (IV) iron replacement is currently available through several drugs, such as ferric hydroxide sucrose and ferric carboxymaltose (FCM). However, the clinical management of these conditions can be challenging. AIM: To elucidate the drug's effectiveness, the present study analyzed, through medical records, the clinical and epidemiological data of a cohort of patients with active CD who received IV FCM for the IDA treatment. METHODS: This retrospective observational study included 25 patients with active CD, severe anemia, and refractory to previous conventional treatments. Patients were evaluated two times: During the last treatment with ferric hydroxide sucrose and treatment with FCM. RESULTS: After treatment with FCM, parameters of IDA assessment significantly improved, serum hemoglobin (Hb) levels increased in 93% of patients (P < 0.0001), and in 44%, there was an increase of ≥ 2 g/dL in a single application. In addition, 86% of the patients showed an increase in serum iron (P < 0.0001) and ferritin (P = 0.0008) and 50% in transferrin saturation (P = 0.01). The serum iron levels at baseline showed a negative association with the ileal and colonic CD and use of biologics and a positive association with patients who developed CD later in life after the age of 40 (A3) and with a stenosing (B2) and fistulizing (B3) phenotype. The values of Hb and hematocrit after ferric hydroxide sucrose treatment remained similar to those found before treatment. CONCLUSION: This study demonstrated that FCM is an important therapeutic strategy for treating IDA in CD patients, achieving satisfactory results in refractory cases.

Pouchitis: insight into the pathogenesis and clinical aspects.

Ulcerative colitis (UC) is a chronic intestinal inflammatory disease and familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease. Both diseases, despite being different, may require the same surgical procedure: proctocolectomy with ileal pouch-anal anastomosis (IPAA). The main complication after this procedure is pouch inflammation (pouchitis). This inflammatory complication can affect up to 60 percent of patients who receive IPAA for UC, and a very small percentage of the FAP patients. The purpose of this review was to determine the current molecular mechanisms in its pathogenesis and detail the risk factors involved in pouchitis, its diagnosis, and treatment.

Mucinous adenocarcinoma in perianal fistula in Crohn's disease: Case report and literature review.

INTRODUCTION AND IMPORTANCE: Crohn's disease (CD) is a chronic bowel disease that, due to exacerbated inflammation, can lead to complications such as the development of perianal fistulas. The development of mucinous adenocarcinoma in perianal fistulas in patients with CD is rare and, consequently, few reports exist in the literature. CASE PRESENTATION: We report the case of a 71-year-old man diagnosed 22 years ago with CD with perineal involvement, who came with complaints of intense perianal pain, a gluteal mass, and local bleeding. Tomography of his abdomen showed an expansive, heterogeneous, and solid perianal mass on the right, with interspersed necrotic/liquefied areas and possible mucinous content. The patient was referred to the surgery department for an incisional biopsy, which confirmed mucinous adenocarcinoma. The patient underwent extra levator abdominoperineal rectal resection (APR) with partial prostatectomy. CLINICAL DISCUSSION: Perineal mucinous adenocarcinoma arising in a fistula associated with CD is very rare. Since the symptoms overlap, early diagnosis of malignancy is difficult. Histological analysis is the gold standard for its diagnosis. Surgical resection through APR is well-established and, despite being a complex procedure with potential complications, tends to have good results. However, the locoregional and inguinal lymph node involvement was related to a worse progression in this case. CONCLUSION: The diagnostic hypothesis of mucinous adenocarcinoma should be suspected in CD patients who present long-term perineal involvement with fistulas. Biopsies and imaging exams should be performed to aid the diagnosis of the condition and thus contribute to the surgical plan.

Endoplasmic Reticulum Stress in Colonic Mucosa of Ulcerative Colitis Patients Is Mediated by PERK and IRE1 Pathway Activation.

Ulcerative colitis (UC) is characterized by a chronic overproduction of proinflammatory cytokines. During an acute phase, the endoplasmic reticulum (ER) is overloaded and the protein folding process is impaired, a condition named ER stress. This state induces a response (unfolded protein response (UPR)), initiated by the activation of IRE1/Xbp-1, PERK/eIF2α, and ATF6 pathways, which has previously been linked to intestinal inflammation in experimental models. ER stress and UPR activation trigger the activation of proinflammatory, autophagy, and apoptosis genes, in addition to promoting protein degradation. Therefore, the goal of this study was to evaluate the activation of ER stress and UPR in colonic mucosa of UC patients. Patient and Methods. Transcriptional analysis of ER stress- and UPR-related genes was performed by qPCR from intestinal mucosa of patients with UC. We also performed in situ hybridization (ISH) and immunohistochemistry (IHQ) of PERK/eIF2α and IRE1/Xbp-1 pathways and UPR-related chaperones. Results. We first evaluated inflammatory genes via qPCR, and we observed that all analyzed proinflammatory transcripts were upregulated in UC patients. ISH and IHQ images showed that ER stress is activated via PERK/eIF2α and IRE1/Xbp-1 pathways not only in intestinal epithelial cells but also in cells of the lamina propria of UC colonic mucosa. Transcriptional analysis confirmed that EIF2AK3 was upregulated in UC patients. UPR-related genes, such as ATF3, STC2, and DDIT3, along with the chaperones and cochaperones DNAJC3, CALR, HSP90B1, and HSPA5, were also upregulated in UC patients. In addition, we observed that proapoptotic and autophagy genes (Bax and ATG6L1, respectively) were also upregulated. Conclusion. Our results suggest that ER stress and UPR are indeed activated in UC patients and this may contribute to the chronic inflammatory process seen in UC. The increased apoptosis and autophagy markers further support the activation of these findings once they are activated to counterbalance tissue damage. These findings provide new insights into the molecular mechanisms that maintain UC activity and open new possibilities to attenuate intestinal inflammation.

New translational and experimental insights into the role of pro-resolving lipid mediators in inflammatory bowel disease.

The resolution of inflammation is an active process, guided by specialized pro-resolution lipid mediators (SPMs). These mediators originate from polyunsaturated fatty acids, such as omega-3. Sufficient evidence suggests that the beneficial effects attributed to omega-3 are, at least in part, the result of the immunomodulatory action of the SPMs, which act systemically by overcoming inflammation and repairing tissue damage, without suppressing the immune response. Recent studies suggest that an imbalance in the synthesis and/or activity of these compounds may be associated with the pathogenesis of several inflammatory conditions, such as inflammatory bowel disease (IBD). Thus, this review highlights the advances made in recent years with regard to the endo-genous synthesis and the biological role of lipoxins, resolvins, protectins, and maresins, as well as their precursors, in the regulation of inflammation; and provides an update on the participation of these mediators in the development and evolution of IBD and the therapeutic approaches that these immunomodulating substances are involved in this context.

Interesterified palm oil increases intestinal permeability, promotes bacterial translocation, alters inflammatory parameters and tight-junction protein genic expression in Swiss mice.

High-fat diets seem to have a negative influence on the development of obesity and the processes associated with low-grade chronic systemic inflammation. In recent years, partial hydrogenated oil, rich in trans isomers, has been associated with deleterious health effects. It has been replaced by interesterified fat (IF). However, there is no evidence whether IF ingestion can exert adverse effects on the intestinal mucosa. Thus, this study aimed to evaluate the effect of IF on the intestinal mucosa of male Swiss mice fed a normal or high-fat diet, focusing on its effects on intestinal permeability and bacterial translocation and its possible damage to the intestinal epithelium. The animals were divided into 4 groups: Control (C) and Interesterified Control (IC) groups (10 En% lipids from unmodified fat or interesterified fat, respectively) and High Fat (HF) and Interesterified High Fat (IHF) groups (45 En% lipids from unmodified fat or interesterified fat, respectively). Compare to C, the IC, HF, and IHF groups presented flattened epithelium, a shorter villi length and a lower percentage of goblet cells, less mucin 2, an increased oxidative stress and more inflammatory cells, higher IL-1ß, IL-17, and IL-23 levels. These groups also presented increased intestinal permeability and gene expression of the protein claudin 2, while JAM-A and claudin 1 gene expression was reduced. IC and IHF increased IL-6 levels while reducing occludin expression. In addition, the IC group also presented a mucosa with lesions of low intensity in the ileum, an increased mucin 5ac, TNF-α levels, and reduced occludin expression in the distal jejunum. Moreover, there was a significant increase in bacterial translocation in the IC group to blood, liver, and lungs, while HF and IHF groups presented bacterial translocation which was restricted to the mesenteric lymph nodes. In summary, our results supported the hypothesis that IF added to a normolipidic diet can be considered harmful or even worse when compared to a HF.

EPIDEMIOLOGICAL PROFILE AND CLINICAL CHARACTERISTICS OF INFLAMMATORY BOWEL DISEASES IN A BRAZILIAN REFERRAL CENTER.

BACKGROUND: The increase in the incidence and prevalence rates of inflammatory bowel disease (IBD) is evident in many newly industrialized countries in Asia, Africa, Eastern Europe, and the American continent. In Brazil, records are still scarce, and further studies on this topic are needed. OBJECTIVE: To evaluate the epidemiological profile and clinical characteristics of patients with IBD who were followed up at a reference service in the state of São Paulo. METHODS: We retrospectively analyzed the medical records of patients with IBD who were followed up in a Brazilian Referral Center. RESULTS: A total of 625 patients was evaluated, 416 with Crohn's disease (CD), 190 with ulcerative colitis (UC), and 19 with indeterminate colitis. The average age of the patients was 31.6 years, with a homogeneous distribution between males and females patients. In patients with CD, the most predominant Montreal classification was A2, L3, and B1, with 44.8% of patients presenting with perianal disease; in UC, it was E2, and S0. The main extraintestinal manifestation was rheumatologic, followed by cutaneous and ophthalmic lesions. The majority of patients (85.4%) used some type of medication, the most frequent being aminosalicylates in patients with UC and biological therapy in patients with CD. Regarding surgeries, in CD, a significant percentage of patients underwent some type of surgical procedure, unlike the UC patients, including fistulotomies and placement of seton, derivative ostomies, enterectomy, ileocecectomy/right colectomy, total or partial colectomy, and strictureplasty. Only 195 (31.2%) patients lived in the city of Campinas, while 443 (70.9%) were from the 7th Regional Health Department (RHD), which corresponds to the macro-region of Campinas. CONCLUSION: In this study, most patients came from the 7th RHD of Campinas; the patients were young, with no predominance of either sex; there was a higher frequency of patients with CD (66.6%). Most of them (85.4%) were undergoing pharmacological treatment, and a significant percentage of CD patients had undergone surgery.

Chemoprevention with a tea from hawthorn (Crataegus oxyacantha) leaves and flowers attenuates colitis in rats by reducing inflammation and oxidative stress.

The purpose of the study was to determine the effects of a tea from the leaves and flowers of Crataegus oxyacantha in rats with colitis. Colitis was induced by administration of 2,4,6-trinitrobenzene sulfonic acid. Hawthorn tea (HT) (100 mg/kg) was given via gavage for 21 days and the mesalamine drug (100 mg/kg) was administrated during the period of disease onset. HT was rich in total phenolic compounds (16.5%), flavonoids (1.8%), and proanthocyanidins (1.5%); vitexin-2-O-rhamnoside was the main compound detected. Mesalamine and the HT diminished the length of the lesions formed in the colon, in addition to reducing the levels of myeloperoxidase and interleukin-1ß. Mesalamine was able to significantly reverse the body weight loss, while HT improved the activity of glutathione reductase and catalase. Histological scoring was not changed by the interventions, but it was highly correlated with the necrotic area. HT given at 100 mg/kg can be effective against colitis.

Perfil epidemiológico e características clínicas das doenças inflamatórias intestinais em um centro de referência Brasileiro / Epidemiological profile and clinical characteristics of inflammatory bowel diseases in a brazilian referral center

ABSTRACT BACKGROUND: The increase in the incidence and prevalence rates of inflammatory bowel disease (IBD) is evident in many newly industrialized countries in Asia, Africa, Eastern Europe, and the American continent. In Brazil, records are still scarce, and further studies on this topic are needed. OBJECTIVE: To evaluate the epidemiological profile and clinical characteristics of patients with IBD who were followed up at a reference service in the state of São Paulo. METHODS: We retrospectively analyzed the medical records of patients with IBD who were followed up in a Brazilian Referral Center. RESULTS: A total of 625 patients was evaluated, 416 with Crohn's disease (CD), 190 with ulcerative colitis (UC), and 19 with indeterminate colitis. The average age of the patients was 31.6 years, with a homogeneous distribution between males and females patients. In patients with CD, the most predominant Montreal classification was A2, L3, and B1, with 44.8% of patients presenting with perianal disease; in UC, it was E2, and S0. The main extraintestinal manifestation was rheumatologic, followed by cutaneous and ophthalmic lesions. The majority of patients (85.4%) used some type of medication, the most frequent being aminosalicylates in patients with UC and biological therapy in patients with CD. Regarding surgeries, in CD, a significant percentage of patients underwent some type of surgical procedure, unlike the UC patients, including fistulotomies and placement of seton, derivative ostomies, enterectomy, ileocecectomy/right colectomy, total or partial colectomy, and strictureplasty. Only 195 (31.2%) patients lived in the city of Campinas, while 443 (70.9%) were from the 7th Regional Health Department (RHD), which corresponds to the macro-region of Campinas. CONCLUSION: In this study, most patients came from the 7th RHD of Campinas; the patients were young, with no predominance of either sex; there was a higher frequency of patients with CD (66.6%). Most of them (85.4%) were undergoing pharmacological treatment, and a significant percentage of CD patients had undergone surgery.

RESUMO CONTEXTO: O aumento na incidência e prevalência das doenças inflamatórias intestinais (DIIs) é evidente em muitos países recém-industrializados da Ásia, África, Europa Oriental e do continente Americano. No Brasil, os registros ainda são bastante escassos, sendo necessários mais estudos sobre este tema. OBJETIVO: Avaliar o perfil epidemiológico e as características clínicas dos doentes com DIIs, acompanhados em um serviço de referência no Estado de São Paulo. MÉTODOS: Análise retrospectiva, descritiva, dos prontuários médicos dos pacientes com DIIs acompanhados em um centro de referência no Brasil. RESULTADOS: Foram avaliados 625 doentes, sendo 416 com doença de Crohn (DC), 190 com retocolite ulcerativa (RCU) e 19 com colite indeterminada. A média de idade foi de 31,6 anos, sendo a distribuição homogênea entre os sexos. Na DC predominou a classificação de Montreal A2 L3 e B1, com 44,8% dos doentes apresentando doença perianal; na RCU, E2 e S0. A principal manifestação extraintestinal presente foi reumatológica, vindo a seguir as lesões cutâneas e as oftalmológicas. A maioria dos doentes (85,4%) fazia uso de alguma medicação, sendo as mais frequentes, aminossalicilatos na RCU e terapia biológica na DC. Em relação às cirurgias, na DC um significativo percentual de pacientes foi submetido a algum tipo de procedimento cirúrgico, ao contrário da RCU, incluindo fistulotomias e colocação de sedenhos, estomas de derivação, enterectomia, ileotiflectomia/colectomia direita, colectomia total ou parcial e plastias intestinais. Apenas 195 (31,2%) doentes eram da cidade de Campinas, mas 443 (70,9%) eram provenientes do 7º Departamento Regional de Saúde (DRS), que corresponde a Grande Campinas. CONCLUSÃO: No estudo, houve um predomínio de pacientes do DRS de Campinas; os doentes eram jovens, sem predominância de sexo; a frequência maior foi de doentes com DC (66,6%). A maioria (85,4%) estava em tratamento farmacológico, e um percentual significativo de doentes com DC, havia sido submetido à cirurgia.

The role of chemokines and adipokines as biomarkers of Crohn's disease activity: a systematic review of the literature.

INTRODUCTION: Crohn's disease (CD) is an inflammatory bowel disease (IBD) that affects the gastrointestinal tract and can have a major impact on the patient's quality of life and social/professional activities. Asymptomatic patients, or those with mild symptoms, experience the active disease with subclinical manifestation. Systematic review (SR) was performed to look for evidence for the role of chemokines and adipokines as markers for CD activity. METHODS: This SR was conducted by searching published studies in international and regional databases up till July, 2020. CD patients were adults with the disease in activity or remission. All adipokines and chemokines were considered for the analysis and the Rayyan QCRI system was used. RESULTS: In total, 20 studies were included. Six addressed chemokines and eight adipokines as potential biomarkers of CD activity. CXCL8 was the most studied chemokine (8 studies) and the results were controversial, with 62.5% showing a significant association with CD activity. CXCL10 was investigated by 4 studies and 50% identified it as a potential biomarker. CCL2, CCL11, CCL26 and CXCL1 were examined by 2 articles each. CXCL8 (P=0.002/P=0.001) and CXCL1 (P<0.001) presented the lowest? P value, which qualifies them as potential markers of disease activity. All the adipokines were tested in peripheral blood but 44.4% were also tested in intestinal mucosa, while the percentage in the chemokines' studies was 76.9% in peripheral blood, 46.1% in intestinal mucosa and 7.6% in urine sample respectively. CONCLUSION: The development of disease activity biomarkers for CD is becoming relevant for clinical practice. Chemokines and adipokines have the potential to signalize CD activity, but validation in larger cohorts of patients, preferable multicenter studies are still needed.

Intestinal Microbiota in the SARS-CoV-2 Infection: What Is Known?

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, emerged last year in China and quickly spread to millions of people around the world. This virus infects cells in different tissues and causes pulmonary (e.g., pneumonia and acute respiratory distress syndrome), neurological, cardiovascular, and intestinal manifestations, which can be the result of a direct viral effect or secondary to endothelial, thrombotic, or immunological alterations. In this chapter, we discuss recent studies which highlighted the relevance of the intestinal microbiota for other infectious respiratory diseases. We present the "altered microbiota" (dysbiotic) as a point of connection between conditions that are risk factors for the development of severe forms of COVID-19. In addition, we describe the findings of recent studies reporting alterations of microbiota composition in COVID-19 patients and speculate on how this may impact in development of the disease.

Role of diet and nutrition in inflammatory bowel disease.

Inflammatory bowel diseases (IBDs) are closely linked to nutrition. The latest research indicates that diet and nutrition are significantly involved in the etiopathogenesis of the disease, although their specific role throughout its clinical course still remains unclear. This study reviewed how diet and nutrition are associated with IBD development and management. Even though specific diets have been shown to bring about positive outcomes, there is currently no scientific consensus regarding an appropriate diet that would benefit all IBD patients. We suggest that individualized dietary recommendations are of the greatest importance and that diets should be planned to provide individual IBD patients with specific nutrient requirements while keeping all the clinical aspects of the patients in mind. Further research is clearly necessary to investigate nutritional factors involved in IBD development and, especially, to evaluate the applications of the diets during the course of the disease.

Microbiota-derived short-chain fatty acids do not interfere with SARS-CoV-2 infection of human colonic samples.

Microbiota-derived molecules called short-chain fatty acids (SCFAs) play a key role in the maintenance of the intestinal barrier and regulation of immune response during infectious conditions. Recent reports indicate that SARS-CoV-2 infection changes microbiota and SCFAs production. However, the relevance of this effect is unknown. In this study, we used human intestinal biopsies and intestinal epithelial cells to investigate the impact of SCFAs in the infection by SARS-CoV-2. SCFAs did not change the entry or replication of SARS-CoV-2 in intestinal cells. These metabolites had no effect on intestinal cells' permeability and presented only minor effects on the production of anti-viral and inflammatory mediators. Together our findings indicate that the changes in microbiota composition of patients with COVID-19 and, particularly, of SCFAs do not interfere with the SARS-CoV-2 infection in the intestine.

Anti-TNF therapy and immunogenicity in inflammatory bowel diseases: a translational approach.

Inflammatory bowel diseases are chronic illnesses that involve intestinal inflammation and are usually diagnosed as Crohn's disease or ulcerative colitis. As these diseases do not have a cure, the goal of treatment is to induce and maintain remission. Monoclonal antibodies have been recognized as the most advanced therapy to avoid complications and reduce the need for surgical approaches. However, although their effectiveness has been proven by several studies, they can trigger the immune system, induce the occurrence of immunogenicity, which may lead to the loss of response and treatment failure. The purpose of this review is to determine what are the main mechanisms involved in IBD; to assess the recommended treatments; to explore the mechanisms of immunogenicity. We also try to explain the detection and describe the existing advances that make possible the clinical application of these approaches.

Assessment of disease activity in inflammatory bowel diseases: Non-invasive biomarkers and endoscopic scores.

Inflammatory bowel diseases (IBD) comprise two major forms: Crohn's disease and ulcerative colitis. The diagnosis of IBD is based on clinical symptoms combined with results found in endoscopic and radiological examinations. In addition, the discovery of biomarkers has significantly improved the diagnosis and management of IBD. Several potential genetic, serological, fecal, microbial, histological and immunological biomarkers have been proposed for IBD, and they have been evaluated for clinical routine and clinical trials. Ileocolonoscopy, especially with biopsy collection, has been considered the standard method to diagnose IBD and to assess clinical activity of the disease, but it is limited to the colon and terminal ileum and is considered invasive. For this reason, non-invasive biomarkers are necessary for this type of chronic inflammatory disease, which affects mostly young individuals, as they are expected to have a long follow-up.

Histological grading evaluation of non-alcoholic fatty liver disease after bariatric surgery: a retrospective and longitudinal observational cohort study.

Non-alcoholic fatty liver disease (NAFLD) is a chronic disease with several degrees of histological features which may progress to cirrhosis. Obesity is an important risk factor and although NAFLD has no specific pharmacological treatment, bariatric surgery has been associated with NAFLD regression in severely obese patients. However, few longitudinal histological studies support this finding. Therefore, firstly, a retrospective study was performed including clinical and histological data of 895 obese patients who underwent bariatric surgery. In addition, histological analyses of 30 patient's liver biopsies were evaluated at two timepoints (T1 and T2). The retrospective analysis of the total number of patients revealed that the average body mass index (BMI) was 35.91 ± 2.81 kg/m2. The liver biopsies during bariatric surgery showed that 53.52% did not present NAFLD, 30.16% had NASH, 15.98% isolated steatosis and 0.34% liver cirrhosis. The median BMI of the longitudinal cohort decreased from 37.9 ± 2.21 kg/m2 at the time of bariatric surgery (T1) to 25.69 ± 3.79 kg/m2 after 21 ± 22 months after the procedure (T2). The prevalence of NAFLD in T1 was 50%, and 16.67% in T2. The histological area of collagen fiber was lower in T2 compared to T1 (p = 0.0152) in the majority of patients, which was also illustrated by immunohistochemistry for Kupffer cell and myofibroblast formation markers. These findings confirmed the NAFLD regression after bariatric surgery and, for the first time, showed the amelioration of these features using more accurate histopathological techniques.

Dietary Patterns Associated to Clinical Aspects in Crohn's Disease Patients.

Diet is an important factor in both the pathogenesis and in the clinical course of Crohn's disease (CD). However, data on dietary patterns of CD patients are rather limited in the literature. This cross-sectional study included 60 patients with CD, aged 18-60 years. Dietary intake was assessed using a validated food frequency questionnaire to measure food consumption patterns by principal component analysis (PCA). Multiple regression analysis was performed to investigate the association between dietary patterns and clinical and demographic variables. Three dietary patterns were identified: "Traditional + FODMAP" was associated with symptoms, gender, previous surgeries, and duration of the disease. "Fitness style" was positively associated with physical activity and negatively associated with body mass index and smoking. "Snacks and processed foods" was positively associated with duration of the disease and negatively associated with age. According to the weekly food consumption analysis, patients with active disease consumed less coffee and tea. We found significant associations between the three dietary patterns and the variables, but not with the stage of the disease. Prospective studies are necessary to determine the effects of food consumption patterns on the clinical course of CD.

Whole transcriptional analysis identifies markers of B, T and plasma cell signaling pathways in the mesenteric adipose tissue associated with Crohn's disease.

BACKGROUND: Crohn's disease (CD) is a multifactorial disease characterized by chronic intestinal inflammation. The increased visceral adiposity near the affected intestinal area, of which mesenteric adipose tissue (MAT) is the main component, is a feature of CD. Both protective and pathological roles have been attributed to this disease-associated tissue in CD. To understand the contribution of MAT to CD pathophysiology, a molecular and cellular signature of disease-associated MAT in CD patients was provided. METHODS: We performed an observational study with whole transcriptional analysis by RNA sequencing (RNA-seq) of MAT and ileal mucosa from CD patients with active disease and controls. qPCR and immunohistology were performed for validation analysis. RESULTS: RNA-seq identified 17 significantly regulated genes (|FC| > 1.5; FDR < 0.05) in CD-MAT compared to non-IBD controls, with a marked upregulation of plasma cell genes (i.e., IGLL5, MZB1, CD79A, POU2AF1, FCRL5, JCHAIN, DERL3, SDC1, PIM2). A less strict statistical cutoff value (|FC| > 1.5, nominal p ≤ 0.05) yielded a larger list of 651 genes in CD-MAT compared to controls. CD ileum showed the significant regulation compared to control ileum of 849 genes (|FC| > 1.5; FDR < 0.05) or 2654 genes (|FC| > 1.5, nominal p ≤ 0.05). Ingenuity Pathway Analysis revealed the significant regulation of pathways related to T- and B cell functionality in the MAT of CD patients. Despite the differences between the MAT and ileal signatures of CD patients, we identified a subset of 204 genes significantly modulated in both tissues compared to controls. This common signature included genes related to the plasma cell signature. Genes such as S100A8, S100A9 (calprotectin) and IL1B, which are associated with acute inflammatory response, were exclusively regulated in the ileal mucosa of CD disease. In contrast, some genes encoding for lymphocyte receptors such as MS4A1, CD3D and CD79A were exclusively regulated in CD-MAT, exhibiting a different pattern of immune cell activation compared to the ileal mucosa in CD patients. qPCR and immunohistology confirmed the presence of large infiltrates of CD3+ CD20+ lymphocytes and CD138+ plasma cells in CD-MAT. CONCLUSION: Our data strongly supports the role of CD-associated MAT as a site for T-, B- and plasma cell activation, and suggests that it could also act as a reservoir of memory immune responses.

Aqueous Extract of Brazilian Berry (Myrciaria jaboticaba) Peel Improves Inflammatory Parameters and Modulates Lactobacillus and Bifidobacterium in Rats with Induced-Colitis.

Natural compounds could be a complementary alternative to inflammatory bowel disease (IBD) management. This study determined the effects of an aqueous extract of Myrciaria jaboticaba peel (EJP) (50 g L-1) on 2,4,6-trinitrobenzenesulfonic acid-induced colitis. Wistar rats were randomized into five groups: HC-healthy control, CC-colitis control, DC-drug control, SJ-short-term treatment with EJP, and LJ-long-term treatment with EJP. The EJP treatments reduced body weight loss, stool consistency score, and spleen enlargement. Gut microbiota was modulated through increased Lactobacillus and Bifidobacterium counts after EJP treatment. Short-chain fatty acids were also higher in the EJP treatment groups. The antioxidant enzyme activities were greater than CC or DC controls. Myeloperoxidase activity (LJ), inducible nitric oxide synthase (LJ/SJ), and intercellular adhesion molecule (SJ) levels were lower than in the CC group. EJP decreased histological scoring, mucosal thickness, and preserved the crypts and histological structure. Therefore, EJP showed beneficial effects and could be potentially used as an adjuvant in IBD treatment.