Long-term maintenance treatment with 300 mg thiamine for fatigue in patients with inflammatory bowel disease: results from an open-label extension of the TARIF study

OBJECTIVE AND AIMS: Fatigue is common in inflammatory bowel disease (IBD). In a RCT we demonstrated reductions in fatigue after 4 weeks' treatment with high-dose oral thiamine. We aimed to investigate whether 300 mg thiamine daily for 12 weeks could maintain the achieved levels of fatigue in patients with IBD after a 4-week intervention with high-dose thiamine; and evaluate the effect of a 6-month period where patients were free to take oral thiamine. METHODS: A randomised, open-label, controlled trial, performed as a long-term extension (LTE) study of an initial randomised, high-dose thiamine trial. Patients were allocated 1:1 to 300 mg oral thiamine or no thiamine for 12 weeks. Subsequently, the patients were allowed to self-treat with over-the-counter (OTC) oral thiamine 6-month. RESULTS: Regardless of allocation in the LTE study fatigue severity increased in the study period. No significant effect of 300 mg oral thiamine were found, when stratifying for initial allocation in the high-dose study or fatigue level at entry in the LTE study. Patients who took OTC thiamine had lower level of fatigue 6 month later (7.8; 95% CI: 5.5-10.1) when compared to the remains (11.0; 95% CI: 9.2-12.8) (p = .02). After the 6-months follow-up without restrictions, 66% of patients had reached normal fatigue levels. CONCLUSIONS: We found no beneficial effect on fatigue from thiamine taken in doses of 300 mg per day for 12 weeks following high-dose treatment. After a 6-months follow-up without restrictions 66% had reached a normal level of fatigue. CLINICAL TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov under study identifier NCT03634735.

The contribution of gut bacterial metabolites in the human immune signaling pathway of non-communicable diseases

The interaction disorder between gut microbiota and its host has been documented in different non-communicable diseases (NCDs) such as metabolic syndrome, neurodegenerative disease, and autoimmune ...

Interactions between gut microbiota and skeletal muscle

The gut microbiota is now recognized as a major contributor to the host’s nutrition, metabolism, immunity, and neurological functions. Imbalanced microbiota (ie, dysbiosis) is linked to undernutrition-induced stunting, inflammatory and metabolic diseases, and cancers. Skeletal muscle also takes part in the interorgan crosstalk regulating substrate metabolism, immunity, and health. Here, we review the reciprocal influence of gut microbiota and skeletal muscle in relation to juvenile growth, performance, aging, and chronic diseases. Several routes involving the vascular system and organs such as the liver and adipose tissue connect the gut microbiota and skeletal muscle, with effects on fitness and health. Therapeutic perspectives arise from the health benefits observed with changes in gut microbiota and muscle activity, further encouraging multimodal therapeutic strategies.

Crohn's And Colitis Support Online | Crohn's And Colitis Social Network - MyCrohnsAndColitisTeam

MyCrohnsAndColitisTeam | The social network and support group for those living with Crohn's and colitis.

Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells

The gut microbial metabolite butyrate is shown to induce the differentiation of colonic T regulatory cells in mice and to ameliorate the development of colitis; it also increases histone H3 acetylation at the Foxp3 promoter.

The gut microbiota in osteoarthritis: where do we stand and what can we do?

Osteoarthritis (OA) is one of the most frequent musculoskeletal diseases characterized by degeneration of articular cartilage, subchondral bone remodeling, and synovial membrane inflammation, which is a leading cause of global disability, morbidity, and decreased quality of life. Interpreting the potential mechanisms of OA pathogenesis is essential for developing novel prevention and disease-modifying therapeutic interventions. Gut microbiota is responsible for a series of metabolic, immunological, and structural and neurological functions, potentially elucidating the heterogeneity of OA phenotypes and individual features. In this narrative review, we summarized research evidence supporting the hypothesis of a “gut-joint axis” and the interaction between gut microbiota and the OA-relevant factors, including age, gender, genetics, metabolism, central nervous system, and joint injury, elucidating the underlying mechanisms of this intricate interaction. In the context, we also speculated the promising manipulation of gut microbiota in OA management, such as exercise and fecal microbiota transplantation (FMT), highlighting the clinical values of gut microbiota. Additionally, future research directions, such as more convincing studies by the interventions of gut microbiota, the gene regulation of host contributing to or attributed to the specific phenotypes of gut microbiota related to OA, and the relevance of distinct cell subgroups to gut microbiota, are expected. Moreover, gut microbiota is also the potential biomarker related to inflammation and gut dysbiosis that is able to predict OA progression and monitor the efficacy of therapeutic intervention.

Regulation of Intestinal Barrier Function by Microbial Metabolites

The human gastrointestinal tract (GI) harbors a diverse population of microbial life that continually shapes host pathophysiological responses. Despite readily available abundant metagenomic data, the functional dynamics of gut microbiota remain to be explored in various health and disease conditions. Microbiota generate a variety of metabolites from dietary products that influence host health and pathophysiological functions. Since gut microbial metabolites are produced in close proximity to gut epithelium, presumably they have significant impact on gut barrier function and immune responses.

Specific inulin‐type fructan fibers protect against autoimmune diabetes by modulating gut immunity, barrier function, and microbiota homeostasis

Scope Dietary fibers capable of modifying gut barrier and microbiota homeostasis affect the progression of type 1 diabetes (T1D). Here, we aim to compare modulatory effects of inulin‐type fructans (ITFs), natural soluble dietary fibers with different degrees of fermentability from chicory root, on T1D development in nonobese diabetic mice. Methods and results Female nonobese diabetic mice were weaned to long‐ and short‐chain ITFs [ITF(l) and ITF(s), 5%] supplemented diet up to 24 weeks. T1D incidence, pancreatic‐gut immune responses, gut barrier function, and microbiota composition were analyzed. ITF(l) but not ITF(s) supplementation dampened the incidence of T1D. ITF(l) promoted modulatory T‐cell responses, as evidenced by increased CD25 + Foxp3 + CD4 + regulatory T cells, decreased IL17A + CD4 + Th17 cells, and modulated cytokine production profile in the pancreas, spleen, and colon. Furthermore, ITF(l) suppressed NOD like receptor protein 3 caspase‐1‐p20‐IL‐1β inflammasome in the colon. Expression of barrier reinforcing tight junction proteins occludin and claudin‐2, antimicrobial peptides β‐defensin‐1, and cathelicidin‐related antimicrobial peptide as well as short‐chain fatty acid production were enhanced by ITF(l). Next‐generation sequencing analysis revealed that ITF(l) enhanced Firmicutes/Bacteroidetes ratio to an antidiabetogenic balance and enriched modulatory Ruminococcaceae and Lactobacilli . Conclusion Our data demonstrate that ITF(l) but not ITF(s) delays the development of T1D via modulation of gut‐pancreatic immunity, barrier function, and microbiota homeostasis.

Activation of Gpr109a, Receptor for Niacin and the Commensal Metabolite Butyrate, Suppresses Colonic Inflammation and Carcinogenesis

Commensal gut microflora and dietary fiber protect against colonic inflammation and colon cancer through unknown targets. Butyrate, a bacterial product from fermentation of dietary fiber in the colon, has been implicated in this process. GPR109A (encoded by Niacr1) is a receptor for butyrate in the colon. GPR109A is also a receptor for niacin, which is also produced by gut microbiota and suppresses intestinal inflammation. Here we showed that Gpr109a signaling promoted anti-inflammatory properties in colonic macrophages and dendritic cells and enabled them to induce differentiation of Treg cells and IL-10-producing T cells.

Gut, inflammation and osteoporosis: basic and clinical concepts

Chronic inflammatory disorders such as inflammatory bowel diseases (IBD) affect bone metabolism and are frequently associated with the presence of osteoporosis. Bone loss is regulated by various mediators of the immune system such as the pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), IL-6, or interferon-gamma. TNF-α, a master cytokine in human IBD, causes bone erosions in experimental models and these effects are exerted by osteoclasts. Other TNF-related cytokines such as receptor activator of nuclear factor kappa B (RANK), its ligand, RANKL, and osteoprotegerin are important mediators in inflammatory processes in the gut and are critically involved in the pathophysiology of bone loss. The awareness and early diagnosis of osteoporosis in states of chronic inflammation, together with applied therapies such as bisphosphonates, may be beneficial in inflammation-associated osteoporosis. Although several mechanisms may contribute to osteoporosis in patients with IBD and coeliac disease, inflammation as an important factor has so far been neglected. As key inflammatory mediators in IBD such as TNF-α are involved in the disease process both in gut and bone, we hypothesise that neutralisation of TNF-α could prove an efficient strategy in the treatment of inflammation-related osteoporosis in the future.

The mycobiome as integral part of the gut microbiome: crucial role of symbiotic fungi in health and disease

The gut mycobiome significantly affects host health and immunity. However, most studies have focused on symbiotic bacteria in the gut microbiome, whereas less attention has been given to symbiotic fungi. Although fungi constitute only 0.01%-0.1% of the gut microbiome, their larger size and unique immunoregulatory functions make them significant. Factors like diet, antimicrobials use, and age can disrupt the fungal community, leading to dysbiosis. Fungal-bacterial-host immune interactions are critical in maintaining gut homeostasis, with fungi playing a role in mediating immune responses such as Th17 cell activation. This review highlights methods for studying gut fungi, the composition and influencing factors of the gut mycobiome, and its potential in therapeutic interventions for intestinal and hepatic diseases. We aim to provide new insights into the underexplored role of gut fungi in human health.

Fecal transplants for autism deliver success in clinical trials

Scientific research continues to uncover interesting connections between the gut microbiome and human health, including everything from depression to PTSD to autoimmune disease. Another example of this are emerging ties between gut health and autism. Exciting new research, now moving to Phase 3 human trials, has found boosting microbial diversity via fecal transplants can dramatically reduce autism symptoms in the long term.

From the gut to the lung: microbiota-associated metabolites as regulators of respiratory immunometabolism

The development and progression of respiratory diseases are influenced by both the local pulmonary microenvironment and the intestinal ecosystem. Research on the gut-lung axis has shown that diverse small-molecule metabolites produced or modified by the gut microbiota can cross the intestinal barrier and enter the systemic circulation, where they may modulate immune-cell response thresholds, functional polarisation, and inflammatory dynamics in the distal lung. The local respiratory microbiota may also contribute to the pulmonary metabolic microenvironment, although its role in metabolite production and immune regulation remains less clearly defined.

A contributory citizen science project reveals the impact of dietary keys to microbiome health in Spain

Low consumption of whole grains, fruits, and vegetables has been identified as dietary risks for non-communicable diseases such as inflammatory bowel diseases (IBDs). We explore how individual and lifestyle factors influence these risks by shaping gut microbiome composition. 1001 healthy participants from all Spanish regions provided personal and dietary data at baseline, six, and twelve months, yielding 2475 responses. Gut microbiome data were analyzed for 500 healthy participants and 321 IBD patients. Our findings reveal that adherence to national dietary guidelines—characterized by diets rich in nuts, seeds, fruits, and vegetables—was associated with greater microbial diversity and reduced IBD-related dysbiosis. Finally, we observed variations in dietary patterns and microbiome diversity and composition across age groups, genders, regions, seasons, and transit time. This study is among the first to uncover dietary intake associated with IBD-related dysbiosis and to propose an interactive website for participants (https://manichanh.vhir.org/POP/en).

Epithelial Barrier Function in Gut-Bone Signaling

The intestinal epithelial barrier plays an essential role in maintaining host homeostasis. The barrier regulates nutrient absorption as well as prevents the invasion of pathogenic bacteria in the host. It is composed of epithelial cells, tight junctions, and a mucus layer. Several factors, such as cytokines, diet, and diseases, can affect this barrier. These factors have been shown to increase intestinal permeability, inflammation, and translocation of pathogenic bacteria. In addition, dysregulation of the epithelial barrier can result in inflammatory diseases such as inflammatory bowel disease. Our lab and others have also shown that barrier disruption can have systemic effects including bone loss. In this chapter, we will discuss the current literature to understand the link between intestinal barrier and bone. We will discuss how inflammation, aging, dysbiosis, and metabolic diseases can affect intestinal barrier-bone link. In addition, we will highlight the current suggested mechanism between intestinal barrier and bone.

Dietary Fiber and Bacterial SCFA Enhance Oral Tolerance and Protect against Food Allergy through Diverse Cellular Pathways

Tan et al. examine the beneficial roles of dietary fiber in peanut allergy using mice. The authors find that this effect involves reshaping of the gut microbiota as well as increased levels of short-chain fatty acids and activity of their receptors GPR43 and GPR109a. High-fiber feeding also increased tolerogenic CD103+ DCs activity, leading to increased Treg cell differentiation.