Gluten helpful in chronic inflammatory diseases?
In a recent study published in the Journal of Translational Gastroenterology reveals that gluten can cause inflammation and is key in celiac disease. It might also be linked to other autoimmune and inflammatory problems.
Gluten, a key protein found in wheat, barley, and rye, is associated with several health problems, especially celiac disease (CD). It is made up of two main proteins, glutenin and gliadin, with gliadin making up around 70% of gluten and being particularly known for triggering harmful immune reactions in celiac disease. Also, it can cause issues beyond celiac disease, indicating it may play a larger role in inflammatory and autoimmune diseases.
Celiac disease is a long-lasting autoimmune condition marked by inflammation in the intestines, an overactive immune response, and high levels of pro-inflammatory cytokines. Gliadin peptides in gluten are the main triggers for this disease. These peptides cause inflammation in the mucosal lining, damage to the epithelial cells, and disruptions in the balance of gut bacteria.
The negative effects of gluten go beyond celiac disease, impacting various body systems and organs. Gluten peptides can increase gut permeability, letting immune-triggering molecules enter other areas of the body and potentially provoke autoimmune reactions in distant organs. When gliadin peptides reach these organs, they can cause dysfunction and damage through changes that make them more immune-reactive and inflammatory.
This process is believed to play a role in several autoimmune conditions, such as dermatitis herpetiformis, gluten ataxia, gluten allergy, and possibly other non-celiac inflammatory and neurodegenerative disorders.
Recognizing the harmful effects of gluten underscores the importance of thoroughly examining its role in non-celiac autoimmune diseases. Removing gluten from the diet can reduce symptoms in celiac disease and possibly in other chronic inflammatory, metabolic, and autoimmune conditions. Although avoiding gluten might help in these cases, a gluten-free Mediterranean diet is suggested to maintain balanced nutrition.
Reference: Lerner, A., et al. (2024). Gluten is a Proinflammatory Inducer of Autoimmunity. Journal of Translational Gastroenterology. doi.org/10.14218/jtg.2023.00060.
How Macrophage Types Influence the Development of Fatty Liver Disease ?
A new paper published in the journal Proceedings of National Academy of Sciences (PNAS) has revealed the intricate interaction between damaged liver cells and macrophages—a type of white blood cell responsible for eliminating harmful cells and pathogens as well as promoting normal healing.
Nonalcoholic steatohepatitis also called as metabolic dysfunction-associated steatohepatitis (MASH) is an inflammatory liver disease marked by liver scarring or fibrosis that gradually affects liver function. It significantly increases the risk of cirrhosis and liver cancer. With few treatment options available, metabolic dysfunction-associated steatohepatitis is the second leading cause of liver transplants in the United States, following cirrhosis due to chronic hepatitis C infection.
The researchers discovered that the diverse types of macrophages associated with metabolic dysfunction-associated steatohepatitis varied depending on whether the disease was worsening or improving. Crucially, they pinpointed specific macrophage subpopulations essential for addressing metabolic dysfunction-associated steatohepatitis and liver fibrosis, where scar tissue builds up and hampers the liver’s ability to function or heal. These fibrotic tissues obstruct blood flow, putting the entire organ at risk.
Looking ahead, the scientists suggest that a TREM2 agonist—a drug or substance that mimics TREM2’s effects—could be helpful in treating metabolic dysfunction-associated steatohepatitis and fibrosis. It may aid in reversing metabolic dysfunction-associated steatohepatitis and fibrosis, especially when combined with lifestyle changes, weight loss, or bariatric surgery.
Reference: Ganguly S, Rosenthal SB, Ishizuka K, Troutman TD, Rohm TV, Khader N, Aleman-Muench G, Sano Y, Archilei S, Soroosh P, Olefsky JM, Feldstein AE, Kisseleva T, Loomba R, Glass CK, Brenner DA, Dhar D. Lipid-associated macrophages’ promotion of fibrosis resolution during MASH regression requires TREM2. Proc Natl Acad Sci U S A. 2024 Aug 27;121(35):e2405746121. doi: 10.1073/pnas.2405746121. Epub 2024 Aug 22. PMID: 39172787.
Can cancer drugs transform Alzheimer’s care?
The study published in the journal Science proposes that inhibiting the kynurenine pathway—a key regulator of brain metabolism—could enhance or even restore cognitive function in Alzheimer’s disease by restoring normal brain metabolism.
Neuroscientists believe that Alzheimer’s disease might damage brain function by interfering with glucose metabolism, which is essential for maintaining a healthy brain. Essentially, reduced metabolism deprives the brain of the energy it needs, leading to problems with thinking and memory.
A team of neuroscientists has focused on the kynurenine pathway, a key regulator of brain metabolism. They suspect that this pathway is overactivated due to the buildup of amyloid plaques and tau proteins in the brains of Alzheimer’s patients. Researchers have demonstrated that blocking the kynurenine pathway in lab mice with Alzheimer’s Disease can enhance or even restore cognitive function by reestablishing normal brain metabolism.
In the brain, kynurenine plays a role in producing lactate, an energy molecule that supports neurons and maintains healthy synapses. Scientists focused on the enzyme indoleamine-2,3-dioxygenase 1 (IDO1), which produces kynurenine. They hypothesized that elevated levels of IDO1 and kynurenine, driven by the buildup of amyloid and tau proteins, would disrupt normal brain metabolism and cause cognitive decline. By inhibiting IDO1 and thus reducing kynurenine production, they found that the ability of astrocytes to supply neurons with lactate was restored.
indoleamine-2,3-dioxygenase 1 is well-established in oncology, and there are already drugs undergoing clinical trials to inhibit indoleamine-2,3-dioxygenase 1 activity and reduce kynurenine production. This allowed scientists to bypass the lengthy process of developing new drugs and start testing existing ones in lab mice right away.
The next step for scientists is to evaluate indoleamine-2,3-dioxygenase 1 inhibitors in human Alzheimer’s patients to determine if they lead to similar improvements in cognition and memory. Previous clinical trials focused on the use of indoleamine-2,3-dioxygenase 1 inhibitors for cancer treatment did not assess or expect any effects on cognitive function.
Scientists are looking forward to exploring IDO1 inhibitors in upcoming human trials specifically for Alzheimer’s disease.
Reference: Paras S. Minhas et al., Restoring hippocampal glucose metabolism rescues cognition across Alzheimer’s diseasepathologies.Science385,eabm6131(2024).DOI:10.1126/science.abm6131
The Role of Fecal, Blood, and Urinary Biomarkers in Diagnosing inflammatory bowel diseases
A recent study published in the Journal of Translational Gastroenterology reveals that fecal calprotectin and C-reactive protein are key biomarkers in inflammatory bowel disease (IBD) research, demonstrating a strong correlation with disease activity and treatment response.
The global prevalence of inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is increasing.. These conditions mainly impact older populations and show significant geographical variation, with more frequent occurrences in highly developed countries.
At present, ileo-colonoscopy is considered the gold standard for diagnosing and monitoring inflammatory bowel disease. However, this method is invasive and often has limited availability, resulting in extended waiting times for patients.
Recent studies have concentrated on creating biomarkers to evaluate disease activity, forecast disease progression, and track treatment response in IBD patients. Notable biomarkers under investigation include faecal calprotectin (FC) and C-reactive protein (CRP).
Fecal Calprotectin (FC) is a stable protein that remains in faeces for up to a week, making it an excellent marker for non-invasive monitoring. Extensive research on faecal calprotectin in inflammatory bowel disease has demonstrated a strong correlation with endoscopic, histologic, and transmural disease activity.
Where as C-reactive protein (CRP) is an acute-phase reactant produced by the liver in response to inflammation. Its levels frequently rise in inflammatory bowel disease patients, especially during the active phases of the disease. C-reactive protein is utilized as a biomarker to assess disease activity and anticipate treatment response.
Research has investigated the benefits of using multi-target tools that integrate serum and fecal biomarkers with clinical activity indexes. These tools are designed to improve diagnostic and monitoring accuracy by offering a more detailed view of disease status.
While markers such as faecal lactoferrin, autoantibodies, microRNAs, gene expression, and other serological and faecal indicators have shown promising potential, they need further validation before they can be widely used in clinical settings.
Reference: Bencardino, S., D’Amico, F., Zilli, A., Parigi, T. L., Allocca, M., Fiorino, G., Danese, S., & Furfaro, F. (2024). Fecal, blood, and urinary biomarkers in inflammatory bowel diseases. Journal of Translational Gastroenterology, 10.14218/JTG.2024.00001. https://doi.org/10.14218/JTG.2024.00001
