Search the Community

Celiac.com 06/29/2024 - Celiac disease is an autoimmune disorder where ingesting gluten leads to damage in the small intestine for those genetically predisposed. The standard treatment for celiac disease is a strict gluten-free diet, which, while effective, can be challenging to maintain and does not always completely prevent symptoms or intestinal damage. This has led researchers to explore new therapeutic approaches aimed at improving the lives of those with celiac disease. These novel therapies fall into five main categories: modulating the immune response to gluten, eliminating gluten before it reaches the intestine, inducing gluten tolerance, modulating intestinal permeability, and restoring a healthy gut microbiota. Modulating the Immune Response One promising area of research involves therapies that block the presentation of gluten peptides by HLA-DQ2 and HLA-DQ8, which are gene variants strongly associated with celiac disease. Three therapies in this category show significant promise: TPM502: This therapy uses three gluten-specific antigenic peptides that interact with T-cells associated with the HLA-DQ2.5 gene. A Phase 2a clinical trial is evaluating the safety and effects of TPM502 in adults with celiac disease. This trial is randomized, placebo-controlled, and involves multiple centers. Patients receive two infusions of TPM502 or a placebo, with the dose escalating through four cohorts to determine the optimal dosage. The study aims to monitor safety, tolerability, and pharmacodynamics. KAN-101: Designed to induce gluten tolerance, KAN-101 targets specific receptors in the liver. The study for KAN-101 is a three-part trial that includes an open-label, multiple ascending dose phase, followed by two double-blind, placebo-controlled phases. Part A of the study assesses the safety and tolerability of KAN-101, while Parts B and C focus on the response to gluten challenges and biomarker responses. This therapy has received Fast Track designation by the US Food and Drug Administration, highlighting its potential to address unmet needs in celiac disease treatment. DONQ52: This is a multi-specific antibody targeting HLA-DQ2. The ongoing clinical trial for DONQ52 involves two parts: a single ascending dose phase and a multiple ascending dose phase, both designed to evaluate the safety and tolerability of the drug in patients with well-controlled celiac disease. This trial aims to understand how the drug behaves in the body and its impact on biomarkers related to celiac disease. Eliminating Gluten Before It Reaches the Intestine Another approach is to prevent gluten from reaching the small intestine, thereby avoiding the immune response altogether. This strategy involves enzymes that break down gluten peptides in the stomach before they can cause harm. While specific therapies in this category are not detailed in the study, the concept is based on reducing the exposure of the small intestine to gluten, thereby preventing the autoimmune reaction. Inducing Gluten Tolerance Inducing gluten tolerance aims to retrain the immune system to tolerate gluten without triggering an autoimmune response. KAN-101 is a notable example in this category, as it seeks to create immune tolerance by targeting receptors in the liver. This approach could potentially allow people with celiac disease to consume gluten without adverse effects. Modulating Intestinal Permeability Celiac disease often increases the permeability of the intestinal lining, allowing gluten peptides to enter the bloodstream and trigger an immune response. Therapies that modulate intestinal permeability aim to strengthen the intestinal barrier. By doing so, these treatments can prevent gluten peptides from passing through the intestinal wall and reduce the overall immune response. Restoring Gut Microbiota Balance The gut microbiota plays a crucial role in overall health and immune function. In people with celiac disease, the balance of gut bacteria is often disrupted. Therapies in this category aim to restore a healthy balance of gut microbiota, which could help reduce symptoms and improve gut health. This approach includes the use of probiotics and other microbiota-modulating treatments. Conclusion The development of novel therapies for celiac disease offers hope for improved management and quality of life for those affected. These therapies, which range from immune modulation to restoring gut microbiota, are still in various stages of clinical trials but show promise in addressing the limitations of a gluten-free diet. For individuals with celiac disease, these advances could mean more effective treatment options and a better ability to manage their condition without the strict dietary restrictions currently required. The ongoing research and clinical trials are a crucial step toward finding more comprehensive solutions for celiac disease, potentially transforming the standard of care in the near future. Read more at: medscape.com sciencedirect.com nature.com

Celiac.com 05/29/2023 - Celiac disease is an autoimmune disorder triggered by gluten consumption. While genes and gluten play a significant role in the development of the disease, researchers have started to explore additional factors that contribute to its onset. One intriguing area of study is the gut microbiota, the vast community of microorganisms that reside in our digestive tract. Recent research has suggested that alterations in the gut microbiota may act as an additional risk factor for celiac disease. To shed light on this complex relationship, scientists have embarked on a journey to explore the biogeographic variation and functional pathways of the gut microbiota in individuals with celiac disease. One challenge researchers face is the variability in sampling sites within the digestive system. Celiac disease primarily affects the small intestine, specifically the duodenum. Therefore, understanding the microbiota along different sections of the duodenum and comparing it to fecal samples is crucial for interpreting the findings accurately and gaining mechanistic insight. Comprehensive Study Using 16S rRNA Gene Sequencing To tackle this issue, a team of scientists conducted a comprehensive study using 16S rRNA gene sequencing, a method that allows for the identification and characterization of microbial communities, and predicted gene function using advanced bioinformatics tools. The research team included Marco Constante; Josie Libertucci; Heather J. Galipeau; Jake C. Szamosi; Gaston Rueda; Pedro M. Miranda; Maria Ines Pinto-Sanchez; Carolyn M. Southward; Laura Rossi; Michelle E. Fontes; Fernando G. Chirdo; Michael G. Surette; Premysl Bercik; Alberto Caminero; and Elena F. Verdu. They are variously affiliated with the Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada; and the Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Instituto de Estudios Inmunológicos y Fisiopatológicos, Universidad Nacional de La Plata-National Scientific and Technical Research Council, La Plata, Argentina. Their team collected duodenal biopsies from sections D1, D2, and D3, aspirates, and stool samples from individuals with active celiac disease, as well as healthy controls. They also assessed participants' celiac disease risk genotypes. To delve deeper into the functional impact of the microbiota, the team selected a subset of duodenal samples with similar celiac disease risk genotypes for further analysis, and used to colonize germ-free mice, enabling the study of gluten metabolism. Study Results - Certain Microbes Present in Celiacs The results of the study were intriguing. The composition and predicted function of the gut microbiota in celiac disease were found to be largely determined by the location within the intestine. In the duodenum, but not in stool samples, specific bacterial species, such as Escherichia coli (D1), Prevotella salivae (D2), and Neisseria (D3), were found to be more abundant in individuals with celiac disease compared to healthy controls. Furthermore, the researchers discovered alterations in bacterial protease and peptidase genes, indicating changes in gluten degradation pathways specific to celiac disease. Interestingly, impaired gluten degradation was observed only in mice colonized with microbiota from individuals with celiac disease, further highlighting the role of the microbiota in gluten metabolism. These findings suggest that celiac disease influences the microbial communities in distinct niches within the gut. The researchers also identified novel microbial proteolytic pathways involved in gluten detoxification, which were impaired in individuals with celiac disease but not in healthy controls carrying the celiac disease risk genotype DQ2. This suggests a potential association between these pathways and active inflammation in the duodenum. It is important to note that the study highlights the significance of sampling site as a confounding factor in microbiome research related to celiac disease. Understanding the nuances of the gut microbiota at different locations within the intestine is crucial for accurate interpretation and meaningful conclusions. Conclusions This groundbreaking research opens up new avenues for exploring the complex interplay between the gut microbiota and celiac disease. By identifying specific microbial species and functional pathways associated with the disease, scientists are gaining valuable insights into its mechanisms. Furthermore, these findings provide potential targets for future therapeutic interventions and diagnostic approaches, ultimately improving the lives of individuals living with celiac disease. As our understanding of the intricate relationship between the gut microbiota and celiac disease deepens, we move one step closer to understanding the parameters of the disease, and possibly to develop better approaches to treatment. Stay tuned for more on this and related stories. Read more at Gastroenterology

Celiac.com 03/15/2021 - COVID-19 is mainly a respiratory illness, but there is mounting evidence to indicate that the gut and gut microbiota may play a role in the disease. A team of researchers recently set out to determine if the gut microbiome is linked to disease severity in patients with COVID-19, and whether variations in microbiome composition might resolve with the passing of the SARS-CoV-2 virus. The research team included Yun Kit Yeoh, Tao Zuo; Grace Chung-Yan Lui; Fen Zhang; Qin Liu; Amy YL Li; Arthur CK Chung; Chun Pan Cheung; Eugene YK Tso; Kitty SC Fung; Veronica Chan; Lowell Ling; Gavin Joynt; David Shu-Cheong Hui; Kai Ming Chow; Susanna So Shan Ng; Timothy Chun-Man Li; Rita WY Ng; Terry CF Yip; Grace Lai-Hung Wong; Francis KL Chan; Chun Kwok Wong; Paul KS Chan; and Siew C Ng. To get the answers, the team reviewed blood, stool and patient records from 100 patients with laboratory-confirmed SARS-CoV-2 infection, from two different hospitals. They collected serial stool samples from 27 of the 100 patients up to 30 days after the resolution of SARS-CoV-2. They assessed gut microbiome composition by shotgun sequencing total DNA from stool extraction. They then measured plasma concentrations of inflammatory cytokines and blood markers. Compared with non-COVID-19 patients, those with COVID-19 showed a substantially changed gut microbiome, whether or not they received medication. In COVID-19 patients, a number of gut microbiota with known immunomodulatory potential, such as Faecalibacterium prausnitzii, Eubacterium rectale and bifidobacteria were low, and remained low up to 30 days after Covid-19 abated. In these cases, Covid-19 severity reflected elevated concentrations of inflammatory cytokines and blood markers such as C reactive protein, lactate dehydrogenase, aspartate aminotransferase and gamma-glutamyl transferase. The connections between gut microbiota composition, levels of cytokines and inflammatory markers in patients with COVID-19 suggest that gut microbiota composition reflects disease severity and weakened immune responses. Moreover, because gut microbiota imbalance after Covid-19 resolution may lead to persistent symptoms, it is important to understand how gut microorganisms are involved in inflammation and COVID-19. Read more in Gut The researchers are variously affiliated with the Department of Microbiology, The Chinese University of Hong Kong, Shatin, Hong Kong; the Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong; the Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong; the State Key Laboratory for digestive disease, Institute of Digestive Disease, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Shatin, Hong Kong; the Stanley Ho Centre for Emerging Infectious Diseases, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong Department of Medicine and Geriatrics, United Christian Hospital, Kwun Tong, Hong Kong; the Department of Pathology, United Christian Hospital, Kwun Tong, Hong Kong; the Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Shatin, Hong Kong; the Department of Chemical Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong; the Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong.

Celiac.com 04/16/2018 - A team of researchers recently set out to investigate whether alterations in the developing intestinal microbiota and immune markers precede celiac disease onset in infants with family risk for the disease. The research team included Marta Olivares, Alan W. Walker, Amalia Capilla, Alfonso Benítez-Páez, Francesc Palau, Julian Parkhill, Gemma Castillejo, and Yolanda Sanz. They are variously affiliated with the Microbial Ecology, Nutrition and Health Research Unit, Institute of Agrochemistry and Food Technology, National Research Council (IATA-CSIC), C/Catedrático Agustín Escardin, Paterna, Valencia, Spain; the Gut Health Group, The Rowett Institute, University of Aberdeen, Aberdeen, UK; the Genetics and Molecular Medicine Unit, Institute of Biomedicine of Valencia, National Research Council (IBV-CSIC), Valencia, Spain; the Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire UK; the Hospital Universitari de Sant Joan de Reus, IISPV, URV, Tarragona, Spain; the Center for regenerative medicine, Boston university school of medicine, Boston, USA; and the Institut de Recerca Sant Joan de Déu and CIBERER, Hospital Sant Joan de Déu, Barcelona, Spain The team conducted a nested case-control study out as part of a larger prospective cohort study, which included healthy full-term newborns (> 200) with at least one first relative with biopsy-verified celiac disease. The present study includes 10 cases of celiac disease, along with 10 best-matched controls who did not develop the disease after 5-year follow-up. The researchers profiled fecal microbiota, as assessed by high-throughput 16S rRNA gene amplicon sequencing, along with immune parameters, at 4 and 6 months of age and related to celiac disease onset. The microbiota of infants who remained healthy showed an increase in bacterial diversity over time, especially by increases in microbiota from the Firmicutes families, those who with no increase in bacterial diversity developed celiac disease. Infants who subsequently developed celiac disease showed a significant reduction in sIgA levels over time, while those who remained healthy showed increases in TNF-α correlated to Bifidobacterium spp. Healthy children in the control group showed a greater relative abundance of Bifidobacterium longum, while children who developed celiac disease showed increased levels of Bifidobacterium breve and Enterococcus spp. The data from this study suggest that early changes in gut microbiota in infants with celiac disease risk could influence immune development, and thus increase risk levels for celiac disease. The team is calling for larger studies to confirm their hypothesis. Source: Microbiome. 2018; 6: 36. Published online 2018 Feb 20. doi: 10.1186/s40168-018-0415-6

Celiac.com 03/01/2021 - Although COVID-19 mainly affects the respiratory system, growing evidence indicates that the GI tract also plays a role in the disease. A team of researchers recently set out to determine if the gut microbiome is connected to disease severity in patients with Covid-19, and whether changes in microbiome composition might return to normal with the clearance of the SARS-CoV-2 virus. Here's what they found. The research team included Yun Kit Yeoh; Tao Zuo; Grace Chung-Yan Lui; Fen Zhang; Qin Liu; Amy YL Li; Arthur CK Chung; Chun Pan Cheung; Eugene YK Tso; Kitty SC Fung; Veronica Chan; Lowell Ling; Gavin Joynt; David Shu-Cheong Hui; Kai Ming Chow, Susanna So Shan Ng; Timothy Chun-Man Li; Rita WY Ng; Terry CF Yip; Grace Lai-Hung Wong; Francis KL Chan; Chun Kwok Wong; Paul KS Chan; and Siew C Ng. For their study, the team reviewed blood, stool and data from 100 patients with laboratory-confirmed SARS-CoV-2 infection. They collected serial stool samples from 27 of the 100 patients up to 30 days after clearance of SARS-CoV-2. To assess gut microbiome compositions, they shotgun sequenced total DNA extracted from stools. They measured concentrations of inflammatory cytokines and blood markers from plasma. Compared with non-Covid-19 individuals. Patients with COVID-19 showed substantially changed gut microbiome composition, with or without taking medication. Several gut bacteria with known immunomodulatory potential, such as Faecalibacterium prausnitzii, Eubacterium rectale and bifidobacteria, were significantly reduced in patients and remained low for up to a month after Covid-19 resolution. This altered gut microbiome displayed stratification with disease severity via elevated concentrations of inflammatory cytokines and blood markers such as C reactive protein, lactate dehydrogenase, aspartate aminotransferase and gamma-glutamyl transferase. The connections between gut microbiota levels, cytokines and inflammatory markers in Covid-19 patients indicate that the gut microbiome plays a significant role in Covid-19 severity possibly by modulating host immune responses. The researchers suggest that gut microbiota imbalance after Covid-19 resolution could contribute to ongoing symptoms, making it important to determine the role of gut microorganisms in inflammation and Covid-19. Read more in Gut. The researchers are variously affiliated with the Department of Microbiology, The Chinese University of Hong Kong, Shatin, Hong Kong; the Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong; the Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong; the State Key Laboratory for digestive disease, Institute of Digestive Disease, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Shatin, Hong Kong; the Stanley Ho Centre for Emerging Infectious Diseases, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong; the Department of Medicine and Geriatrics, United Christian Hospital, Kwun Tong, Hong Kong; the Department of Pathology, United Christian Hospital, Kwun Tong, Hong Kong; the Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Shatin, Hong Kong; the Department of Chemical Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong; and the Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong.

Celiac.com 08/11/2020 - Research shows that people with celiac disease have an altered gut microbiota, compared with healthy control subjects. A team of researchers recently set out to evaluate the composition of the microbiota of children at celiac onset, and the connection between bacterial abundances and symptoms. The research team included Anna Rita Di Biase, Giovanni Marasco, Federico Ravaioli, Elton Dajti, Luigi Colecchia, Beatrice Righi, Virginia D'Amico, Davide Festi, Lorenzo Iughetti, and Antonio Colecchia. They are variously affiliated with the Pediatric Unit, Modena University Hospital, Modena, Italy; the Department of Medical and Surgical Sciences, University of Bologna, Italy; and the Gastroenterology Unit of University Hospital Borgo Trento in Verona, Italy. Celiac patients were consecutively enrolled at Pediatric Unit referring for suspected celiac disease. healthy control subjects were also included in the study. Stool and duodenal samples were collected and evaluated by HTF-Microbi.Array. The study team enrolled twenty-one celiac patients and 16 healthy control subjects. A total of twenty-three subjects were female (62%). Duodenal microbiota of celiac patients showed a dominance of Enterobacteriaceae and sub dominance of Bacteroidetes/Streptococcus, while stool microbiota showed a lower abundance of Bacteroides-Prevotella (p=0.013), Akkermansia (p=0.002) and Staphylococcaceae (p=0.001) in celiac patients compared to healthy controls. Patients with abdominal pain showed an increased mean relative abundance of Bacillaceae and Enterobaeriaceae, while celiac patients with diarrhea had reduced mean relative abundance of Clostridium cl. XIVa, Akkermansia, with an increase in Bacillaceae, and Fusobacterium. The team's results show that children with celiac disease have different gut microbiota than healthy non-celiac control subjects, with imbalances in pro-inflammatory microbiota being tied to celiac symptoms. The team calls for further study of the exact connection between gut microbiota and early-onset and symptoms of celiac disease. Learning more about the changes to the gut microbiota of children as they develop celiac disease may offer new paths to diagnosis and treatment in the future. Read more at the J Gastroenterol Hepatol. 2020 Jul 14

Celiac.com 04/27/2020 - Recent studies on celiac disease have reported changes in the gut microbiome. Researchers don't currently know if the change in the microbial makeup is the cause or a result of the disease, especially in cases of adult onset celiac disease. A team of researchers recently set out to compare of small gut and whole gut microbiota of first-degree relatives with adult celiac disease patients and controls. The research team included Rahul Bodkhe, Sudarshan A. Shetty, Dhiraj P. Dhotre, Anil K. Verma, Khushbo Bhatia, Asha Mishra, Gurvinder Kaur, Pranav Pande, Dhinoth K. Bangarusamy, Beena P. Santosh, Rajadurai C. Perumal, Vineet Ahuja, Yogesh S. Shouche, and Govind K. Makharia. They are variously affiliated with the National Centre for Microbial Resource, National Centre for Cell Science, Pune, India; the Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India; the Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi, India; and AgriGenome Labs Pvt. Ltd., Kerala, India. First-degree relatives of celiac patients might offer researchers a chance to study gut microbiome in pre-disease state, since they are genetically prone toward celiac disease. 16S rRNA gene sequencing showed that ecosystem diversity was similar for the disease condition in celiacs, the pre-disease condition in first-degree relatives, and for control subjects. They did note differences in levels of amplicon sequence variant (ASV), indicating changes in specific ASVs between pre-disease and diseased condition. Duodenal biopsies showed greater differences in ASVs compared to fecal samples, which suggests more widespread disturbance to the microbiota in the diseased area. The duodenal microbiota of first-degree relatives was marked by large quantities of ASVs of the genera Parvimonas, Granulicatella, Gemella, Bifidobacterium, Anaerostipes, and Actinomyces. The duodenal microbiota of people with celiac disease contained more ASVs from genera Megasphaera and Helicobacter compared to the microbiota of first-degree relatives. Compared to control group microbiota, the fecal microbiota of both celiacs and first-degree relatives had lower amounts of ASVs classified as Akkermansia and Dorea. Moreover, functional metagenome projections showed reduced gluten degradation by celiac fecal microbiota as compared with first-degree relatives and control subjects. The data show clear differences in ASVs and suggests that celiac fecal microbiota have an impair ability to break down gluten compared to the fecal microbiota of first-degree relatives. More research is needed to examine strain levels and active functional microbiota profiles, in celiacs and first-degree relatives, in order to clarify role of gut microbiome in celiac disease development. Read more in Frontiers of Microbiology, 08 February 2019