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Showing results for tags 'microorganisms'.
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New Study Highlights Role of Gut Microbiota in Celiac Disease
Jefferson Adams posted an article in Latest Research
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- 1 comment
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Celiac.com 01/18/2016 - How come only 2% to 5% of genetically susceptible individuals develop celiac disease? Researchers attempting to answer that question have turned their focus to environmental factors, including gut microorganisms, that may contribute to the development of celiac disease. In a recent study, published in The American Journal of Pathology, researchers using a humanized mouse model of gluten sensitivity found that the gut microbiome can play an important role in the body's response to gluten. Their data show that the rise in overall celiac disease rates over the last 50 years may be driven, at least partly, by variations in gut microbiota. If this proves to be true, then doctors may be able to craft "specific microbiota-based therapies" that "aid in the prevention or treatment of celiac disease in subjects with moderate genetic risk," says lead investigator Elena F. Verdu, MD, PhD, Associate Professor, Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON (Canada). For their study, the team used mice that express the human DQ8 gene, which makes them genetically susceptible to inflammatory responses to gluten, researchers compared immune responses and pathology in the guts of mice that differed in their gut microorganisms. The three groups included germ-free mice, clean–specific-pathogen-free (SPF) mice with microbiota free of opportunistic pathogens and Proteobacteria, and conventional SPF mice that were colonized with a mixture of microorganisms including opportunistic pathogens and Proteobacteria. For example, the microbial profile of conventional SPF mice included Staphylococcus, Streptococcus, and Helicobacter, while the clean SPF had none. Researchers already know that growth and activation of intraepithelial lymphocytes (IELs) is an early sign of celiac disease. This research team saw that gluten treatment led to increased IEL counts in germ-free mice, but not in clean SPF mice. The gluten-induced IEL response in germ-free mice was accompanied by increased cell death in the cells lining the gastrointestinal tract (enterocytes), as well as anatomical changes in the villi lining the small intestine. The germ-free mice also developed antibodies to a component of gluten, known as gliadin, and displayed pro-inflammatory gliadin-specific T-cell responses. A non-gluten protein, zein, did not affect IEL counts, indicating that the response was gluten specific. Meanwhile, the mice colonized with limited opportunistic bacteria (clean SPF), did not develop gluten-induced pathology, compared to germ-free mice or conventional SPF mice with a more diverse microbiota. Interestingly, this protection was suppressed when clean SPF mice were supplemented with an enteroadherent E. coli isolated from a patient with celiac disease. These results are preliminary, and other researchers stress that the specific role of Proteobacteria in celiac disease should not be over interpreted. In an accompanying Commentary, Robin G. Lorenz, MD, PhD, of the Department of Pathology at the University of Alabama at Birmingham, writes that these findings "implicate opportunistic pathogens belonging to the Proteobacteria phylum in celiac disease; however, this does not indicate that Proteobacteria cause celiac disease." Instead, Dr. Lorenz suggests, there may be numerous possible avenues by which Proteobacteria enhance the exposure and immune response to gluten or gliadin. So, the takeaway here is that, while these early results are highly interesting and certainly merit follow-up, it's way too early to say that certain types of gut bacteria may be driving celiac disease, and any types of bacterial treatments that might prevent celiac disease from developing are just the stuff of imagination. Still, this is an important discovery that might pave the way for exactly such types of therapy in the future, so stay tuned. Source: The American Journal of Pathology
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