Gut-microbiome changes may precede celiac disease onset in at-risk children

Reuters Health - 23/07/2021 - Changes in the gut microbiome appear to precede the onset of celiac disease (CD) in at-risk children, a new study suggests.

"We found significant changes in the intestinal microbes, pathways and metabolites as early as 18 months before disease onset," Dr. Maureen M. Leonard of MassGeneral Hospital for Children (MGHfC) in Boston said in a press release. "This was much earlier than we expected."

While CD is the only autoimmune condition with a known trigger (gluten), researchers are still investigating its etiology and pathogenesis.

Dr. Leonard and her colleagues used advanced genomic sequencing techniques to investigate preclinical intestinal changes in 10 children who later developed CD compared with 10 children who did not. The participants took part in the ongoing 500-child prospective CDGEMM study conducted in Italy, Spain and the United States.

Since 2014, CDGEMM has been collecting blood and fecal samples along with environmental data to record intestinal microbiota changes that occur before celiac disease develops. The researchers performed metagenomics analysis on DNA extracted from stool, sequenced the isolated DNA, and conducted taxonomic, functional, and metabolomic profiling of samples.

In cross-sectional analysis at CD onset, the abundance of six microbial strains and several metabolites was different between cases and controls, but there were no differences in microbial species or pathway abundance.

In longitudinal analysis, several microbial species, strains, pathways, and metabolites were detected in increased abundance before CD onset. Among these, Dialister invisus, Parabacteroides sp., Lachnospiraceae, tryptophan metabolism and the metabolites serine and threonine had previously been linked to autoimmune and inflammatory conditions.

By contrast, organisms known to have anti-inflammatory effects, including Streptococcus thermophilus, Faecalibacterium prausnitzii, and Clostridium clostridioforme, were less abundant before CD onset, the researchers report in Proceedings of the National Academy of Sciences of the United States of America.

The researchers also found previously unreported microbes, pathways, and metabolites - including Porphyromonas sp., highmannose-type N-glycan biosynthesis, and serine - that seemed related to CD onset.

"The identified alterations point to a march from the preclinical stage of disease to a break of tolerance to gluten and subsequent onset of CD and may serve as microbial markers of progression toward disease onset," the authors write. "This onset is characterized by complex patterns of increased abundances of proinflammatory species and decreased abundances of protective and anti-inflammatory species at various time points preceding the onset of the disease."

"These microbiome shifts, coupled with metabolome findings, may represent potential biomarkers of CD development," they suggest. "Our study establishes a road map for prospective longitudinal study designs to better understand the role of gut microbiota in disease pathogenesis and therapeutic targets to reestablish tolerance and/or prevent autoimmunity."

The study did not receive commercial funding. Several authors report financial involvements with CosmosID Inc., which sequenced the DNA libraries on its platform, and Inova Diagnostics, which provided ELISA test materials.

SOURCE: https://bit.ly/3BmWDKm Proceedings of the National Academy of Sciences of the United States of America, July 20, 2021.

By Reuters Staff



Posted on 23 July, 20213 August, 2021