How the Gut Microbiome Shapes Celiac Disease Risk (+Video)

Celiac.com 12/25/2025 - Celiac disease is an intestinal condition triggered when genetically susceptible people eat foods that contain gluten. Gluten is a group of proteins found in wheat, barley, and rye. Although genes and gluten exposure are both needed for the disease to develop, not everyone who has the risk genes becomes sick. This has led scientists to explore other contributors, especially those involving the digestive system and the microorganisms living inside the intestine. Recent research suggests that the gut environment plays an important part in determining whether a person with the necessary genes will eventually develop the disease.

The study summarized here examined Chinese adults living in Xinjiang who were diagnosed with celiac disease and then compared them with healthy adults of similar age, sex, and ethnic background. The goal was to look deeply at the microorganisms living in their digestive systems and the chemical by-products found in their stool. By analyzing these patterns together, the researchers hoped to identify a clearer explanation of why some individuals develop celiac disease while others with the same genes do not.

How the Study Was Conducted

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The research team collected stool samples from forty adults with celiac disease and forty healthy volunteers. All participants had not recently taken antibiotics or probiotic supplements, since these could alter gut microorganisms. Blood samples were also collected to determine whether each participant carried the human leukocyte antigen genes most strongly linked to celiac disease.

The stool samples were analyzed in two major ways. First, the scientists sequenced all digestive microorganisms, including bacteria, viruses, and other microbes, to understand which species were present and in what quantities. Second, they used advanced chemical analysis to identify thousands of small molecules produced during digestion. These molecules can serve as clues to how the body responds to food, inflammation, and changes in the gut environment.

By combining both types of data, the researchers aimed to identify patterns that distinguish people with celiac disease from those without it. They also explored whether those who carry the known celiac disease genes but do not have the condition share any microbial patterns with those who are sick.

Key Findings About Gut Microorganisms

One of the clearest findings in this study was that the diversity of gut microorganisms was lower in people with celiac disease. In other words, the digestive systems of affected individuals had fewer types of helpful bacteria and a greater imbalance among the species that remained. This reduction in diversity can make the intestinal environment more fragile and more prone to inflammation.

When the researchers looked more closely at specific species, they found that several helpful bacteria were consistently reduced in individuals with celiac disease. These included species known for producing short-chain fatty acids, which are important for nourishing intestinal cells, reducing inflammation, and strengthening the intestinal barrier. Lower levels of these bacteria may contribute to the intestinal damage and immune overreaction seen in the disease.

At the same time, certain other bacteria, such as different strains of Escherichia coli, were more abundant in those with the condition. Some strains of this bacterium have been linked to inflammation and may worsen intestinal injury. This suggests that people with celiac disease have both a loss of protective microorganisms and an increase in organisms that may aggravate symptoms.

How Genetics Influences Gut Microorganisms

The researchers next examined whether individuals who carry the highest-risk genes for celiac disease but do not have the disease show distinct gut patterns. They discovered that people who carry these genes do indeed have different gut microorganisms compared to those without the genes, even if they are healthy. This indicates that genetic risk may alter the gut environment long before symptoms begin.

However, among those with the highest-risk genes, the individuals who actually developed celiac disease showed even more pronounced reductions in several beneficial bacterial species. This suggests that the combination of genetic risk and major disruptions to protective microorganisms may help trigger the disease in certain people.

Viral Patterns in the Gut

The study did not examine only bacteria. It also looked at viruses naturally present in the digestive system, many of which infect bacteria rather than humans. The researchers found that the overall viral community differed noticeably between the celiac and healthy groups. Certain viral families were more abundant in those with celiac disease, although the role of these viruses remains unclear. Since viruses can influence which bacteria thrive or decline, these findings add another layer to understanding the condition.

Important Differences in Digestive Chemicals

The chemical analysis revealed more than five thousand different molecules in the stool samples. Many chemicals involved in fat metabolism, hormone production, and inflammation differed between the two groups. More than a thousand chemicals were significantly altered in individuals with celiac disease.

Several of the most important molecules that stood out in this study were related to lipid metabolism, which is the processing of fats in the body. Some chemical compounds were found in much higher amounts, while others were lower. These shifts suggest that celiac disease affects how the body breaks down and uses fats. Disruptions in fat metabolism can influence inflammation, nutrient absorption, and immune activity, all of which are core features of the disease.

The researchers also noted reduced levels of a compound related to vitamin A processing. Vitamin A is essential for maintaining a healthy intestinal barrier and proper immune responses. A shortage of its active form could make the intestine more vulnerable to injury or infection.

Creating Diagnostic Tools Using Microorganisms and Chemicals

Because both the gut microorganism patterns and the chemical profiles were so distinct in celiac disease, the team attempted to build a diagnostic tool using this information. They identified fifteen bacterial species and eight chemical markers that strongly separated the celiac group from the healthy group.

When used together, the chemical markers were especially powerful in distinguishing the two groups, showing promise for future noninvasive testing. A combined model that used both microorganisms and chemicals also performed well, although not as strongly as the chemical-only model. These findings suggest that future stool-based tests may be able to help diagnose celiac disease more accurately and without the need for invasive procedures.

What This Study Means for People with Celiac Disease

This research provides new insight into how celiac disease develops and why only some genetically susceptible people become sick. The findings emphasize that the gut environment plays a major role. People with celiac disease tend to have fewer protective microorganisms, more harmful ones, and major shifts in vital digestive chemicals.

For individuals who already have celiac disease, this work highlights the importance of good gut health and the potential for future treatments aimed at restoring beneficial microorganisms. For those with a family history or known genetic risk, the study suggests that monitoring the gut environment may one day help predict who is most likely to develop the condition.

Most importantly, the study underscores that celiac disease is not only about gluten and genetics. The health of the gut community, including bacteria and viruses, may strongly influence whether the disease begins and how severe it becomes. Future therapies that modify these microorganisms or support healthier intestinal chemistry may offer new ways to manage or even prevent the condition.

Read more at: translational-medicine.biomedcentral.com

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