Accurately Profiling the Changes and Functions of Key Microflora in the Whole Intestinal Microenvironment Based on the Visual Sampling Capsule Endoscopy in Patients With Inflammatory Bowel Disease

Accurately Profiling the Changes and Functions of Key Microflora in the Whole Intestinal Microenvironment Based on the Visual Sampling Capsule Endoscopy in Patients With Inflammatory Bowel Disease

This is a prospective, single-center, observational cohort study that will enroll 250 participants: 50 with active Crohn's disease, 50 with Crohn's disease in remission, 50 with active ulcerative colitis, 50 with ulcerative colitis in remission, and 50 healthy volunteers. Using a novel visual sampling capsule endoscope, intestinal fluid will be collected non-invasively from four intestinal regions: the upper jejunum, the upper ileum, the terminal ileum, and the colon. Saliva and stool samples will also be collected. All samples will be analyzed using 16S rRNA sequencing, metagenomic sequencing, and non-targeted metabolomics. The study aims to characterize the distribution and function of gut microbiota and metabolites across different intestinal regions in patients with inflammatory bowel disease (IBD), to compare active-stage and remission-stage disease, and to compare IBD patients with healthy volunteers, while evaluating the feasibility and safety of the visual sampling capsule endoscope in IBD patients.

The human gut is home to trillions of microorganisms, mainly bacteria, that help digest food, support the immune system, and protect against harmful germs. The composition of the gut microbiota changes along the gastrointestinal tract, and an imbalance in these microbial communities has been linked to many diseases, including inflammatory bowel disease (IBD). To understand how gut bacteria affect IBD, intestinal fluid samples from different regions of the intestine are needed. However, current sampling methods are either invasive, such as tube-based endoscopy, or provide only indirect information, such as stool samples. There is therefore a need for a safe, accurate, and less uncomfortable way to collect intestinal fluid directly from different parts of the small and large intestine.

A new device, the visual sampling capsule endoscope, has been developed to address this need. It is a small pill (11.6 mm x 32 mm, approximately 3.5 g) that the participant swallows. Inside the pill, a tiny camera helps identify the exact position of the capsule in the digestive tract, and a pump system with a 0.65 mL sampling chamber collects a small amount of intestinal fluid when activated by a wireless radio-frequency signal. Each capsule can sample continuously for up to 10 minutes, and a one-way valve seals the sample safely inside. Four capsules are used to collect fluid from four specific locations: the colon, the upper jejunum, the upper ileum, and the terminal ileum. The capsule is passed naturally in the stool and returned to the study team for sample retrieval. Before this study, the capsule was tested in the laboratory and in animals and worked well; it was also tested in 30 healthy volunteers, demonstrating that it is safe and can collect fluid from different parts of the gut without causing harm.

The main goal of this study is to use the sampling capsule to collect intestinal fluid from patients with Crohn's disease and ulcerative colitis, and from healthy volunteers, and to analyze the bacteria and their metabolites in these samples using 16S rRNA sequencing, metagenomic sequencing, and non-targeted metabolomics. The study aims to characterize how the types and functions of gut bacteria differ across intestinal regions in patients with IBD compared with healthy people, and to evaluate the feasibility and safety of the device in this population.

The study plans to enroll 250 people in total: 50 with active Crohn's disease, 50 with Crohn's disease in remission, 50 with active ulcerative colitis, 50 with ulcerative colitis in remission, and 50 healthy volunteers. Participants must be between 18 and 80 years old and must agree to provide stool, saliva, and intestinal fluid samples and to allow storage of these samples for research purposes. Patients with IBD must have a confirmed diagnosis based on endoscopy, histopathology, imaging studies, or comprehensive assessment by a digestive specialist. Healthy volunteers must have no chronic gastrointestinal symptoms, no history of IBD or other chronic gut diseases, and either a normal colonoscopy within the past year or a negative fecal occult blood test with no related symptoms. Individuals who have or might have gastrointestinal obstruction, stricture, or fistula; who have difficulty swallowing; who have cancer or severe heart, kidney, liver, or blood disease; who are pregnant; who have taken antibiotics within the past 3 months; or who have taken part in another clinical trial within the past 3 months are not eligible. Individuals who are unable or unwilling to undergo abdominal surgery if needed are also excluded.

During screening (Day -14 to 0), a study team member will review the participant's medical history and laboratory and imaging results to check eligibility, perform a pregnancy test if applicable, and obtain written informed consent. A standard capsule endoscopy (without the sampling function) will then be performed to check the small intestine for lesions or obstruction. Following the bowel preparation and fasting schedule, the participant will swallow the sampling capsules, and intestinal fluid will be collected from the four regions (colon, upper jejunum, upper ileum, and terminal ileum). Saliva (1-5 mL) and stool (1-5 g) samples will also be collected. All samples will be frozen at -80 degrees Celsius and stored under coded identifiers. After the capsules are passed and returned, the samples will be transported to a specialized laboratory (Shanghai Majorbio Bio-pharm Technology Co., Ltd.) for 16S rRNA sequencing, metagenomic sequencing, and non-targeted metabolomics. The laboratory has agreed to use the samples only for this study and to destroy them afterward according to the applicable rules.

About 14 days after swallowing the capsule, a study team member will call the participant or see them in the clinic to check for any discomfort or problems. The whole study runs from September 2026 to September 2028; for each participant, the total time from screening to the final follow-up call is about 17 days.

As with any capsule endoscopy, there is a very small risk that the capsule could become stuck in a narrowed part of the intestine; if this happens, a procedure or surgery may be needed. For this reason, people with known or suspected blockages are not allowed to join, and a standard capsule test is performed first to reduce this risk. Other possible risks include throat discomfort during swallowing, nausea, and events related to bowel preparation. The study team will monitor participants closely and manage any event appropriately.

Participants may not receive direct medical benefit from joining. However, the information from this study will help doctors understand how gut bacteria change in IBD and may lead to better ways to diagnose, monitor, or treat the disease in the future.

Samples and data will be labeled with a code rather than the participant's name, and only the research team has the key to the code. Any reports or publications will not include names or any information that could identify participants. Participation is voluntary, and participants may leave the study at any time for any reason without affecting their medical care; they may also ask to have their samples destroyed.

The study is led by researchers at Changhai Hospital and is funded by the National Natural Science Foundation of China (grant number 82400777). The study is not funded by a drug company.

Inclusion Criteria

General Inclusion Criteria:

1. Male or female, aged 18 years or older and 80 years or younger;
2. Willing and able to complete the study assessments, including repeated capsule endoscopy examinations and daily records of diet, activity, and defecation;
3. Willing to provide fecal (stool), saliva, and intestinal fluid samples and to consent to long-term storage of the provided samples for research purposes;
4. Willing to avoid vigorous physical activity during participation in this clinical trial;
5. Willing to participate in this clinical trial and to sign the informed consent form.

Inclusion Criteria for Patients with Ulcerative Colitis (UC):

1. Confirmed diagnosis of ulcerative colitis (UC) for at least 3 months during the screening period (Day -14 to 0), confirmed by endoscopic and histological evidence, with a histopathology report (if no report is available, endoscopy and histological examination may be performed at screening);
2. Diagnosis established by at least one of the following clinically accepted methods: endoscopy (e.g., colonoscopy) showing typical UC manifestations; histopathological examination consistent with UC features; imaging studies (e.g., CTE, MRE) showing typical UC changes; or comprehensive assessment by a digestive specialist based on clinical presentation, laboratory tests (e.g., fecal calprotectin, inflammatory markers), and exclusion of infectious enteropathy.

Inclusion Criteria for Patients with Crohn's Disease (CD):

1. Confirmed diagnosis of Crohn's disease (CD) by at least one of the following clinically accepted methods: endoscopy (e.g., colonoscopy) showing typical CD manifestations; histopathological examination consistent with CD features; imaging studies (e.g., CTE, MRE) showing typical CD changes; or comprehensive assessment by a digestive specialist based on clinical presentation, laboratory tests, and exclusion of infectious enteropathy.

Inclusion Criteria for Healthy Subjects:

1. No chronic gastrointestinal symptoms (e.g., abdominal pain, diarrhea, constipation, hematochezia, bloating);
2. No history of inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, or other chronic gastrointestinal disorders;
3. A normal colonoscopy within the past year, or a negative fecal occult blood test with no related symptoms if colonoscopy has not been performed.

If any of the above items is answered "No", the subject cannot enter the study.

Exclusion Criteria:

1. Other gastrointestinal diseases, including gastrointestinal cancer, indeterminate colitis, infectious colitis or colitis with a definite etiology, and toxic megacolon (for the UC cohort, Crohn's disease is also excluded; for the CD cohort, ulcerative colitis is also excluded);
2. Known or suspected gastrointestinal obstruction, stricture, diverticulum, fistula, or perforation;
3. Severe cardiac, pulmonary, or renal insufficiency, liver cirrhosis, hepatic insufficiency, or hematologic diseases;
4. Known or suspected malignant tumors, acute severe illness, or other end-stage diseases, or concomitant diseases with an expected survival of less than 12 months;
5. Any active infection caused by bacteria, viruses, fungi, or other pathogens, or recurrent or chronic infection;
6. Receipt of anti-infective treatment (including antibacterial, antifungal, or antiviral agents) within 3 months before enrollment;
7. Other medications (to be specified);
8. Inability to undergo or refusal to undergo any abdominal surgery (capsule retention cannot be surgically managed);
9. Planned magnetic resonance imaging (MRI) before the capsule endoscope is excreted;
10. Dysphagia;
11. Pregnant or lactating women;
12. Poor general condition and inability to tolerate sampling capsule endoscopy;
13. Any form of active substance abuse or dependence (including drug or alcohol abuse), any unstable physical or mental illness, or any chronic condition that the investigator considers may interfere with the conduct of the study;
14. Participation in another clinical trial within three months, or current participation in another clinical trial;
15. Any other factors that the investigator considers unsuitable for enrollment or that may affect the participant's participation in the study.