Effects of Tirzepatide on Gut Microbiota and Gastrointestinal Function After Drug Withdrawal in Obese Patients

Obesity is a global public health crisis, and gut microbiota dysbiosis plays a crucial role in its pathophysiology. Tirzepatide, a dual GIP/GLP-1 receptor agonist, has shown significant weight loss effects, but its impact on the human gut microbiome remains largely unexplored. This observational study aims to fill this gap by characterizing the longitudinal changes in gut microbiota in obese patients undergoing routine Tirzepatide treatment. The investigators will use 16S rRNA V3-V4 region sequencing to analyze microbial diversity and composition (Shannon, Simpson, Chao1 indices, PCoA, LEfSe). Furthermore, The investigators will explore the associations between these microbial shifts and improvements in glucose and lipid metabolism . As secondary and exploratory objectives, gastrointestinal symptoms (GSRS) and gastric emptying function (measured by 13C-octanoic acid breath test) will be monitored during the treatment and withdrawal phases to better understand the overall physiological impact of the treatment.

• Tirzepatide (Drug): Tirzepatide is administered as part of routine clinical care, not assigned by the investigator.

Primary outcomes

• Changes in Gut Microbiota Characteristics [Baseline (0 week) and 3 months]: Assessed by 16S rRNA V3-V4 region sequencing. Includes Alpha diversity (Shannon, Simpson, Chao1), Beta diversity (PCoA), and core differential genera abundance (e.g., Akkermansia, Bacteroides).

Secondary outcomes

• Changes in Fasting Plasma Glucose,, Lipid Profile, and Body Weight [Baseline (0 week) and 3 months]: Assessed by routine fasting blood tests and anthropometric measurements. Metabolic markers include fasting plasma glucose, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, and body weight.
• Change in Gastrointestinal Symptom Rating Scale (GSRS) Score◦ [Baseline (0 week) and 3 months]: Assessed via the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire.
• Change in Gastric Emptying Function [Baseline, 3 months, and 1 week / 1 month after drug withdrawal◦]: Measured by 13C-octanoic acid breath test.

Sex: All, ages: 18 Years to 65 Years, accepts healthy volunteers

Inclusion Criteria:

Normal Weight Control Group:

* Age 18-65 years
* 18.5 <= BMI < 24 kg/m2
* No obesity-related complications
* No diabetes, hypertension, or other metabolic diseases
* No antibiotics, probiotics, or prebiotics in the past 3 months

Obese Treatment Group:

* Age 18-65 years
* BMI >= 30 kg/m2, or BMI >= 27 kg/m2 with at least one obesity-related complication
* Physician-assessed indication for Tirzepatide
* Planned initiation of Tirzepatide as part of routine clinical care
* No antibiotics, probiotics, or prebiotics in the past 3 months

Exclusion Criteria:

* Known inflammatory bowel disease (IBD), intestinal obstruction, or severe gastrointestinal disease
* Gastrointestinal surgery within 6 months
* Severe hepatic or renal impairment (ALT/AST > 3x ULN, eGFR < 30 ml/min/1.73m2)
* History of malignancy
* Severe psychiatric or cognitive disorder
* Pregnancy or lactation
* Acute infection within 1 month
* Any condition deemed unsuitable by the investigator