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  1. Lili Shang1,
  2. Tingting Zhang1,
  3. Xiaoli Liu1,
  4. Hui Wang1,
  5. Chong Gao2,
  6. Jinfang Zhao3,
  7. LI Xiao-Feng1,
  8. Huiying Gao1
  1. 1The Second Hospital Of Shanxi Medical University, Rheumatology, Taiyuan, China
  2. 2Brigham and Women’s Hospital, Boston, Pathology, Boston, United States of America
  3. 3Shanxi Medical University, Medical Statistics, Taiyuan, China


Background: Researchers have linked a species of intestinal bacteria to the onset of rheumatoid arthritis. The lactulose breath test detects small intestinal bacterial overgrowth (SIBO) can measure hydrogen and methane produced by intestinal bacteria.

Objectives: To investigate the intestinal flora of patients with autoimmune diseases through a lactulose breath test.

Methods: The study was conducted on 720 cases of autoimmune disease. The hydrogen value was increased by ≥20p.p.m and the methane value increased by ≥10p.p.m in 90 minutes was defined as positive for SIBO. Spearman’s rank correlation analysis was used to determine the association between age and hydrogen values or methane values.

Results: A total of 75% of patients had a positive breath test. Among them, the positive rate of rheumatoid arthritis (RA) patients was 69.4%, systemic lupus erythematosus (SLE) 69%, Sjogren’s syndrome (SS) 79.22%, ankylosing spondylitis (AS) 89.29%, and juvenile arthritis (JIA) 73.33%. In addition, patients with AS had significantly higher hydrogen value than that with RA, SLE, and SS (p <0.05) (Fig. 1). Sex was no statistically significant difference between lactulose breath test results. In female patients, age was positively correlated with hydrogen values (r = 0.151; p = 0.049) and methane values (r = 0.248; p = 0.001); in male patients, age was negatively correlated with hydrogen values (r = -0.367); p=0.006) (Fig. 2).

Conclusion: Patients with autoimmune disease have positive bacterial growth in the small intestine, and hydrogen production is significantly increased in patients with AS, suggesting that hydrogen production in the small intestine may be related to inflammation. In addition, with increasing age of the female, hydrogen and methane produced in the small intestine may increase, with increasing age of the male, small intestine may reduce the production of hydrogen, suggesting a reason why there are more female patients than male in some autoimmune disease.

Figure 1

Differences in hydrogen and methane levels in different autoimmune diseases in the lactose breath test: (A and B) The production of hydrogen in the small intestine of patients with ankylosing spondylitis is significantly higher than that of other autoimmune patients. (C and D) Methane production in the small intestine showed no significant difference between the groups. *P < 0.05; **P < 0.01; ***P < 0.001. RA: rheumatoid arthritis, SLE: systemic lupus erythematosus, SS: Sjogren’s syndrome, AS: ankylosing spondylitis, JIA: juvenile arthritis.

Figure 2

Correlation between the age of autoimmune patients and the hydrogen and methane values in the lactose breath test: (A1-A4) The age of female patients is positively correlated with the production of hydrogen and methane in the small intestine. (B1-B4) The age of male patients is negative related to the production of hydrogen in the small intestine.

References [1] Gislane Lelis Vilela de Oliveira, Aline Zazeri Leite, Bruna Stevanato Higuchi, Marina Ignácio Gonzaga, Vânia Sammartino Mariano.Intestinal dysbiosis and probiotic applications in autoimmune diseases. Immunology. 2017Sep; 152(1): 1–12.doi: 10.1111/imm.12765

[2] Maria C. Opazo, Elizabeth M. Ortega-Rocha, Irenice Coronado-Arrázola, Laura C. Bonifaz, Helene Boudin, Michel Neunlist, Susan M. Bueno, Alexis M. Kalergis, Claudia A. Riedel. Intestinal Microbiota Influences Non-intestinal Related Autoimmune Diseases. Front Microbiol. 2018;9:432.doi: 10.3389/fmicb.2018.00432

Disclosure of Interests: None declared

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