Increased prevalence of Methanosphaera stadtmanae in inflammatory bowel diseases.
BACKGROUND
The gut microbiota is associated with the modulation of mucosal immunity and the etiology of inflammatory bowel diseases (IBD). Previous studies focused on the impact of bacterial species on IBD but seldom suspected archaea, which can be a major constituent of intestinal microbiota, to be implicated in the diseases. Recent evidence supports that two main archaeal species found in the digestive system of humans, Methanobrevibacter smithii (MBS) and Methanosphaera stadtmanae (MSS) can have differential immunogenic properties in lungs of mice; with MSS but not MBS being a strong inducer of the inflammatory response. We thus aimed at documenting the immunogenic potential of MBS and MSS in humans and to explore their association with IBD.


METHODS
To validate the immunogenicity of MBS and MSS in humans, peripheral blood mononuclear cells from healthy subjects were stimulated with these two microorganisms and the production of inflammatory cytokine TNF was measured by ELISA. To verify MBS and MSS prevalence in IBD, stool samples from 29 healthy control subjects and 29 patients suffering from IBD were collected for DNA extraction. Plasma was also collected from these subjects to measure antigen-specific IgGs by ELISA. Quantitative PCR was used for bacteria, methanogens, MBS and MSS quantification.


RESULTS
Mononuclear cells stimulated with MSS produced higher concentrations of TNF (39.5 ng/ml) compared to MBS stimulation (9.1 ng/ml). Bacterial concentrations and frequency of MBS-containing stools were similar in both groups. However, the number of stool samples positive for the inflammatory archaea MSS was higher in patients than in controls (47% vs 20%). Importantly, only IBD patients developed a significant anti-MSS IgG response.


CONCLUSIONS
The prevalence of MSS is increased in IBD patients and is associated with an antigen-specific IgG response.
Centre de recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, Québec, Canada.
Pascale
P
Blais Lecours
Centre de recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, Québec, Canada ; Département de médecine, Faculté de médecine, Université Laval, Québec, QC, Canada.
David
D
Marsolais
Centre de recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, Québec, Canada ; Département de médecine, Faculté de médecine, Université Laval, Québec, QC, Canada.
Yvon
Y
Cormier
CSSS Alphonse-Desjardins, Lévis, Québec, Canada.
Marie
M
Berberi
CSSS Alphonse-Desjardins, Lévis, Québec, Canada.
Chantal
C
Haché
CSSS Alphonse-Desjardins, Lévis, Québec, Canada.
Raymond
R
Bourdages
Centre de recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, Québec, Canada ; Département de biochimie, de microbiologie et de bioinformatique, Faculté des sciences et de génie, Université Laval, Québec, Québec, Canada.
Caroline
C
Duchaine
D000328:Adult; D015153:Blotting, Western; D002170:Canada / Q000453:epidemiology; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005243:Feces / Q000382:microbiology*; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000453:epidemiology* / Q000382:microbiology*; D008297:Male; D017013:Methanobacteriaceae / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D015995:Prevalence; D060888:Real-Time Polymerase Chain Reaction
D016207:Cytokines; D004269:DNA, Bacterial