Increased Prevalence of Methanosphaera stadtmanae in Inflammatory Bowel Diseases

Abstract

BackgroundThe 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.MethodsTo 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.ResultsMononuclear 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.ConclusionThe prevalence of MSS is increased in IBD patients and is associated with an antigen-specific IgG response.

Differences down-under: alcohol-fueled methanogenesis by archaea present in Australian macropodids

“…Coincidentally, other studies have remarked that there is also a shift from hydrogenotrophic to methylotrophic methanogens under such conditions, as well as in patients suffering from inflammatory bowel diseases (Blais Lecours et al, 2014).…”

Nature vs. Nurture: The Gut Microbiome and Genetics in the Development of Gastrointestinal Disease

“…Another archaea, M. stadtmanae, increases levels of tumor necrosis factor (TNF) in vitro and may influence inflammation in IBD. This is evidenced by increased immunoglobulin G (IgG) responses to M. stadtmanae in IBD patients [104]. These archaea may also be influential in colorectal cancer (CRC) where 80% of CRC patients are methane producers and methane production increases with the severity of the cancer; however, it remains to be seen if these archaea have any causative role or whether they are merely better suited for the harsher tumor microenvironment than normal intestinal flora and subsequently dominate the microbiome in this setting [105,106].…”

Methane matters in animals and man: from beginning to end

“…stadtmanae can be immunostimulatory in animal models of respiratory disease, with the latter provoking a stronger immune response. Furthermore, Blais Lecours et al 30 reported that while the total numbers of methanogenic archaea are less in patients suffering from inflammatory bowel disease (IBD), the prevalence of Msp. stadtmanae was greater in these patients, and healthy human subjects produced an antigen-specific IgG response to this archaeon.…”