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New explanation for autoimmunity: altered pattern of gut microbiota

natasa778

Senior Member
Messages
1,774
Tracing Arthritis to Bugs in the Gut?

The inflamed joints and systemic inflammation characteristic of early rheumatoid arthritis (RA) have been linked with an altered pattern of gut microbial colonization, suggesting a new explanation for autoimmunity and having potential implications for treatment, researchers reported.

Using shotgun gene sequencing, a group of researchers led by Dan L. Littman, MD, PhD, of New York University found that 75% of patients with new-onset, untreated RA had a distinct predominance of intestinal microbiota, with an expansion of pro-inflammatory Prevotella copri.

In contrast, that pattern was only seen in 11.5% of patients with longstanding RA (P<0.01), in 37.5% of those with psoriatic arthritis (P<0.05), and in 21.4% of healthy controls (P<0.01), Littman and colleagues reported online in eLife.

Moreover, individuals with high prevalence of P. copri showed marked reductions in Bacteroides and other species considered beneficial.

...
To explore this, the researchers sequenced specific regions of the relevant 16S gene in 44 fecal samples from patients newly diagnosed with RA who had not yet received any immunosuppressive therapy, along with 26 samples from patients with established RA, 16 samples from patients with psoriatic arthritis, and 28 samples from healthy controls.

In the new-onset group, the samples showed a positive association with two variants of Prevotella and a negative correlation with Bacteroides, Lachnospiraceae, and Clostridia.

The researchers then introduced P. copri into the gastrointestinal tract of mice, and within 2 weeks this organism dominated their gut microbiota, with a loss of protective Bacteroides and Lachnospiraceae.

Those P. copri-colonized mice subsequently were given the colitis-inducing agent dextran sulfate sodium in their drinking water, and developed more severe colitis than mice colonized with Bacteroides, showing greater weight loss and upregulation of interferon gamma.

"These data suggest that a Prevotella-defined microbiome may have the propensity to support inflammation in the context of a genetically susceptible host," Littman and colleagues observed.

A Role for CRP?

They also noted that they initially found it surprising that the prevalence of P. copri in patients with established RA was similar to that in healthy controls.

Possible explanations for this, they suggested, was that the Prevotella-predominant microbiome needs an inflammatory environment to thrive, and with treatment for chronic disease the inflammation has been diminished.

Another possibility is that the change in the gut colonization is a result of an inflammatory factor or process specific to new-onset disease, such as C-reactive Protein (CRP), which binds to bacterial cell walls and upregulates the complement system and macrophage activity.

CRP typically is high in early-phase RA and diminishes with treatment, and also is less characteristic in other autoimmune diseases.

A striking difference was seen in CRP levels in participants in this study, with mean levels of 20.6 mg/L in the new-onset RA group compared with 8.2 mg/L in the established RA patients, 7.6 mg/L in the psoriatic arthritis group, and 1.1 mg/L in healthy controls.

...

Cause or Effect?

In an editorial accompanying the study, Diane Mathis, PhD, of Harvard Medical School pointed out a further area of needed research.

"One critical avenue of study will be to determine whether the association between P. copri and rheumatoid arthritis reflects cause, effect, or co-association," she stated.

The most intriguing possibility is that the association is indeed causative, according to S. Louis Bridges, MD, PhD, of the University of Alabama at Birmingham, who also was not involved in the study.

"We've known for a long time that there are genetic predispositions to these diseases but that there are environmental components as well. So one could posit that this particular type of bacteria is one of -- if not the -- instigating factor that causes the diseases ...
 

knackers323

Senior Member
Messages
1,625
It is said that PWCFS have gut dysbiosis. Anyone know how common this is in those with other autoimmune diseases and healthy people?
 

lansbergen

Senior Member
Messages
2,512
It is said that PWCFS have gut dysbiosis. Anyone know how common this is in those with other autoimmune diseases and healthy people?

Antibiotics and virusinfections can cause it but it should go back to normal when these events are ended.