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iNature
Both preclinical and confirmed patients with rheumatoid arthritis (RA) exhibit changes
in the gut microbiota.
Prevotella spp.
is preferentially enriched in patients with a class of rheumatoid arthritis
.
On November 2, 2022, Zhang Yu of the Chinese Academy of Medical Sciences/Peking Union Medical College and Liu Zhihua of Tsinghua University jointly published a joint communication entitled "A high-fiber diet synergizes with Prevotella copri and exacerbates" online in Cellular & Molecular Immunology (IF=22).
rheumatoid arthritis", which shows that a high-fiber diet works synergistically with Prevotella copri and exacerbates rheumatoid arthritis
.
The study isolated a strain of Prevotella from the feces of RA patients, P.
copri RA, and showed that colonization of P.
copri RA exacerbated arthritis
in a collagen-induced arthritis (CIA) model.
With the presence of P.
copri RA colonization, a high-fiber diet exacerbates arthritis
through microbial alterations and intestinal inflammation.
Colonization of Pseudomonas aeruginosa in high-fiber feeds is able to digest composite fibers, leading to the overproduction
of organic acids such as fumarate, succinate and short-chain fatty acids.
Succinic acid promotes pro-inflammatory responses in macrophages, and succinic acid supplementation in CIA models exacerbates arthritis
.
In conclusion, the findings highlight the importance of dysbiosis in assessing the impact of dietary interventions on the pathogenesis of RA and provide new insights
into dietary interventions or microbiome changes to improve RA management.
caused by the interaction of genetic and environmental factors.
Genetic studies of individuals with RA have identified multiple risk locus, and a growing body of evidence underscores the critical role
of environmental factors, including microbiota and diet, in the pathogenesis of RA.
Changes in the gut and oral flora have previously been reported to be associated with
new-onset RA.
Prevotella copri is particularly rich
in the gut flora of patients with early-onset RA or preclinical RA compared to the control group.
Intestinal dysregulation can alter the mucosal immune response, which may ultimately contribute to the development of
inflammatory arthritis.
However, the role of Prevotella in regulating the balance between health and disease is complex
.
For example, the high abundance of Prevotella is associated with dietary fiber-induced improvements in sugar metabolism by inducing regulatory T cells (Tregs), which promote glycogen storage and human visceral origin of P.
Prevos.
Hiisticola inhibits arthritis
.
In contrast, patients with RA were enriched with P.
Fecal transplantation of Copri was found to promote a pro-inflammatory Th17 response
to regional lymph nodes in arthritis-prone SKG mice.
Together, these data suggest species- or strain-specific effects
of Prevotella on metabolism or immunomodulation.
The diversity and prevalence of Prevotella species and strains in the human microbiota are influenced by a variety of factors, including lifestyle, diet, and geography
.
In fact, Prevotella is usually enriched in non-Western populations, possibly due to their relatively rich plant-based diet
.
The unique Prevotella outperforms commensal bacteria in terms of polysaccharides by encoding specific carbohydrate-active enzymes (CAZymes), which allows them to reside in the
human gut.
In addition to these differences at the species level, genomic analysis of more than 1,000 P.
copri genomes revealed significant genetic diversity at the strain level, including genes
encoding enzymes that utilize various complex carbohydrates.
In fact, different strains of P.
copri differ in their ability to break down plant polysaccharides and host-derived
mucins.
For example, strains from non-Western subjects showed greater potential for
complex fiber degradation.
A high-fiber diet promotes P.
copri-induced disease severity (Cellular & Molecular Immunology) The consumption of dietary fiber by gut microbes produces organic acids (OAs), particularly short-chain fatty acids (SCFAs).
Fiber fermentation often has a beneficial effect on the host, i.
e.
promoting glucose balance or promoting an anti-inflammatory environment
in the intestine.
For example, succinic acid from dietary fiber fermentation was identified as a substrate for intestinal glycogen production, a process that
maintains glucose balance.
However, these fermentation products can also be harmful in some cases
.
For example, in mice deficient in Toll-like receptor 5 (TLR5), fermentation of dietary soluble fiber by gut microbiota can induce cholestasis, liver inflammation, and liver cancer
.
In addition, in the case of intestinal inflammation, butyrate produced after feed fermentation has been shown to exacerbate inflammation
by increasing NLRP3 activation.
After antibiotic therapy or dyskinesia, microbial succinate has been found to promote Clostridium difficile infection
.
Succinic acid is produced during bacterial fermentation of dietary fiber and has also been reported to be associated with
biological disorders, inflammatory bowel disease patients, and animal models of intestinal inflammation.
Therefore, the effect of microbial fermentation of fiber on host health, mainly influenced by diet, can be environmental dependence and species (strain) dependence
.
RA patients and their doctors are often confused
about what kind of diet patients should follow.
Many studies have shown the effect of
dietary interventions on the development of the disease.
The Mediterranean diet is characterized by a high fiber content, which has been shown to reduce the risk
of cardiovascular disease due to the anti-inflammatory properties of its contents.
As a result, some studies have begun investigating the link between
the Mediterranean diet and a reduced risk of inflammatory diseases such as RA.
However, epidemiological studies have failed to show that the Mediterranean diet reduces the risk or severity of
rheumatoid arthritis.
Interestingly, patients respond greatly to
the Mediterranean diet.
It is not clear whether specific factors, such as gut microbiota, may be contributing to this change
.
Notably, fiber-rich diets produced different immune responses
in individuals with different baseline microbiota.
There are some studies that suggest that a patient's baseline microbiota is associated with response to treatment, but baseline microbiota may also be associated with
dietary response.
Dietary components may interact with microbes if any, but there are few
studies evaluating the combined effects of the two.
Therefore, there is an urgent need to study the combined effects of diet and microorganisms on the pathogenesis or treatment regimen of RA, and these findings will provide a theoretical basis
for modifying the diet to regulate the gut microbiota to improve RA management.
In this study, the authors provide evidence for the first time that the presence of a biological disorder may interfere with the effects of high fiber content in the diet, which in turn exacerbates rheumatoid arthritis
.
The findings may reveal a complex interaction
between biological dysregulation and diet in the management of rheumatoid arthritis.
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The content is 【iNature】
