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Thread: Gut microbiome alterations in children with AIS

  1. #1
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    Gut microbiome alterations in children with AIS

    Alterations of the gut microbiome and plasma proteome in Chinese patients with adolescent idiopathic scoliosis.
    November 24, 2018

    Abstract
    The etiology of adolescent idiopathic scoliosis (AIS), the most common rotational deformity of the spine, is still unclear. Emerging evidence suggests that gut microbiota dysbiosis influences musculoskeletal diseases such as arthritis and osteoporosis. However, the alterations of the fecal microbiome in AIS remain unknown. Thus, the current study was conducted to explore the gut microbiota compositions of Chinese AIS patients. Microbiota communities in the feces of 51 AIS patients and 34 age- and sex-matched healthy individuals were investigated using 16S rRNA sequencing. Meanwhile, the changes in the plasma proteome were detected using tandem mass tag (TMT) labeling coupled with liquid chromatography-mass spectrometry (LC-MS). The relationship between gut microbiota and AIS clinical characteristics as well as the correlation between gut microbiota and the changes in plasma proteins were analyzed. The structure of the gut microbiota differed between the AIS and healthy groups, however, the richness was similar. The genera Prevotella, Gelria, and Desulfovibrio were enriched in the feces of AIS patients. In contrast, the abundance of Parasutterella, Tyzzerella, and Phascolarctobacterium was decreased in the AIS group. More remarkably, a positive correlation between the abundance of the fecal genera Prevotella and the Cobb angles of the AIS patients was observed. Moreover, the major differential plasma proteins related to AIS were Fibronectin 1 (FN1), voltage-dependent anion channel 1 (VDAC1), Ras homolog family member A (RHOA), and AHNAK nucleoprotein (AHNAK). Additionally, the positive correlations between fecal Prevotella and the expression of host plasma FN1 as well as the negative relationships between fecal Prevotella and the expression of host VDAC1 and AHNAK were confirmed. Elucidating these differences in the gut microbiota will provide a foundation to improve our understanding of the pathogenesis of AIS and to support potential therapeutic options based on modifying the gut microbiota.

    The new study is in line with earlier research.

    Nutrition as an environmental factor in the etiology of idiopathic scoliosis.
    March - April, 1993

    Discussion
    Nutrition has already been implicated in scoliosis due to rickets, and worldwide there has been an anecdotal association between poor nutrition and IS. In rural South America, Risser is reported to have observed that a large portion of the IS patients were malnourished and consumed more sugar and flour than normal children. Frederich noted the poor nutritional status of European patients, while Stearns found that American IS patients consumed too many carbohydrates and too little protein.

    These observations are supported by two recent studies, one in the Soviet Union and the other in the United States. The Soviet study found that the incidence of IS was 4 times higher in undernourished children than the population of children at large, while the United States study found that IS patients were picky eaters who consumed twice the amount of candy and soda as their unaffected contemporaries. it is noteworthy that the observers who mentioned any particular dietary anomaly, all noted the larger than average consumption of carbohydrates: in particular, simple carbohydrates.
    Last edited by Dingo; 11-28-2018 at 10:59 AM.

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    From the study:
    a positive correlation between the abundance of the fecal genera Prevotella and the Cobb angles of the AIS patients was observed
    Interestingly Prevotella species play a role in arthritis and other bone diseases.

    Article: Gut Microbe, Prevotella copri, Implicated in RA Pathogenesis

    Study: Role of Gut Microbiota in Rheumatoid Arthritis
    Rheumatoid arthritis (RA) is a systemic autoimmune disease, caused by both genetic and environmental factors. Recently, investigators have focused on the gut microbiota, which is thought to be an environmental agent affecting the development of RA. Here we review the evidence from animal and human studies that supports the role of the gut microbiota in RA. We and others have demonstrated that the abundance of Prevotella copri is increased in some early RA. We have also used gnotobiotic experiments to show that dysbiosis in RA patients contributed to the development of Th17 cell-dependent arthritis in intestinal microbiota-humanized SKG mice. On the other hand, Prevotella histicola from human gut microbiota suppressed the development of arthritis. In summary, Prevotella species are involved in the pathogenesis of arthritis.

    Prevotella appear to play a significant role in Osteomyelitis.

    Article: The microbiome and osteomyelitis, an autoinflammatory bone disease

    A recent paper in the journal Nature discusses experiments that provide a link between a certain gut bacteria, diet, and osteomyeltis (an autoinflammatory bone disease). Osteomyelitis occurs when there is a bacterial infection of the bone marrow. It is often treated with antibiotics but sometimes surgery and amputation are necessary.

    In the study, the researchers induced osteomyelitis in a group of mice. They then gave half the mice high fat diets and half the mice low fat diets. They discovered that the mice eating the high fat diets were protected from osteomyelitis and showed little bone inflammation, while those eating a low fat diet developed the disease.

    The discovery that diet could alter the progression of the disease led the researchers to investigate the microbiome of these mice. The mice with low fat diets had higher amounts of Prevotella and lower amounts of Lactobacillus when compared to normal mice. The reverse was true for the high fat diet mice, they had much less Prevotella and much more Lactobacillus in their guts, which better represents the composition in normal mice.

    To further investigate if Prevotella may be causing the disease, the researchers gave antibiotics to the low fat diet mice, which destroyed the Prevotella population, and decreased the symptoms of the disease.

    Finally, the researchers performed microbiome transplants into germ-free mice that were susceptible for osteomyeltis. Any germ-free mouse that received a transplant high in Prevotella and then was fed a low fat diet developed the disease. However, any mouse that received a transplant that was low in Prevotella, even if that mouse was on a low fat diet, did not develop the disease.

    These results show that dietary intake can alter the microbiome and greatly influence osteomyelitis outcomes.
    Last edited by Dingo; 11-28-2018 at 01:17 PM.

  3. #3
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    Prevotella implicated in numerous chronic, inflammatory diseases.

    The immune response to Prevotella bacteria in chronic inflammatory disease.
    August, 2017

    The microbiota plays a central role in human health and disease by shaping immune development, immune responses and metabolism, and by protecting from invading pathogens. Technical advances that allow comprehensive characterization of microbial communities by genetic sequencing have sparked the hunt for disease-modulating bacteria. Emerging studies in humans have linked the increased abundance of Prevotella species at mucosal sites to localized and systemic disease, including periodontitis, bacterial vaginosis, rheumatoid arthritis, metabolic disorders and low-grade systemic inflammation. Intriguingly, Prevotella abundance is reduced within the lung microbiota of patients with asthma and chronic obstructive pulmonary disease. Increased Prevotella abundance is associated with augmented T helper type 17 (Th17) -mediated mucosal inflammation, which is in line with the marked capacity of Prevotella in driving Th17 immune responses in vitro. Studies indicate that Prevotella predominantly activate Toll-like receptor 2, leading to production of Th17-polarizing cytokines by antigen-presenting cells, including interleukin-23 (IL-23) and IL-1. Furthermore, Prevotella stimulate epithelial cells to produce IL-8, IL-6 and CCL20, which can promote mucosal Th17 immune responses and neutrophil recruitment. Prevotella-mediated mucosal inflammation leads to systemic dissemination of inflammatory mediators, bacteria and bacterial products, which in turn may affect systemic disease outcomes. Studies in mice support a causal role of Prevotella as colonization experiments promote clinical and inflammatory features of human disease. When compared with strict commensal bacteria, Prevotella exhibit increased inflammatory properties, as demonstrated by augmented release of inflammatory mediators from immune cells and various stromal cells. These findings indicate that some Prevotella strains may be clinically important pathobionts that can participate in human disease by promoting chronic inflammation.

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