Chondroitin Sulfate Flourishes Gut Sulfatase-Secreting Bacteria To Damage Mucus Layers, Leak Bacterial Debris, And Trigger Inflammatory Lesions In Mice

Abstract

Background: An interaction of the food types with the gut microbiota changes is deeply implicated in human health and disease. To verify whether animal-based diets would lead to gut dysbiosis, systemic inflammation and inflammatory pathogenesis, we fed mice with chondroitin sulfate (CS), a sulfate-containing O-glycan naturally occurring in livestock and poultry products, and monitored the dynamic changes of microbial flores, inflammatory signatures, and pathogenic hallmarks. Results: A metagenomic gut microbiota analysis revealed the overgrowth of sulfatasesecreting bacteria and sulfate-reducing bacteria in the gastrointestinal tracts of mice upon daily CS feeding. Sulfatase-secreting bacteria compromise gut integrity through prompting mucin degradation and mucus lesions, which were evident from the upregulation of secretary leukocyte protease inhibitor (SLPI) and mucin 1/4 (MUC-1/4). A synchronous elevation of lipopolysaccharide (LPS) and tumor necrosis factor α (TNF-α) levels in the serum as well as cerebral, hepatic, cardiac and muscular tissues suggests bacterial endotoxinemia, chronic low-grade inflammation and mitochondrial dysfunction, eventually leading to the onset of global inflammatory pathogenesis towards arthritis, dementia, tumor, and fatty liver. Conclusions: CS triggers the early-phase and multi-systemic pathogenesis like arthritis, dementia, tumor, and fatty liver by enhancing gut opportunistic infection and evoking low-grade inflammation in mice. A plausible reason for the inconsistency of CS in treatment of osteoarthritis (OA) was also discussed.

Molecular Characterization of Circulating Microbiome Signatures in Rheumatoid Arthritis

“…Shewanella and Halomonas along with other bacteria to be increased in the gut microbiome of mice fed with chondroitin sulfate. This has been associated with gut inflammation as well as joint inflammation, leading to the hypothesis that the change in the gut microbiome contributes to the proinflammatory state (Liao et al, 2017). Despite other studies identifying this genus as a potential contaminant, we found no evidence of such in our negative control reactions.…”

Effects of Rich-Polyphenols Extract of Dendrobium loddigesii on Anti-Diabetic, Anti-Inflammatory, Anti-Oxidant, and Gut Microbiota Modulation in db/db Mice

“…Monk et al reported that Prevotella and S24–7 are carbohydrate fermenting and short chain fatty acid (SCFA) production bacteria [50]; SCFA can enhance the barrier function of colonic epithelium [51]. Rikenella was sulfatase-secreting bacteria [52], which induced the increase levels of bacterial endotoxinemia and chronic low-grade inflammation [53]. It was suggested that the changes of intestinal flora decreased inflammation and enhanced the mucus/epithelial barrier integrity in DMDJP100 group.…”

Akkermansia muciniphila May Determine Chondroitin Sulfate Ameliorating or Aggravating Osteoarthritis

“…CS.NM with a normal phenotype has more A. muciniphila , but less B. cereus . CS.HL suffering from slight hairless shows no overgrowth of B. cereus and A. muciniphila (Liao et al, 2017b ). Distinct gut microflora communities might be rapidly established in mice fed CS at identical doses and schedules.…”

“…A pro- and anti-inflammatory activities of CS might reflect the temporal and spatial changes of lipopolysaccharide (LPS) content. We previously reported that peripheral (serum and muscle) LPSs declined to normal levels, and that visceral (hepatic and cardiac tissues) LPSs were elevated to maintain a pro-inflammatory state, or adipose and cerebral LPSs declined to maintain an anti-inflammatory state (Liao et al, 2017a , b ). Administration of of a relative high 1.2 mg/kg LPS dose led to anti-inflammatory peritoneal changes, and a relative low 0.25 mg/kg LPS dose caused pro-inflammatory visceral changes, suggesting that anti-LPS treatment reduced LPS in peritoneal but not visceral tissues (Gao et al, 2015 ).…”