Prevotella histicola, A Human Gut Commensal, Is as Potent as COPAXONE® in an Animal Model of Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system. We and others have shown that there is enrichment or depletion of some gut bacteria in MS patients compared to healthy controls (HC), suggesting an important role of the gut bacteria in disease pathogenesis. Thus, specific gut bacteria that are lower in abundance in MS patients could be used as a potential treatment option for this disease. In particular, we and others have shown that MS patients have a lower abundance of Prevotella compared to HC, whereas the abundance of Prevotella is increased in patients that receive disease-modifying therapies such as Copaxone® (Glatiramer acetate-GA). This inverse correlation between the severity of MS disease and the abundance of Prevotella suggests its potential for use as a therapeutic option to treat MS. Notably we have previously identified a specific strain , Prevotella histicola ( P. histicola ), that suppresses disease in the animal model of MS, experimental autoimmune encephalomyelitis (EAE) compared with sham treatment. In the present study we analyzed whether the disease suppressing effects of P. histicola synergize with those of the disease-modifying drug Copaxone® to more effectively suppress disease compared to either treatment alone. Treatment with P. histicola was as effective in suppressing disease as treatment with Copaxone®, whereas the combination of P. histicola plus Copaxone® was not more effective than either individual treatment. P. histicola -treated mice had an increased frequency and number of CD4 + FoxP3 + regulatory T cells in periphery as well as gut and a decreased frequency of pro-inflammatory IFN-γ and IL17-producing CD4 T cells in the CNS, suggesting P. histicola suppresses disease by boosting anti-inflammatory immune responses and inhibiting pro-inflammatory immune responses. In conclusion, our study indicates that the human gut commensal P. histicola can suppress disease as efficiently as Copaxone® and may provide an alternative treatment option for MS patients.

Modulation of Pectin on Mucosal Innate Immune Function in Pigs Mediated by Gut Microbiota

“…Other studies have shown an increased abundance of these genera in pigs fed pectin [16]. We also found the increased level of Prevotella with the PEC diet; Prevotella is associated with the consumption of a dietary fiber-rich diet [44] and has been suggested to be an anti-inflammatory microbe in animal gut [45]. Though they were clinically healthy, the CON group exhibited signs of reduced immune tolerance and higher abundances of potential bacterial pathogens in their mucosal tissues, relative to the PEC group.…”

Profiling the Salivary microbiome of the Qatari population

“…Our study divulges the decrease in Co-occurring Prevotella/Porphyromonas shifts in healthy controls and increase in diseased cases. In another study Prevotella histicola was shown to have a boosting effect of Copaxone, used to treat patients with multiple sclerosis [85]. Most of the members of Prevotella remain to be considered as commensals in healthy participants, which then turn to pathogens in oral infections and immunocompromised patients.…”

How oral probiotics affect the severity of an experimental model of progressive multiple sclerosis? Bringing commensal bacteria into the neurodegenerative process

“…On this way, most of studies noticed the induction of IL-10 producing Tregs in the periphery as the main mechanism for EAE protection when mice received many probiotics as Lactobacilli 12 or Prevotella Histicola. 11 The second possibility comes from the different strain of mice used in the models of MS. In EAE models that use SJL/L mice, like we used in the present study, the protective effects against EAE following Lactobacillus helveticus seems to involve decreased IL-6 and reduced Th-17 cells in the spinal cord, without changes in Tregs.…”

“…3 However, other studies reported a therapeutic role of probiotic administration in a variety of EAE models. On this matter, orally administration of Bacteroides fragilis, 9,10 Prevotella histicola, 11 different species of Lactobacillus (L. paracasei plus L. plantarum; 12 L. Reuteri; 13 L. helveticus 14 ), or multi-strain probiotics 15 have demonstrated to improve EAE. In addition, probiotics supplementation to RRMS patients has been shown to modulate immunity by exerting anti-inflammatory effects.…”