pattismith
Senior Member
- Messages
- 3,946
Front. Cell. Infect. Microbiol., 04 March 2019 | https://doi.org/10.3389/fcimb.2019.00044
Rifaximin Alters Intestinal Microbiota and Prevents Progression of Ankylosing Spondylitis in Mice
Lianjun Yang1†,
Bin Liu1†,
Junchi Zheng1†,
Jincheng Huang2,
Qinghao Zhao1,
Jinshi Liu1,
Zhihai Su1,
Min Wang1,
Zhifei Cui1,
Tingxuan Wang1,
Weicong Zhang1,
Qingchu Li1 and
Hai Lu1*
Rifaximin also changed the gut microbiota composition with increased Bacteroidetes/Firmicutes phylum ratio, as well as selectively promoting some probiotic populations, including Lactobacillales.
Our results suggest that rifaximin suppressed progression of AS and regulated gut microbiota in AS mice. Rifaximin might be useful as a novel treatment for AS.
Introduction
Ankylosing Spondylitis (AS) is a chronic systemic autoinflammatory disease mainly affects sacroiliac joints and axial skeleton. To date, a lack of knowledge regarding the precise molecular mechanisms underlying AS progression limits the ability to halt the progression of this disease. Although human leukocyte antigen B27 (HLA-B27) is estimated to be linked to 90–95% of AS cases (Martín-Esteban et al., 2017), the relationship between HLA-B27 and AS has not been fully elucidated. The cause of AS cannot be fully explained by a genetic predisposition alone, explaining the ongoing need to identify additional predisposing factors. The consensus is that AS is caused by coaction of heredity and environmental factors (Yang et al., 2016).
Changes in the commensal intestinal microbiota has been associated with several autoimmune diseases, including multiple sclerosis (Mestre et al., 2018), inflammatory bowel disease (IBD) (Sheehan et al., 2015), and type 1 diabetes (Meijnikman et al., 2018). Many studies have shown that AS and IBD share similar genetic risk factors and etiopathogeneses (Rashid et al., 2013). Studies based on next-generation sequencing technology, and bioinformatics suggest a significant relationship between the pathogenesis of AS and dysbiosis of intestinal microbiota. Wen et al. (2017) demonstrated that intestinal microflora in AS patients were enriched in Prevotella melaninogenica, Prevotella copri, and Prevotella sp. C561, along with a lower level of Bacteroides spp. In a similar study, in the terminal ileum, AS patients had significantly increased levels of five bacterial families and reduced levels of two bacterial families, when compared to healthy controls (Costello et al., 2014). In animal experiment, HLA-B27 transgenic rats housed in a germ-free environment do not appear features of spondyloarthritis (SpAs). However, HLA-B27 transgenic rats when transferred to a conventional rat colony, these rats appeared AS-like symptoms including colitis and arthritis (Rath et al., 1996). This suggests that intestinal flora takes a critical role in the pathogenesis of AS, and gut microbiota may therefore become a potential target for AS treatment.
Using antibiotics to manipulate gut microbiota may represent a potentially effective treatment option for AS. Previous research has shown that AS patients treated with moxifloxacin, a fourth-generation fluoroquinolone, presented with significantly reduced inflammatory symptoms (Ogrendik, 2007). Rifaximin is a gastrointestinal selective antibiotic that is almost no absorption into the blood with less adverse reaction (Ponziani et al., 2017). Rifaximin acts by inhibiting bacterial DNA-dependent RNA polymerase. While the full effect of rifaximin on gut flora remains limited. Previous studies have shown that rifaximin can alter intestinal flora, inhibit bacterial attachment, prevent intestinal inflammation, and modulate gut barrier function (Xu et al., 2014; Lopetuso et al., 2018). This special feature distinguishes rifaximin from other systemic antibiotics. Most studies up to now have focused on evaluating the effect of rifaximin on gut-liver axis or gut-brain axis (Ponziani, 2015; Wang et al., 2018). However, it is not clear whether orally administered rifaximin can prevent the development of AS by down-regulation of the inflammatory response triggered by gut microbes. In this research, we have evaluated the effects of rifaximin on the severity of AS, inflammatory response, and the changes in intestinal flora. To our knowledge, it is the first study to evaluate the effect of rifaximin on the gut-bone axis in AS.
@ljimbo423
Rifaximin Alters Intestinal Microbiota and Prevents Progression of Ankylosing Spondylitis in Mice
Lianjun Yang1†,
- 1Department of Orthopedic Surgery, Orthopaedic Hospital of Guangdong Province, Academy of Orthopedics of Guangdong Province, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China
- 2Department of Orthopedics, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, China
Rifaximin also changed the gut microbiota composition with increased Bacteroidetes/Firmicutes phylum ratio, as well as selectively promoting some probiotic populations, including Lactobacillales.
Our results suggest that rifaximin suppressed progression of AS and regulated gut microbiota in AS mice. Rifaximin might be useful as a novel treatment for AS.
Introduction
Ankylosing Spondylitis (AS) is a chronic systemic autoinflammatory disease mainly affects sacroiliac joints and axial skeleton. To date, a lack of knowledge regarding the precise molecular mechanisms underlying AS progression limits the ability to halt the progression of this disease. Although human leukocyte antigen B27 (HLA-B27) is estimated to be linked to 90–95% of AS cases (Martín-Esteban et al., 2017), the relationship between HLA-B27 and AS has not been fully elucidated. The cause of AS cannot be fully explained by a genetic predisposition alone, explaining the ongoing need to identify additional predisposing factors. The consensus is that AS is caused by coaction of heredity and environmental factors (Yang et al., 2016).
Changes in the commensal intestinal microbiota has been associated with several autoimmune diseases, including multiple sclerosis (Mestre et al., 2018), inflammatory bowel disease (IBD) (Sheehan et al., 2015), and type 1 diabetes (Meijnikman et al., 2018). Many studies have shown that AS and IBD share similar genetic risk factors and etiopathogeneses (Rashid et al., 2013). Studies based on next-generation sequencing technology, and bioinformatics suggest a significant relationship between the pathogenesis of AS and dysbiosis of intestinal microbiota. Wen et al. (2017) demonstrated that intestinal microflora in AS patients were enriched in Prevotella melaninogenica, Prevotella copri, and Prevotella sp. C561, along with a lower level of Bacteroides spp. In a similar study, in the terminal ileum, AS patients had significantly increased levels of five bacterial families and reduced levels of two bacterial families, when compared to healthy controls (Costello et al., 2014). In animal experiment, HLA-B27 transgenic rats housed in a germ-free environment do not appear features of spondyloarthritis (SpAs). However, HLA-B27 transgenic rats when transferred to a conventional rat colony, these rats appeared AS-like symptoms including colitis and arthritis (Rath et al., 1996). This suggests that intestinal flora takes a critical role in the pathogenesis of AS, and gut microbiota may therefore become a potential target for AS treatment.
Using antibiotics to manipulate gut microbiota may represent a potentially effective treatment option for AS. Previous research has shown that AS patients treated with moxifloxacin, a fourth-generation fluoroquinolone, presented with significantly reduced inflammatory symptoms (Ogrendik, 2007). Rifaximin is a gastrointestinal selective antibiotic that is almost no absorption into the blood with less adverse reaction (Ponziani et al., 2017). Rifaximin acts by inhibiting bacterial DNA-dependent RNA polymerase. While the full effect of rifaximin on gut flora remains limited. Previous studies have shown that rifaximin can alter intestinal flora, inhibit bacterial attachment, prevent intestinal inflammation, and modulate gut barrier function (Xu et al., 2014; Lopetuso et al., 2018). This special feature distinguishes rifaximin from other systemic antibiotics. Most studies up to now have focused on evaluating the effect of rifaximin on gut-liver axis or gut-brain axis (Ponziani, 2015; Wang et al., 2018). However, it is not clear whether orally administered rifaximin can prevent the development of AS by down-regulation of the inflammatory response triggered by gut microbes. In this research, we have evaluated the effects of rifaximin on the severity of AS, inflammatory response, and the changes in intestinal flora. To our knowledge, it is the first study to evaluate the effect of rifaximin on the gut-bone axis in AS.
@ljimbo423