A comparative study of the gut microbiota in immune-mediated inflammatory diseases—does a common dysbiosis exist?

Abstract

BackgroundImmune-mediated inflammatory disease (IMID) represents a substantial health concern. It is widely recognized that IMID patients are at a higher risk for developing secondary inflammation-related conditions. While an ambiguous etiology is common to all IMIDs, in recent years, considerable knowledge has emerged regarding the plausible role of the gut microbiome in IMIDs. This study used 16S rRNA gene amplicon sequencing to compare the gut microbiota of patients with Crohn’s disease (CD; N = 20), ulcerative colitis (UC; N = 19), multiple sclerosis (MS; N = 19), and rheumatoid arthritis (RA; N = 21) versus healthy controls (HC; N = 23). Biological replicates were collected from participants within a 2-month interval. This study aimed to identify common (or unique) taxonomic biomarkers of IMIDs using both differential abundance testing and a machine learning approach.ResultsSignificant microbial community differences between cohorts were observed (pseudo F = 4.56; p = 0.01). Richness and diversity were significantly different between cohorts (pFDR < 0.001) and were lowest in CD while highest in HC. Abundances of Actinomyces, Eggerthella, Clostridium III, Faecalicoccus, and Streptococcus (pFDR < 0.001) were significantly higher in all disease cohorts relative to HC, whereas significantly lower abundances were observed for Gemmiger, Lachnospira, and Sporobacter (pFDR < 0.001). Several taxa were found to be differentially abundant in IMIDs versus HC including significantly higher abundances of Intestinibacter in CD, Bifidobacterium in UC, and unclassified Erysipelotrichaceae in MS and significantly lower abundances of Coprococcus in CD, Dialister in MS, and Roseburia in RA. A machine learning approach to classify disease versus HC was highest for CD (AUC = 0.93 and AUC = 0.95 for OTU and genus features, respectively) followed by MS, RA, and UC. Gemmiger and Faecalicoccus were identified as important features for classification of subjects to CD and HC. In general, features identified by differential abundance testing were consistent with machine learning feature importance.ConclusionsThis study identified several gut microbial taxa with differential abundance patterns common to IMIDs. We also found differentially abundant taxa between IMIDs. These taxa may serve as biomarkers for the detection and diagnosis of IMIDs and suggest there may be a common component to IMID etiology.Electronic supplementary materialThe online version of this article (10.1186/s40168-018-0603-4) contains supplementary material, which is available to authorized users.

Gut microbiome variation is associated to Multiple Sclerosis phenotypic subtypes

“…Third, we observed differences in microbial taxa. Results for Faecalicoccus, 47 Methanobrevibacter, 10,13 Ruminococcus, 16 and Gemmiger 47 confirm previous findings. While Alistipes and Anaerotroncus abundances reflect findings in a PPMS mouse model, 48 we are the first to find these differentially abundant in RRMS.…”

“…Butyricicoccus abundance was lower in MS than in the total HC group, as confirmed in a previous paper 47 . Between‐group analysis suggests an inverse relationship between Butyricicoccus abundance and presumed CNS inflammation in RRMS.…”

“…While Alistipes and Anaerotroncus abundances reflect findings in a PPMS mouse model, 48 we are the first to find these differentially abundant in RRMS. Not in line with other studies, Lactobacillus , 14 Parabacteroides, 14 Sporobacter, 47 and Clostridium cluster IV 13,14 results are possibly explained by different population subtypes, since we also included less inflammatory phenotypes, or confounder control. Olsenella and Roseburia have been described as differentially abundant in other inflammatory conditions 47,49–51 …”

The influence of blood on the human gut microbiome

“…To show the possible importance of considering the presence of blood in stools of patients, we compared the taxa whose abundance vary between our study and four published studies comparing the microbiome of patients suffering from CRC, Crohn's disease, multiple sclerosis, ulcerative colitis and rheumatoid arthritis [22][23][24][25] ( Table 2). All the reported studies have precision that maximally reached the genus level and some of them had different OTUs for the same genus with variations in different directions making it harder to compare precisely.…”

“…Even though many reports have linked dysbiosis of the gut microbiome to the development of colon cancer and other intestinal diseases, none of these reports have, to our knowledge, investigated the effect of intestinal blood on the composition of the microbiome. Most of these studies compared healthy individuals to those that had developed intestinal lesions with no mention of the possible effect of the presence of blood in stool [22][23][24][25]. We hypothesized that the presence of blood in stools without any underlying intestinal lesions or polyps will affect the composition of the microbiome.…”