The gut microbiome contains more than 100 trillion different microorganisms, including bacteria, fungi, viruses and protozoa. Majority of the intestinal bacteria belong to the four phyla including Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria, and in healthy adults Firmicutes and Bacteroidetes are the main ones. A number of studies have confirmed that changes in the structure and abundance of intestinal microbiota play an important biological role, including: immune regulation, nutrition, metabolism and defense against pathogens. The more richness and diversity of microbiota seen as an indicator of good health, while decrease diversity and imbalance in microbiota may be closely related to a large range of diseases, especially in intestinal diseases. Studies have confirmed that disorders of intestinal bacteria are involved in the occurrence and development of intestinal diseases including IBS and IBD. Partial IBD patients in remission may also suffer IBS-like symptoms, which may be related to the intestinal microbiota. However, the results of our cross-sectional study indicate that the onset of IBS might not be related to the obvious alteration in intestinal bacteria. Further analysis revealed that CD patients in remission with IBS-type symptoms might be related to the increase of Faecalibacterium and decrease of Fusobacterium. There was no statistically significant difference in the abundance of intestinal bacteria between the UCR-IBS+ and UCR-IBS- groups at any taxonomic levels. UC patients in remission with IBS-type symptoms cannot be explained by changes in the abundance and structure of intestinal microbiota from our across-sectional study.
Our study found that the proportion of Bacteroidetes in IBS patients at the phylum level was a trend to increase, while the Firmicutes decreases compared with Control subjects, but the difference was not statistically significant. At genus taxonomic, the alterations of bacteria composition in IBS patients were also not apparently differed from control, while this result was not inconsistent with partial previous research. Indeed, the role of fecal microbiota in IBS is still controversial due to different sample source, study population, dietary habitual and environment factors. A recent prospective study by comparing 110 IBS patients and 39 health controls demonstrated that the diversity of fecal microbiota and the number of Prevotella were reduced in IBS patients. A systematic review involving microbiota in IBS revealed that genus Bacteroide were increased in IBS patients compared with controls. As shown in Figure 3B, our results also shown an increase trend of Bacteroide compared with Controls, but failed to achieve statistically significant, this might be explained by different population, sample size. Consistent with our results, one previous study also found that no difference among major phyla or genera between IBS patients and controls.Our results do not support a role for fecal microbiota in the pathogenesis of IBS and correlate with some other studies that reported significantly differences between IBS patients and healthy controls in the composition of fecal microbiota[11, 32]. The discrepancy may be explained by different population, inter-individual variation, and no further classification of IBS. Further large-sample cohort study is needed to confirm the characteristics of the fecal microbiota of IBS patients.
The interaction between the intestinal microbiota and enteric intestinal immune system is the general mechanism of the pathogenesis of IBD, especially in active stage. Previous studies have confirmed that the disease activity of IBD patients is closely related to a decrease of anti-inflammatory bacteria species and an increase of pro-inflammatory bacteria species , as well as the decrease of overall alpha diversity. But some patients in remission of IBD suffer from varying degrees of IBS-like symptoms[34, 35]. Is there any relationship between the intestinal flora of IBD patients with IBS like symptoms and that of IBS patients? Therefore, we focus to explore the alteration of microbiota community and diversity in IBDR patients with IBS-type symptoms. The results indicated that the decreased richness (Chao1 and ACE index) were observed in CDR-IBS- group, while not in CDR-IBS+, UCR-IBS+, UCR-IBS- group compared with controls. Furthermore, there was trend to decrease number of Bacteroidetes and an increase number of Fusobacteria in CDR-IBS+ and CDR-IBS- based on the analysis of phylum taxonomic levels compared with control and IBS group, this might be due to the different disease. For genus taxonomic analysis, the bacteria community of fecal sample from CDR-IBS- exhibited an apparently difference from other groups by a markedly higher numbers of Fusobacterium and increased trend of Escherichia, while lower numbers of Lachnospira and Faecalibaterium compared to that in CDR-IBS+. However, there was no difference in richness and diversity across the CDR-IBS+, CDR-IBS- group, as well as between UCR-IBS+ and UCR-IBS-. A recent study conducted in IBS subjects have shown that Fusobacterium might exacerbate visceral hypersensitivity, which is not consistent with our study. It may be that the study focused on diarrhea predominant-IBS (IBS-D) and we focused on the relationship between IBS symptoms and microbiota during IBD remission. In addition, Faecalibaterium belong to butyrate-producing genera, is elevated in fecal sample of patients with functional bowel disease. In consistent to previous studies, the relative abundance of Faecalibaterium was significantly higher than that in CDR-IBS+ group, indicating the kind of genera might play an important role in formation of IBS-type symptoms. To date, our current results could not draw an insight that there is a possible association between the presence of IBS-type symptoms in CD or UC patients in remission. Therefore, it is impossible to comment on any causal relationship between specific microbiome characteristics and the development of IBS-type symptoms which is consistent with previous study.
Of course, this study has certain limitations. Firstly, it is a cross-sectional study and do not compare the dynamic changes of intestinal bacteria in the development of IBD patients with IBS-type symptoms. Meanwhile, the associated microbiota in mucosa may more accurately reflect the relationship between microbiota and disease, but in our study only fecal microbiota was detected and analyzed. Secondly, IBS is clinically divided into several types, including constipation (IBS-C),diarrhea (IBS-D), or a combination of both (IBS-mixed) according the Rome IV Diagnostic Criteria. The pathogenesis of different types of IBS is somewhat different. However, due to the small sample size in this single center study, no subgroup analysis was performed on the type of confirmed IBS patients, and IBS-type symptoms. In addition, this study used CDAI and Mayo scores to define the active and remission stage of CD and UC respectively, which are not the gold standard for intestinal inflammation. This is a possible reason that our inability to account the significantly alteration of microbiota in CDR-IBS-.
Despite of observation study by our study and previous study which failed to achieve any difference in CDR-IBS-composition and diversity in IBDR patients reporting IBS-type symptoms. However, clinical trials including probiotics and a low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diets have obtained promising results in IBS, indicating the role involving intestinal microbiota[39, 40]. Also, the effect of probiotics and fecal bacteria transplantation (FMT) in the treatment of IBD are multiple beneficial, and no attention is focus to the impact of these treatments on IBD-like symptoms[41, 42].