Intestinal Taxa Abundance and Diversity in Inflammatory Bowel Disease Patients: An Analysis including Covariates and Confounders

Abstract

Intestinal dysbiosis has been widely documented in inflammatory bowel diseases (IBDs) and is thought to influence the onset and perpetuation of gut inflammation. However, it remains unclear whether such bacterial changes rely in part on the modification of an IBD-associated lifestyle (e.g., smoking and physical activity) and diet (e.g., rich in dairy products, cereals, meat and vegetables). In this study, we investigated the impact of these habits, which we defined as confounders and covariates, on the modulation of intestinal taxa abundance and diversity in IBD patients. 16S rRNA gene sequence analysis was performed using genomic DNA extracted from the faecal samples of 52 patients with Crohn’s disease (CD) and 58 with ulcerative colitis (UC), which are the two main types of IBD, as well as 42 healthy controls (HC). A reduced microbial diversity was documented in the IBD patients compared with the HC. Moreover, we identified specific confounders and covariates that influenced the association between some bacterial taxa and disease extent (in UC patients) or behaviour (in CD patients) compared with the HC. In particular, a PERMANOVA stepwise regression identified the variables “age”, “eat yogurt at least four days per week” and “eat dairy products at least 4 days per week” as covariates when comparing the HC and patients affected by ulcerative proctitis (E1), left-sided UC (distal UC) (E2) and extensive UC (pancolitis) (E3). Instead, the variables “age”, “gender”, “eat meat at least four days per week” and “eat bread at least 4 days per week” were considered as covariates when comparing the HC with the CD patients affected by non-stricturing, non-penetrating (B1), stricturing (B2) and penetrating (B3) diseases. Considering such variables, our analysis indicated that the UC extent differentially modulated the abundance of the Bifidobacteriaceae, Rikenellaceae, Christensenellaceae, Marinifilaceae, Desulfovibrionaceae, Lactobacillaceae, Streptococcaceae and Peptostreptococcaceae families, while the CD behaviour influenced the abundance of Christensenellaceae, Marinifilaceae, Rikenellaceae, Ruminococcaceae, Barnesiellaceae and Coriobacteriaceae families. In conclusion, our study indicated that some covariates and confounders related to an IBD-associated lifestyle and dietary habits influenced the intestinal taxa diversity and relative abundance in the CD and UC patients compared with the HC. Indeed, such variables should be identified and excluded from the analysis to characterize the bacterial families whose abundance is directly modulated by IBD status, as well as disease extent or behaviour.

Basal Diet Fed to Recipient Mice Was the Driving Factor for Colitis and Colon Tumorigenesis, despite Fecal Microbiota Transfer from Mice with Severe or Mild Disease

“…Additionally, in a murine colitis model, consumption of a choline-deficient diet led to a decrease in relative abundance of Erysipelotrichaceae [ 72 ]. Moreover, Bifidobacterium appears to increase in abundance during active IBD and has been reported as a predominant genus in the microbiome of Taiwanese IBD patients [ 73 , 74 , 75 , 76 ]. On the other hand, administration of Bifidobacterium longum suppressed development of preneoplastic lesions in mice and appeared to induce expression of tumor-suppressing microRNAs [ 77 ], whereas Bifidobacterium infantis conferred protection against DSS-induced colitis and abnormal immune signaling [ 77 , 78 ].…”

Ulcerative Colitis After Complicated Diverticulitis

“…Although not supported by clear scientific evidence, maintaining a low-fiber diet after an episode of acute diverticulitis may decrease intestinal bacterial diversity, a phenomenon already observed in IBD cases. 11 Together with modifications linked to aging, these changes may therefore represent a perfect background for the persistence of an altered immune response. Finally, a significant role may be played by the Akkermansia muciniphila species.…”

Alteration of pro-carcinogenic gut microbiota is associated with clear cell renal cell carcinoma tumorigenesis

“…According to previous studies, Desulfovibrionaceae was considered to be a type of bacteria that posed health risk due to its positive correlation with intestinal and systematic inflammation (20,21). Moreover, clinical data suggested that the presence of Desulfovibrionaceae was associated with chronic periodontitis, cell death, and inflammatory bowel diseases (22)(23)(24). With regard to Lactobacillus, it has been generally proved to play an essential role in maintaining homeostasis.…”