The Treatment-Naive Microbiome in New-Onset Crohn’s Disease

Abstract

Summary Inflammatory bowel diseases (IBD), including Crohn’s disease (CD), are genetically linked to host pathways that implicate an underlying role for aberrant immune responses to intestinal microbiota. However, patterns of gut microbiome dysbiosis in IBD patients are inconsistent among published studies. Using samples from multiple gastrointestinal locations collected prior to treatment in new-onset cases, we studied the microbiome in the largest pediatric CD cohort to date. An axis defined by an increased abundance in bacteria which include Enterobacteriaceae, Pasteurellacaea, Veillonellaceae, and Fusobacteriaceae, and decreased abundance in Erysipelotrichales, Bacteroidales, and Clostridiales, correlates strongly with disease status. Microbiome comparison between CD patients with and without antibiotic exposure indicates that antibiotic use amplifies the microbial dysbiosis associated with CD. Comparing the microbial signatures between the ileum, rectum, and fecal samples indicates that at this early stage of disease, assessing the rectal mucosa-associated microbiome offers unique potential for convenient and early diagnosis of CD.

Moving beyond microbiome-wide associations to causal microbe identification

“…This outcome provides insight into the clinical observations that the abundance of Lachnospiraceae is inversely correlated to risk of IBD and suggests a causal relationship. Moreover, our findings offer critical preclinical support for use of C. immunis as a probiotic in patients with IBD and lower abundances of Lachnospiraceae 5,13–15 .…”

“…This family of Gram-positive, anaerobic, non-spore-forming bacteria was associated with survival from DSS-induced colitis; its abundance was negligible in MMb mice, intermediate in SPF and co-housed mice, and high in HMb mice (Fig 2F). Interestingly, the Lachnospiraceae have been identified in multiple human studies as inversely correlated with IBD 5,13–15 , although the significance of this association remains unclear.…”

“…These studies typically generate a long list of commensals implicated as biomarkers of disease, with no clear relevance to disease pathogenesis 1–5 . If the field is to move beyond correlations and begin to address causation, an effective system is needed for refining this catalog of differentially abundant microbes and allow for subsequent mechanistic studies 1,4 .…”

The role of inflammation in temporal shifts in the inflammatory bowel disease mucosal microbiome

“…In addition, most studies used faecal samples to characterize the intestinal microbiome and to determine whether there was active inflammation (faecal calprotectin). Faecal specimens do not necessarily reflect the nature of the mucosa-adherent bacteria, 18 nor the degree of inflammation. 19 While the use of faecal calprotectin measurements is useful in the setting of screening for gastrointestinal inflammation, 20 it is not as accurate as endoscopic or histological assessment in patients with IBD, especially those with small bowel inflammation.…”

Ocular Microbiota

“…Changes in microbiology may lead to infection and inflammation (1)(2)(3). The ocular surface includes mucosal surfaces such as bulbar conjunctiva, palpebral conjunctiva, and conjunctival fornices.…”