Mucosa-Associated Faecalibacterium prausnitzii Phylotype Richness Is Reduced in Patients with Inflammatory Bowel Disease

Abstract

dFaecalibacterium prausnitzii depletion in intestinal diseases has been extensively reported, but little is known about intraspecies variability. This work aims to determine if subjects with gastrointestinal disease host mucosa-associated F. prausnitzii populations different from those hosted by healthy individuals. A new species-specific PCR-denaturing gradient gel electrophoresis (PCR-DGGE) method targeting the 16S rRNA gene was developed to fingerprint F. prausnitzii populations in biopsy specimens from 31 healthy control (H) subjects and 36 Crohn's disease (CD), 23 ulcerative colitis (UC), 6 irritable bowel syndrome (IBS), and 22 colorectal cancer (CRC) patients. The richness of F. prausnitzii subtypes was lower in inflammatory bowel disease (IBD) patients than in H subjects. The most prevalent operational taxonomic units (OTUs) consisted of four phylotypes (OTUs with a 99% 16S rRNA gene sequence similarity [OTU99]), which were shared by all groups of patients. Their distribution and the presence of some disease-specific F. prausnitzii phylotypes allowed us to differentiate the populations in IBD and CRC patients from that in H subjects. At the level of a minimum similarity of 97% (OTU97), two phylogroups accounted for 98% of the sequences. Phylogroup I was found in 87% of H subjects but in under 50% of IBD patients (P ‫؍‬ 0.003). In contrast, phylogroup II was detected in >75% of IBD patients and in only 52% of H subjects (P ‫؍‬ 0.005). This study reveals that even though the main members of the F. prausnitzii population are present in both H subjects and individuals with gut diseases, richness is reduced in the latter and an altered phylotype distribution exists between diseases. This approach may serve as a basis for addressing the suitability of F. prausnitzii phylotypes to be quantified as a putative biomarker of disease and depicting the importance of the loss of these subtypes in disease pathogenesis. Metagenomic studies have shown that the human gut microbiota is constituted by a relatively limited number of dominating bacterial phyla. While in healthy adults Bacteroidetes and Firmicutes are the most abundant phyla, Proteobacteria, Verrucomicrobia, Actinobacteria, and Fusobacteria are relatively scarce (1-3). The firmicute Faecalibacterium prausnitzii (Ruminococcaceae) is one of the three most abundant species, representing approximately 6 to 8% of the gut microbial community in healthy subjects, although it can reach up to 20% in some individuals (1,(4)(5)(6)(7)(8)(9)(10)(11). In contrast, depletion of F. prausnitzii has been reported to occur in several pathological disorders (for a review, see reference 12 and references therein), such as Crohn's disease (CD) (12-19), ulcerative colitis (UC) (11,14,15,17,(20)(21)(22)(23)(24)(25)(26), irritable bowel syndrome (IBS) of alternating type (27), colorectal cancer (CRC) (28, 29), and diabetes (30-32).Many studies have shown the potential role of F. prausnitzii in promoting gut health through the secretion of anti-inflammatory compounds, such as butyrate ...

Colonic microbiota is associated with inflammation and host epigenomic alterations in inflammatory bowel disease

“…1a; Supplementary Table 2). An Escherichia/Shigella/Klebsiella RSV was decreasing in abundance with PC1, whereas Faecalibacterium prausnitzii, on the other hand, had seven RSV that were increasing along this axis, supporting previously reported lower diversity of such sub-species in IBD mucosa 2 . Bacteroides dorei were more common for samples with higher PC2 values, while B. vulgatus abundances were higher for samples with lower PC2 values.…”

Sorting and cultivation ofFaecalibacterium prausnitziifrom fecal samples using flow cytometry in anaerobic conditions

“…These differences could partly be explained by the complex phylogeny of the F. prausnitzii species that comprise at least 3 different phylogroups, and the probable existence of closely related species [1, 19, 20] that have not been described so far and that were mistakenly identified as ‘ F. prausnitzii ’ in 16S repertoire studies that provide only limited phylogenetic information at the species level. Relative proportions between the different phylogroups in one same individual seem to vary depending on specific disease condition, with phylogroup IIb strains being depleted in Crohn’s Disease patients [21, 22]. It has consequently been proposed to use these relative abundances as a biomarker of disease condition [23].…”

Deciphering interactions between the gut microbiota and the immune system via microbial cultivation and minimal microbiomes

“…The abundance of this taxa is routinely reduced in the gut microbiome of patients with inflammatory bowel diseases (IBD), particularly during flares (47–49). This decrease is presumably a consequence of an inflammation-driven increase in tissue oxygen tension that creates an environment unfavorable for F. prausnitzii (50, 51).…”

“…The abundance of this taxa is routinely reduced in the gut microbiome of patients with IBD, particularly during flares. [47][48][49] This decrease is presumably a consequence of an inflammation-driven increase in tissue oxygen tension that creates an environment unfavorable for F. prausnitzii. 50,51 However, the lack of F. prausnitzii may actively contribute to the disease process as this organism possesses anti-inflammatory properties and helps maintain epithelial cell integrity.…”