Analysis of gut microbiota may predict disease severity in Chron’s patients

A recent study suggests that SCFA production is associated with a restoration of intestinal homeostasis and sustained remission in CD patients.
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What is already known
Chron’s disease (CD) is a chronic inflammatory condition of the gastrointestinal tract, characterized by an imbalance of gut microbiota with an overall loss of microbiota diversity. CD patients present a broad range of symptoms and frequent relapses after periods of remission. However, how the inter-patients heterogeneity of symptoms and the evolution of the disease are associated with microbiota heterogeneity is still unclear.

What this research adds
Researchers investigated the heterogeneity of gut microbiota of CD patients and identified three distinct groups of microbiota profiles (G1, G2, G3). They also analyzed multiple temporal fecal samples and found that microbiota profiles were associated with increasing symptom severity. Finally, ‘key microbial signature’ of symptom was identified. Main signs of aggravation were loss of anti-inflammatory Short‐Chain Fatty Acids (SCFA) producing bacteria and increase of pro-inflammatory bacteria.

The findings indicate an association between gut dysbiosis and symptoms severity in CD patients, suggesting that assessment of dysbiosis in CD patients should be performed for a better evaluation and managment of the disease.

Chron’s disease (CD) is a chronic inflammatory condition characterized by intestinal dysbiosis which could lead to intestinal complications, thereby debilitating patients life. A recent work by Sylvie Buffet-Bataillon and colleagues, linked the worsening of the symptoms to progressive changes of intestinal microbiota in CD patients.

The study, published in Scientific Reports, suggests that assessing patient dysbiosis could help the optimization of treatments.

To characterize the heterogeneity of microbiota in CD patients, researchers at the Université of Rennes, performed fecal microbiota analysis by genomic sequencing of samples from 259 CD patients

CD patients can be divided into three groups of microbiota profiles 

The researchers identified three distinct subgroups of microbiota profiles, namely G1 (normobiosis), G2 and G3 (dysbiosis). They also observed a progressive decrease of species diversity in the transition from G1 to G3, as well as changes in the proportion of Proteobacteria. 

As reported in other studies, dysbiosis was characterized by reduction in SCFA-producing bacteria of the phylum Firmicutes and increase of Proteobacteria. However, no changes in the calprotectin levels (FC), a standard non-invasive marker for disease activity in CD, were observed.  

Microbiota as marker for CD symptoms severity

To further investigate the dynamics of microbiota profiles over time, researchers analysed consecutive fecal samples provided by a subset of 41 patients and they found an association between microbiota composition and symptoms severity. 

Symptoms severity was found to increase from G1 to G3: G1 profile was associated with cases of remission; G2 with remission and ’mild-moderate’ symptoms; whereas G3 was associated with severe symptoms. Following the samples over time, researchers found that improvement of symptoms was associated either with the stability of the microbiota group or with the transition from G3 to G2, or from G2 to G1. Therefore, transitions could be key indicators of disease evolution over time.

Key microbial signatures could predict changes in CD symptoms over time  

The team then investigated the difference between G1, G2 and G3 profiles and found that the first sign of aggravation (transition from G1 to G2) was due to a loss of the main anti-inflammatory SCFA-producing bacteria Roseburia, Eubacterium, Subdoligranumum, and Ruminococcus. Indeed, it is known that SCFAs promote anti-inflammatory responses of main immune cells in the intestine. They also observed an increase in pro-inflammatory pathogens Proteus and Finegoldia as well as of minor SCFA producers Ezakiella, Anaerococcus, Megasphaera, Anaeroglobus, and Fenollaria

Further aggravation of clinical signs (transition from G2 to G3) was linked to a deeper loss of the minor SCFA-producing bacteria, and to an increase of other pro-inflammatory bacteria such as Klebsiella, Pseudomonas, Salmonella, Acinetobacter, Hafnia and pro-inflammatory Firmicutes Staphylococcus, Enterococcus, and Streptococcus. 

Whether current or future treatments might be able to reverse or stop dysbiosis progression is unknown, but the study suggests that SCFA production is associated with a restoration of intestinal homeostasis and sustained remission in CD patients. Therefore, therapies based on SCFA-producing bacteria could be successful in inducing and maintaining remission of CD or in preventing relapse after surgery.

‘Our data on microbiota changes might provide insight into personalized fecal microbiota transplantation (FMT), which is known to be effective in maintaining remission in CD patients’, scientists say.