ObjectiveA decade of microbiome studies has linked IBD to an alteration in the gut microbial community of genetically predisposed subjects. However, existing profiles of gut microbiome dysbiosis in adult IBD patients are inconsistent among published studies, and did not allow the identification of microbial signatures for CD and UC. Here, we aimed to compare the faecal microbiome of CD with patients having UC and with non-IBD subjects in a longitudinal study.DesignWe analysed a cohort of 2045 non-IBD and IBD faecal samples from four countries (Spain, Belgium, the UK and Germany), applied a 16S rRNA sequencing approach and analysed a total dataset of 115 million sequences.ResultsIn the Spanish cohort, dysbiosis was found significantly greater in patients with CD than with UC, as shown by a more reduced diversity, a less stable microbial community and eight microbial groups were proposed as a specific microbial signature for CD. Tested against the whole cohort, the signature achieved an overall sensitivity of 80% and a specificity of 94%, 94%, 89% and 91% for the detection of CD versus healthy controls, patients with anorexia, IBS and UC, respectively.ConclusionsAlthough UC and CD share many epidemiologic, immunologic, therapeutic and clinical features, our results showed that they are two distinct subtypes of IBD at the microbiome level. For the first time, we are proposing microbiomarkers to discriminate between CD and non-CD independently of geographical regions.

The pathophysiology of irritable bowel syndrome (IBS) remains unclear. Here we investigated the microbiome of a large cohort of patients to identify specific signatures for IBS subtypes. We examined the microbiome of 113 patients with IBS and 66 healthy controls. A subset of these participants provided two samples one month apart. We analyzed a total of 273 fecal samples, generating more than 20 million 16S rRNA sequences. In patients with IBS, a significantly lower microbial diversity was associated with a lower relative abundance of butyrate-producing bacteria (P = 0.002; q < 0.06), in particular in patients with IBS-D and IBS-M. IBS patients who did not receive any treatment harboured a lower abundance of Methanobacteria compared to healthy controls (P = 0.005; q = 0.05). Furthermore, significant correlations were observed between several bacterial taxa and sensation of flatulence and abdominal pain (P < 0.05). Altogether, our findings showed that IBS-M and IBS-D patients are characterized by a reduction of butyrate producing bacteria, known to improve intestinal barrier function, and a reduction of methane producing microorganisms a major mechanism of hydrogen disposal in the human colon, which could explain excess of abdominal gas in IBS.

Probiotics can modulate gut microbiota, intestinal permeability, and immune response and could therefore improve cognitive dysfunction and help avoid potential consequences, such as falls, in patients with cirrhosis. The aim of this study was to evaluate the effect of a multistrain probiotic on cognitive function, risk of falls, and inflammatory response in patients with cirrhosis. Consecutive outpatients with cirrhosis and cognitive dysfunction (defined by a Psychometric Hepatic Encephalopathy Score [PHES] < −4) and/or falls in the previous year were randomized to receive either a sachet of a high‐concentration multistrain probiotic containing 450 billion bacteria twice daily for 12 weeks or placebo. We evaluated the changes in cognitive function (PHES); risk of falls (Timed Up and Go [TUG] test, gait speed, and incidence of falls); systemic inflammatory response; neutrophil oxidative burst; intestinal barrier integrity (serum fatty acid–binding protein 6 [FABP‐6] and 2 [FABP‐2] and zonulin and urinary claudin‐3); bacterial translocation (lipopolysaccharide‐binding protein [LBP]); and fecal microbiota. Thirty‐six patients were included. Patients treated with the probiotic (n = 18) showed an improvement in the PHES ( P = 0.006), TUG time ( P = 0.015) and gait speed ( P = 0.02), and a trend toward a lower incidence of falls during follow‐up (0% compared with 22.2% in the placebo group [n = 18]; P = 0.10). In the probiotic group, we observed a decrease in C‐reactive protein ( P = 0.01), tumor necrosis factor alpha ( P = 0.01), FABP‐6 ( P = 0.009), and claudin‐3 ( P = 0.002), and an increase in poststimulation neutrophil oxidative burst ( P = 0.002). Conclusion: The multistrain probiotic improved cognitive function, risk of falls, and inflammatory response in patients with cirrhosis and cognitive dysfunction and/or previous falls.

To date, meta-omic approaches use high-throughput sequencing technologies, which produce a huge amount of data, thus challenging modern computers. Here we present MetaTrans, an efficient open-source pipeline to analyze the structure and functions of active microbial communities using the power of multi-threading computers. The pipeline is designed to perform two types of RNA-Seq analyses: taxonomic and gene expression. It performs quality-control assessment, rRNA removal, maps reads against functional databases and also handles differential gene expression analysis. Its efficacy was validated by analyzing data from synthetic mock communities, data from a previous study and data generated from twelve human fecal samples. Compared to an existing web application server, MetaTrans shows more efficiency in terms of runtime (around 2 hours per million of transcripts) and presents adapted tools to compare gene expression levels. It has been tested with a human gut microbiome database but also proposes an option to use a general database in order to analyze other ecosystems. For the installation and use of the pipeline, we provide a detailed guide at the following website (www.metatrans.org).

The progression of cirrhosis is associated with alterations in the composition of the gut microbiome. To assess microbial translocation, we compared the serum microbial composition of patients with and without ascites and characterized the ascitic fluid microbiome using 16S rDNA high-throughput sequencing data. A complex and specific microbial community was detected in the serum and ascitic fluid of patients with cirrhosis but barely detectable in the serum of healthy controls. The serum microbiome of patients with ascites presented higher levels of lipopolysaccharide binding protein, a marker of microbial translocation, associated with higher diversity and relative abundance of Clostridiales and an unknown genus belonging to the Cyanobacteria phylum compared to patients without ascites. The composition of the fecal microbiome was also more altered in patients with than without ascites, confirming previous studies on fecal microbiome. We propose that alteration of the serum and fecal microbiome composition be considered indicators of cirrhosis progression.

Background: Faecal microbiota transplantation (FMT) is a novel potential therapy for inflammatory bowel diseases, but it is poorly characterised. Methods: We evaluated the performance of the mouse and rat as a pre-clinical model for human microbiota engraftment. We then characterised the effect of a single human stool transfer (HST) on a humanised model of DSS-induced colitis. Colonic and faecal microbial communities were analysed using the 16S rRNA approach and clinical manifestations were assessed in a longitudinal setting. Findings: The microbial community of rats showed greater similarity to that of humans, while the microbiome of mice showed less similarity to that of humans. Moreover, rats captured more human microbial species than mice after a single HST. Using the rat model, we showed that HST compensated faecal dysbiosis by restoring alpha-diversity and by increasing the relative abundance of health-related microbial genera. To some extent, HST also modulated the microbial composition of colonic tissue. These faecal and colonic microbial communities alterations led to a relative restoration of colon length, and a significant decrease in both epithelium damage and disease severity. Remarkably, stopping inflammation by removing DSS before HST caused a faster and greater recovery of both microbiome and clinical manifestation features. Interpretation: Our results indicate that the rat outperforms the mouse as a model for human microbiota engraftment and show that the efficacy of HST can be enhanced when inflammation stimulation is withdrawn. Finally, our findings support a new therapeutic strategy based on the use FMT combined with anti-inflammatory drugs.

Background and Aims Intestinal microbiota dysbiosis is implicated in Crohn’s disease [CD] and may play an important role in triggering postoperative disease recurrence [POR]. We prospectively studied faecal and mucosal microbial recolonisation following ileocaecal resection to identify the predictive value of recurrence-related microbiota. Methods Mucosal and/or faecal samples from 121 CD patients undergoing ileocaecal resection were collected at predefined time points before and after surgery. Ileal biopsies were collected from 39 healthy controls. POR was defined by a Rutgeerts score ≥i2b. The microbiota was evaluated by 16S rRNA sequencing. Prediction analysis was performed using C5.0 and Random Forest algorithms. Results The mucosa-associated microbiota in CD patients was characterised by a depletion of butyrate-producing species (false discovery rate [FDR] &lt;0.01) and enrichment of Proteobacteria [FDR = 0.009] and Akkermansia spp. [FDR = 0.02]. Following resection, a mucosal enrichment of Lachnospiraceae [FDR &lt;0.001] was seen in all patients but in POR patients, also Fusobacteriaceae [FDR &lt;0.001] increased compared with baseline. Patients without POR showed a decrease of Streptococcaceae [FDR = 0.003] and Actinomycineae [FDR = 0.06]. The mucosa-associated microbiota profile had good discriminative power to predict POR, and was superior to clinical risk factors. At Month 6, patients experiencing POR had a higher abundance of taxa belonging to Negativicutes [FDR = 0.04] and Fusobacteria [FDR = 0.04] compared with patients without POR. Conclusions Microbiota recolonisation after ileocaecal resection is different between recurrence and non-recurrence patients, with Fusobacteria as the most prominent player driving early POR. These bacteria involved in the early recolonisation and POR represent a promising therapeutic strategy in the prevention of disease recurrence.

The availability of substrates induces an adaptation of the colonic microbiota activity in bacterial metabolism, which produces less gas and associated issues. Clinical trials.gov NCT02618239.