Rectal swabs as a viable alternative to faecal sampling for the analysis of gut microbiota functionality and composition.

Faecal or biopsy samples are frequently used to analyse the gut microbiota, but issues remain with the provision and collection of such samples. Rectal swabs are widely-utilised in clinical practice and previous data demonstrate their potential role in microbiota analyses; however, studies to date have been heterogenous, and there are a particular lack of data concerning the utility of swabs for the analysis of the microbiota's functionality and metabolome. We compared paired stool and rectal swab samples from healthy individuals to investigate whether rectal swabs are a reliable proxy for faecal sampling. There were no significant differences in key alpha and beta diversity measures between swab and faecal samples, and inter-subject variability was preserved. Additionally, no significant differences were demonstrated in abundance of major annotated phyla. Inferred gut functionality using Tax4Fun2 showed excellent correlation between the two sampling techniques (Pearson's coefficient r = 0.9217, P < 0.0001). Proton nuclear magnetic resonance (1H NMR) spectroscopy enabled the detection of 20 metabolites, with overall excellent correlation identified between rectal swab and faecal samples for levels all metabolites collectively, although more variable degrees of association between swab and stool for levels of individual metabolites. These data support the utility of rectal swabs in both compositional and functional analyses of the gut microbiota.

Comparative effectiveness of a second-line biologic in patients with ulcerative colitis: vedolizumab followed by an anti-TNF versus anti-TNF followed by vedolizumab.

Background: Sequential drug treatment with biological agents in ulcerative colitis (UC) is becoming increasingly complex. There are few studies comparing head-to-head outcomes in second-line treatments. The study assesses whether using anti-tumour necrosis factor (anti-TNF)-α therapy following the α4ß7 integrin blocker vedolizumab (VDZ) or VDZ after an anti-TNF has more favourable clinical outcomes in UC in a real-world outpatient setting. Methods: Patients with UC who were exposed to first-line anti-TNF (adalimumab or infliximab) or VDZ who subsequently switched to the alternate class between May 2013 and August 2020 were identified by reviewing patient databases at 10 hospitals. Data were collected retrospectively using patient records. Baseline demographics, disease activity indices, biochemical markers, endoscopic Mayo score, colectomy rates, treatment persistence and urgent hospital utilisation composite endpoint (UHUC) rates were examined over a 52-week period. Results: Second-line week 52 treatment persistence was higher in the VDZ group (71/81, 89%) versus the anti-TNF group (15/34, 44%; p=0.0001), as were week 52 colectomy-free survival (VDZ: 77/80, 96%, vs anti-TNF: 26/32, 81%; p=0.009), week 52 UHUC survival (VDZ: 68/84, 81%, vs anti-TNF: 20/34, 59%; p=0.002) and week 52 corticosteroid-free clinical remission (CFCR) rates (VDZ: 22/34, 65%, vs anti-TNF: 4/20, 20%; p=0.001). Conclusion: Compared with second-line anti TNF usage, the VDZ second-line cohort had significantly higher 52-week treatment persistence, UHUC survival, higher colectomy-free survival rates and higher week 52 CFCR. These data suggest that VDZ is an effective biologic in UC as a second-line therapy after anti-TNF exposure. It highlights the effect of biological order on clinically important outcomes.

Systematic review: the association between the gut microbiota and medical therapies in inflammatory bowel disease.

BACKGROUND: The gut microbiota has been implicated in the pathogenesis of inflammatory bowel disease (IBD), with Faecalibacterium prausnitizii associated with protection, and certain genera (including Shigella and Escherichia) associated with adverse features. The variability of patient response to medical therapies in IBD is incompletely understood. Given the recognised contribution of the microbiota to treatment efficacy in other conditions, there may be interplay between the gut microbiota, IBD medical therapy and IBD phenotype. AIMS: To evaluate the bidirectional relationship between IBD medical therapies and the gut microbiota. METHODS: We conducted a systematic search of MEDLINE and EMBASE. All original studies analysing interactions between the gut microbiota and established IBD medical therapies were included. RESULTS: We screened 1296 records; 19 studies were eligible. There was heterogeneity in terms of sample analysis, treatment protocols, and outcome reporting. Increased baseline α-diversity was observed in responders versus non-responders treated with exclusive enteral nutrition (EEN), infliximab, ustekinumab or vedolizumab. Higher baseline Faecalibacterium predicted response to infliximab and ustekinumab. A post-treatment increase in Faecalibacterium prausnitzii was noted in responders to aminosalicylates, anti-TNF medications and ustekinumab; conversely, this species decreased in responders to EEN. Escherichia was a consistent marker of unfavourable drug response, and its presence in the gut mucosa correlated with inflammation in aminosalicylate-treated patients. CONCLUSIONS: Both gut microbiota diversity and specific taxonomic features (including high abundance of Faecalibacterium) are associated with the efficacy of a range of IBD therapies. These findings hold promise for a potential role for the gut microbiota in explaining the heterogeneity of patient response to IBD treatments.

Beyond weight loss: evaluating the multiple benefits of bariatric surgery after Roux-en-Y gastric bypass and adjustable gastric band.

BACKGROUND: Despite the evidence for benefits beyond weight loss following bariatric surgery, assessments of surgical outcomes are often limited to changes in weight and remission of type 2 diabetes mellitus. To address this shortfall in assessment, the King's Obesity Staging System was developed. This system evaluates the individual in severity stages of physical, psychological, socio-economic and functional disease. These are categorised into disease domains arranged so as to allow an alphabetic mnemonic as Airways, Body Mass Index (BMI), Cardiovascular, Diabetes, Economic, Functional, Gonadal, Health Status (perceived) and (body) Image. METHODS: In this cohort study, patients were assessed before and 12 months after surgery using the modified King's Obesity Staging Score. We studied 217 consecutive patients undergoing Roux-en-Y gastric bypass (RYGB; N = 148) and laparoscopic adjustable gastric band (LAGB; N = 69) using the modified King's Obesity Staging System to determine health benefits after bariatric surgery. RESULTS: Preoperatively, the groups had similar BMI, but the RYGB group had worse Airways, Cardiovascular, and Diabetes scores (p < 0.05). After surgery, RYGB and LAGB produced improvements in all scores. In a subgroup paired analysis matched for preoperative Airways, BMI, Cardiovascular, and Diabetes scores, both procedures showed similar improvements in all scores, except for BMI where RYGB had a greater reduction than LAGB (p < 0.05). CONCLUSIONS: Both RYGB and LAGB deliver multiple benefits to patients as evaluated by the modified King's Obesity Staging System beyond BMI and glycaemic markers. A validated staging score such as the modified King's Obesity Staging System can be used to quantify these benefits.