Emergent ecological patterns and modelling of gut microbiomes in health and in disease.

Recent advancements in next-generation sequencing have revolutionized our understanding of the human microbiome. Despite this progress, challenges persist in comprehending the microbiome's influence on disease, hindered by technical complexities in species classification, abundance estimation, and data compositionality. At the same time, the existence of macroecological laws describing the variation and diversity in microbial communities irrespective of their environment has been recently proposed using 16s data and explained by a simple phenomenological model of population dynamics. We here investigate the relationship between dysbiosis, i.e. in unhealthy individuals there are deviations from the "regular" composition of the gut microbial community, and the existence of macro-ecological emergent law in microbial communities. We first quantitatively reconstruct these patterns at the species level using shotgun data, and addressing the consequences of sampling effects and statistical errors on ecological patterns. We then ask if such patterns can discriminate between healthy and unhealthy cohorts. Concomitantly, we evaluate the efficacy of different statistical generative models, which incorporate sampling and population dynamics, to describe such patterns and distinguish which are expected by chance, versus those that are potentially informative about disease states or other biological drivers. A critical aspect of our analysis is understanding the relationship between model parameters, which have clear ecological interpretations, and the state of the gut microbiome, thereby enabling the generation of synthetic compositional data that distinctively represent healthy and unhealthy individuals. Our approach, grounded in theoretical ecology and statistical physics, allows for a robust comparison of these models with empirical data, enhancing our understanding of the strengths and limitations of simple microbial models of population dynamics.

Characterization of Gut Microbiome Composition in Patients with Triple-Negative Breast Cancer Treated with Neoadjuvant Chemotherapy.

INTRODUCTION: Patients with triple-negative breast cancer (TNBC) achieving a pathological complete response (pCR) after neoadjuvant chemotherapy have a better event-free survival. The role of gut microbiome in early TNBC is underexplored. METHODS: Microbiome was analyzed by 16SrRNA sequencing. RESULTS: Twenty-five patients with TNBC treated with neoadjuvant anthracycline/taxane-based chemotherapy were included. Fifty-six percent achieved a pCR. Fecal samples were collected before (t0), at 1 (t1), and 8 weeks (t2) from chemotherapy. Overall, 68/75 samples (90.7%) were suitable for microbiome analysis. At t0, pCR group showed a significantly higher α-diversity as compared with no-pCR, (P = .049). The PERMANOVA test on ß-diversity highlighted a significant difference in terms of BMI (P = 0.039). Among patients with available matched samples at t0 and t1, no significant variation in microbiome composition was reported over time. CONCLUSIONS: Fecal microbiome analysis in early TNBC is feasible and deserves further investigation in order to unravel its complex correlation with immunity and cancer.

Immunolocalization of leptin and leptin receptor in colorectal mucosa of ulcerative colitis, Crohn's disease and control subjects with no inflammatory bowel disease.

The expression of leptin and leptin receptor (Ob-R) has been partially elucidated in colon of patients with inflammatory bowel diseases (IBDs), even though leptin is involved in angiogenesis and inflammation. We previously reported overexpression of GLUT5 fructose transporter, in aberrant clusters of lymphatic vessels in lamina propria of IBD and controls. Here, we examine leptin and Ob-R expression in the same biopsies. Specimens were obtained from patients with ulcerative colitis (UC), Crohn's disease (CD) and controls who underwent screening for colorectal cancer, follow-up after polypectomy or with a history of lower gastrointestinal symptoms. Immunohistochemistry revealed leptin in apical and basolateral membranes of short epithelial portions, Ob-R on the apical pole of epithelial cells. Leptin and Ob-R were also identified in structures and cells scattered in the lamina propria. In UC, a significant correlation between leptin and Ob-R in the lamina propria was found in all inflamed samples, beyond non-inflamed samples of the proximal tract, while in CD, it was found in inflamed distal samples. Most of the leptin and Ob-R positive areas in the lamina propria were also GLUT5 immunoreactive in inflamed and non-inflamed mucosa. A significant correlation of leptin or Ob-R expression with GLUT5 was observed in the inflamed distal samples from UC. Our findings suggest that there are different sites of leptin and Ob-R expression in large intestine and those in lamina propria do not reflect the status of mucosal inflammation. The co-localization of leptin and/or Ob-R with GLUT5 may indicate concomitance effects in colorectal lamina propria areas.

Microbiome One Health model for a healthy ecosystem.

The attention on microbiome research and its translation to application deployment is escalating along with diffused hype. There is real excitement in this new science, leveraging the growing potential of advances in molecular biology and sequencing techniques. Yet, despite the substantial efforts provided by the scientific communities, the true significance of research achievements requires coordinated and constructive actions across interdisciplinary fields. Individual researchers, universities, small and large companies, venture capitalists, and governments play a fundamental role in fostering collaboration and promoting knowledge that will benefit each other and sustain global prosperity. Making meaningful connections across different fields and getting a new perspective on how technological developments interrelate are the main drivers for creativity and progress. To help the broader innovation community focus on potentially new cross-sectorial developments, the One Health-microbiome-centric approach, defined here as "Microbiome One Health " , is considered as the efficient, holistic approach to product and service exploitations meant to preserve human well-being within a healthy ecosystem. The model opposes the biomedical system and generalizes the "One World-One Health ™" concept. The focus will be given to Nutrition as a driver of health and the food system for its commercial exploitation microbiome-centric, specifically at the interface of human/animal/agricultural. Remarkably, at the interface of humans/animals, the interaction with pets, specifically dogs, has been recognized as a driving force of novel microbiome exploitation.

Refractory Crohn's Disease: Perspectives, Unmet Needs and Innovations.

Crohn's disease (CD) is a complex, chronic inflammatory bowel disease characterized by unpredictable flare-ups and periods of remission. Despite advances in treatment, CD remains a significant health burden, leading to substantial direct healthcare costs and out-of-pocket expenses for patients, especially in the first-year post-diagnosis. The impact of CD on patients' quality of life is profound, with significant reductions in physical, emotional, and social well-being. Despite advancements in therapeutic options, including biologics, immunomodulators, and small molecules, many patients struggle to achieve or maintain remission, leading to a considerable therapeutic ceiling. This has led to an increased focus on novel and emerging treatments. This context underscores the importance of exploring advanced and innovative treatment options for managing refractory CD. By examining the latest approaches, including immunomodulators, combination therapies, stem cell therapies, and emerging treatments like fecal microbiota transplantation and dietary interventions, there is an opportunity to gain a comprehensive understanding of how best to address and manage refractory cases of CD.

Short-Chain Fatty Acids and Human Health: From Metabolic Pathways to Current Therapeutic Implications.

The gastrointestinal tract is home to trillions of diverse microorganisms collectively known as the gut microbiota, which play a pivotal role in breaking down undigested foods, such as dietary fibers. Through the fermentation of these food components, short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate are produced, offering numerous health benefits to the host. The production and absorption of these SCFAs occur through various mechanisms within the human intestine, contingent upon the types of dietary fibers reaching the gut and the specific microorganisms engaged in fermentation. Medical literature extensively documents the supplementation of SCFAs, particularly butyrate, in the treatment of gastrointestinal, metabolic, cardiovascular, and gut-brain-related disorders. This review seeks to provide an overview of the dynamics involved in the production and absorption of acetate, propionate, and butyrate within the human gut. Additionally, it will focus on the pivotal roles these SCFAs play in promoting gastrointestinal and metabolic health, as well as their current therapeutic implications.

Emergent Functional Organization of Gut Microbiomes in Health and Diseases.

Continuous and significant progress in sequencing technologies and bioinformatics pipelines has revolutionized our comprehension of microbial communities, especially for human microbiomes. However, most studies have focused on studying the taxonomic composition of the microbiomes and we are still not able to characterize dysbiosis and unveil the underlying ecological consequences. This study explores the emergent organization of functional abundances and correlations of gut microbiomes in health and disease. Leveraging metagenomic sequences, taxonomic and functional tables are constructed, enabling comparative analysis. First, we show that emergent taxonomic and functional patterns are not useful to characterize dysbiosis. Then, through differential abundance analyses applied to functions, we reveal distinct functional compositions in healthy versus unhealthy microbiomes. In addition, we inquire into the functional correlation structure, revealing significant differences between the healthy and unhealthy groups, which may significantly contribute to understanding dysbiosis. Our study demonstrates that scrutinizing the functional organization in the microbiome provides novel insights into the underlying state of the microbiome. The shared data structure underlying the functional and taxonomic compositions allows for a comprehensive macroecological examination. Our findings not only shed light on dysbiosis, but also underscore the importance of studying functional interrelationships for a nuanced understanding of the dynamics of the microbial community. This research proposes a novel approach, bridging the gap between microbial ecology and functional analyses, promising a deeper understanding of the intricate world of the gut microbiota and its implications for human health.

Characterization of multifunctional nanosystems based on the avidin-nucleic acid interaction as signal enhancers in immuno-detection.

The Avidin-Nucleic-Acids-Nano-Assembly (ANANAS) is a kind of soft poly avidin nanoparticle originating from the high affinity interaction between avidin and the nucleic acids. In this work we investigated the possibility of transforming ANANAS cores into stoichiometrically controlled multifunctional nanoparticles through a "one-pot" procedure, and we measured in a quantitative way their ability to work as reagents for enhanced immunodiagnostic detection. Initially, we measured the ANANAS loading capability for biotinylated proteins of different nature. About 200 molecules of biotin-horseradish-peroxidase (40KDa b-HRP) and 60 molecules of biotin-immunoglobulin-G (150KDa b-IgG) could be accommodated onto each nanoparticle, showing that steric limitations dictate the number of loadable entities. Stoichiometrically controlled functional assemblies were generated by mixing core particles with subsaturating amounts of b-HRP and b-IgG. When applied as detection reagents in an Enzyme-Linked-ImmunoSorbed-Assay (ELISA), these assemblies were up to two-orders of magnitude more sensitive than commercial HRP-based reagents. Assemblies of different composition displayed different efficacy, indicating that the system functionality can be fine-tuned. Within-assay variability (CV%), measured to assess if the assembly procedure is reproducible, was within 10%. Stability experiments demonstrated that the functionalyzed assemblies are stable in solution for more than one week. In principle, any biotinylated function can be loaded onto the core particle, whose high loading capacity and tunability may open the way toward further application in biomedicine.

Machine Learning and Canine Chronic Enteropathies: A New Approach to Investigate FMT Effects.

Fecal microbiota transplantation (FMT) represents a very promising approach to decreasing disease activity in canine chronic enteropathies (CE). However, the relationship between remission mechanisms and microbiome changes has not been elucidated yet. The main objective of this study was to report the clinical effects of oral freeze-dried FMT in CE dogs, comparing the fecal microbiomes of three groups: pre-FMT CE-affected dogs, post-FMT dogs, and healthy dogs. Diversity analysis, differential abundance analysis, and machine learning algorithms were applied to investigate the differences in microbiome composition between healthy and pre-FMT samples, while Canine Chronic Enteropathy Clinical Activity Index (CCECAI) changes and microbial diversity metrics were used to evaluate FMT effects. In the healthy/pre-FMT comparison, significant differences were noted in alpha and beta diversity and a list of differentially abundant taxa was identified, while machine learning algorithms predicted sample categories with 0.97 (random forest) and 0.87 (sPLS-DA) accuracy. Clinical signs of improvement were observed in 74% (20/27) of CE-affected dogs, together with a statistically significant decrease in CCECAI (median value from 5 to 2 median). Alpha and beta diversity variations between pre- and post-FMT were observed for each receiver, with a high heterogeneity in the response. This highlighted the necessity for further research on a larger dataset that could identify different healing patterns of microbiome changes.

A specific microbiota signature is associated to various degrees of ulcerative colitis as assessed by a machine learning approach.

Ulcerative colitis (UC) is a complex immune-mediated disease in which the gut microbiota plays a central role, and may determine prognosis and disease progression. We aimed to assess whether a specific microbiota profile, as measured by a machine learning approach, can be associated with disease severity in patients with UC. In this prospective pilot study, consecutive patients with active or inactive UC and healthy controls (HCs) were enrolled. Stool samples were collected for fecal microbiota assessment analysis by 16S rRNA gene sequencing approach. A machine learning approach was used to predict the groups' separation. Thirty-six HCs and forty-six patients with UC (20 active and 26 inactive) were enrolled. Alpha diversity was significantly different between the three groups (Shannon index: p-values: active UC vs HCs = 0.0005; active UC vs inactive UC = 0.0273; HCs vs inactive UC = 0.0260). In particular, patients with active UC showed the lowest values, followed by patients with inactive UC, and HCs. At species level, we found high levels of Bifidobacterium adolescentis and Haemophilus parainfluenzae in inactive UC and active UC, respectively. A specific microbiota profile was found for each group and was confirmed with sparse partial least squares discriminant analysis, a machine learning-supervised approach. The latter allowed us to observe a perfect class prediction and group separation using the complete information (full Operational Taxonomic Unit table), with a minimal loss in performance when using only 5% of features. A machine learning approach to 16S rRNA data identifies a bacterial signature characterizing different degrees of disease activity in UC. Follow-up studies will clarify whether such microbiota profiling are useful for diagnosis and management.

Salivary microbiota composition may discriminate between patients with eosinophilic oesophagitis (EoE) and non-EoE subjects.

BACKGROUND: Data on the role of the microbiome in adult patients with eosinophilic oesophagitis (EoE) are limited. AIMS: To prospectively collect and characterise the salivary, oesophageal and gastric microbiome in patients with EoE, further correlating the findings with disease activity. METHODS: Adult patients with symptoms of oesophageal dysfunction undergoing upper endoscopy were consecutively enrolled. Patients were classified as EoE patients, in case of more than 15 eosinophils per high-power field, or non-EoE controls, in case of lack of eosinophilic infiltration. Before and during endoscopy, saliva, oesophageal and gastric fundus biopsies were collected. Microbiota assessment was performed by 16 s rRNA analysis. A Sparse Partial Least Squares Discriminant Analysis (sPLS-DA) was implemented to identify biomarkers. RESULTS: Saliva samples were collected from 29 EoE patients and 20 non-EoE controls;, biopsies from 25 EoE and 5 non-EoE controls. In saliva samples, 23 Amplicon Sequence Variants (ASVs) were positively associated with EoE and 27 ASVs with controls, making it possible to discriminate between EoE and non-EoE patients with a classification error (CE) of 24%. In a validation cohort, the accuracy, sensitivity, specificity, positive predictive value and negative predictive value of this model were 78.6%, 80%, 75%, 80% and 60%, respectively. Moreover, the analysis of oesophageal microbiota samples observed a clear microbial pattern able to discriminate between active and inactive EoE (CE = 8%). CONCLUSION: Our preliminary data suggest that salivary metabarcoding analysis in combination with machine learning approaches could become a valid, cheap, non-invasive test to segregate between EoE and non-EoE patients.

Serum oncostatin M predicts mucosal healing in patients with inflammatory bowel diseases treated with anti-TNF, but not vedolizumab.

BACKGROUND: Oncostatin M was recently highlighted as a promising biomarker for therapeutic effectiveness in inflammatory bowel diseases (IBD), with particular regard for infliximab. The primary aim was to evaluate the ability of serum oncostatin M to predict endoscopic response to different drugs in IBD. METHODS: We selected two different cohorts of patients with IBD, treated with anti-TNF (infliximab and adalimumab) or with vedolizumab. Therapeutic response was evaluated at week 54 in terms of mucosal healing. Serum oncostatin M and C-reactive protein were measured at baseline; fecal calprotectin was measured at baseline and after 14 weeks of treatment. We evaluated the association of these biomarkers with mucosal healing at week 54. RESULTS: Among 66 patients treated with anti-TNFs and 68 treated with vedolizumab, 35 and 31 attained mucosal healing, respectively. Mucosal healing at 54 weeks was significantly associated with low oncostatin M levels at baseline in the anti-TNF cohort; the diagnostic accuracy of oncostatin M at baseline in predicting mucosal healing was 0.91 (95% CI 0.84 to 0.99) in the anti-TNF cohort and 0.56 (95% CI 0.43 to 0.70, P < 0.001) in the vedolizumab cohort. Mucosal healing was also associated with low fecal calprotectin levels at week 14 in both cohorts. CONCLUSION: Our study suggests that serum oncostatin M is a drug-specific biomarker, since it could be used to predict therapeutic effectiveness to anti-TNFs but not to vedolizumab. Moreover, these results emphasize the utility of serum oncostatin M measurement in patients treated with anti-TNF.

Faecal Microbiome Transplantation as a Solution to Chronic Enteropathies in Dogs: A Case Study of Beneficial Microbial Evolution.

Chronic enteropathies (CE) are gastrointestinal diseases that afflict about one in five dogs in Europe. Conventional therapeutic approaches include dietary intervention, pharmacological treatment and probiotic supplements. The patient response can be highly variable and the interventions are often not resolutive. Moreover, the therapeutic strategy is usually planned (and gradually corrected) based on the patient's response to empirical treatment, with few indirect gut health indicators useful to drive clinicians' decisions. The ever-diminishing cost of high-throughput sequencing (HTS) allows clinicians to directly follow and characterise the evolution of the whole gut microbial community in order to highlight possible weaknesses. In this framework, faecal microbiome transplantation (FMT) is emerging as a feasible solution to CE, based on the implant of a balanced, eubiotic microbial community from a healthy donor to a dysbiotic patient. In this study, we report the promising results of FMT carried out in a 9-year-old dog suffering from CE for the last 3 years. The patient underwent a two-cycle oral treatment of FMT and the microbiota evolution was monitored by 16S rRNA gene sequencing both prior to FMT and after the two administrations. We evaluated the variation of microbial composition by calculating three different alpha diversity indices and compared the patient and donor data to a healthy control population of 94 dogs. After FMT, the patient's microbiome and clinical parameters gradually shifted to values similar to those observed in healthy dogs. Symptoms disappeared during a follow-up period of six months after the second FMT. We believe that this study opens the door for potential applications of FMT in clinical veterinary practice and highlights the need to improve our knowledge on this relevant topic.

Switching from Infliximab Originator to SB2 Biosimilar in Inflammatory Bowel Diseases: A Multicentric Prospective Real-Life Study.

BACKGROUND: Current literature still lacks studies evaluating the effectiveness and safety of switching from Infliximab originator to SB2 biosimilar in Inflammatory Bowel Diseases (IBDs). We aimed to verify the ability of SB2 to maintain the clinical and biochemical response induced by originator after switching. As secondary outcome, we aimed to verify safety, tolerability and immunogenicity of SB2 biosimilar compared with its IFX originator. METHODS: We prospectively enrolled all patients who switched from originator to SB2 at three Italian IBD Units from August 2018 to April 2020. We collected clinical and biochemical data at the time of switch (T0), and at the first (T1) and the second (T2) visits after switching (mean time from switching: 135 and 329 days, respectively). In addition, data regarding therapeutic drug monitoring at T0 and T1 were recorded. RESULTS: Eighty-five IBD patients (28 with Ulcerative Colitis and 57 with Crohn's Disease) were included in the study. At T1, we observed statistically significant modifications in clinical activity of disease (70 patients were in clinical remission at baseline and 60 at T1 p = 0.02), but not at T2 (p = 0.3). Fecal calprotectin values were not different both at T1 and T2 (both p = 0.9) as well as the rate of concomitant treatment with steroids (p = 0.2 and p = 0.1) or immunosuppressants (p = 0.1 and p = 1.0). Moreover, the need for therapeutic optimization from T0 to T1 and from T1 to T2 was found significant (both p = 0.01). No anti-drug antibodies were identified at T1, and no serious adverse events were recorded. CONCLUSIONS: Overall, our data show that most of the patients switching from Infliximab originator to SB2 maintain the clinical and biochemical remission for at least 1 year. Further data are necessary to understand the clinical implications of these findings in the long term.

Rapid point-of-care anti-infliximab antibodies detection in clinical practice: comparison with ELISA and potential for improving therapeutic drug monitoring in IBD patients.

Anti-drug antibodies can interfere with the activity of anti-tumor necrosis factor (TNF) agents by increasing drug clearance via direct neutralization. The presence of anti-drug antibodies is clinically relevant when trough drug concentrations are undetectable or sub-therapeutic. However, traditional immunoassay is not easily and rapidly accessible, making the translation of the results into treatment adjustment difficult. The availability of a point-of-care (POC) test for therapeutic drug monitoring (TDM) might represent an important step forward for improving the management of inflammatory bowel disease (IBD) patients in clinical practice. In this pilot study, we compared the results obtained with POC tests with those obtained by enzyme-linked immunosorbent assay (ELISA) in a group of IBD patients treated with Infliximab (IFX). We showed that POC test can reliably detect presence of antibody-to-IFX with 100% of specificity and 76% sensitivity, in strong agreement with the ELISA test (k-coefficient = 0.84).

Factors associated with disability in patients with ulcerative colitis: A cross-sectional study.

OBJECTIVES: Ulcerative colitis (UC) can give rise to several restrictions of patients' working and social activities. We aimed to determine the association between disease chronicity and the state of disability in a large population with UC. METHODS: We recruited consecutive patients with UC attending the inflammatory bowel disease (IBD) unit of the Azienda Ospedaliera of Padua between July and December 2017. We collected patients' characteristics and clinical information, and all participants completed the IBD questionnaire (IBDQ) for quality of life assessment and the IBD disability index (IBD-DI) questionnaire. Using univariate logistic regression models we assessed whether the patients' characteristics and IBD-related variables were associated with an IBD-DI score ≤3.5. Statistically significant variables in the univariate analyses were then included in a multivariate regression model. Correlations between IBD-DI and all the above mentioned characteristics were investigated using the Spearman's rank correlation coefficient. RESULTS: We included 201 patients. A positive correlation was observed between IBD-DI and IBDQ (r = 0.82, P < 0.001). Multivariate regression modelling identified the following as independent factors related to disability: active disease (partial Mayo score ≥2) (odds ratio [OR] 6.54, 95% CI 3.21-13.22), the presence of extraintestinal manifestations (EIM) (OR 2.48, 95%, CI 1.11-5.54) and occasional alcohol consumption (OR 0.39, 95% CI 0.20-0.76). CONCLUSIONS: Impaired disability is mainly correlated with disease activity, the presence of EIM and no alcohol consumption. Moreover, there is a strong correlation with patients' quality of life. Therefore, in clinical practice, greater awareness of IBD-related disability is needed to better manage patients' outcomes.

Matrix Metalloproteinase 3 Predicts Therapeutic Response in Inflammatory Bowel Disease Patients Treated With Infliximab.

BACKGROUND AND AIMS: Inflammatory bowel diseases (IBDs) are treated with anti-TNF agents. Strategies to monitor response to therapy may improve clinical control of the disease and reduce economical costs. Previous evidence suggests cleavage of infliximab (IFX) by Matrix Metalloproteinase 3 (MMP3) as a mechanism leading to loss of response. Our study aimed to evaluate if MMP3 serum levels could be considered an early marker of anti-TNF nonresponse and to analyze the correlation with other biochemical markers of treatment failure such as IFX trough levels and anti-IFX antibodies, inflammatory markers, and albumin levels. METHODS: Retrospectively, 73 IBD patients who had received IFX for at least 1 year were enrolled: 35 patients were responders and 38 were nonresponders at 52 weeks. Clinical and biochemical data (Harvey-Bradshaw index [HBI], Mayo score, body mass index [BMI], C-reactive protein [CRP], fecal calprotectin and albumin levels), MMP3 serum levels, and drug monitoring were assessed at baseline, postinduction, and 52 weeks. RESULTS: The MMP3 levels were similar at baseline (19.83 vs 17.92 ng/mL), but at postinduction, patients who failed to respond at 1 year had significantly higher levels than patients who responded (26.09 vs 8.68 ng/mL, P < 0.001); the difference was confirmed at week 52 (29.56 vs 11.48 ng/mL, P < 0.001). The MMP3 levels tended to be higher in patients without antidrug antibodies than in patients with antidrug antibodies at postinduction and 52 weeks. CONCLUSIONS: The MMP3 serum determination may represent an early marker of response to infliximab.

Faecal microbiota transplantation in Clostridioides difficile infection: real-life experience from an academic Italian hospital.

BACKGROUND: Faecal microbiota transplantation (FMT) is a reasonable therapeutic option for the treatment of Clostridioides difficile infection (CDI) recurrent and refractory (RCDI) to therapy, but little evidence on the long-term impact of this therapy is currently available in the literature. The aim of this study was to evaluate the efficacy and safety of FMT in recurrent and refractory CDI and the modifications of the recipient's gut microbiota in the medium-long term. METHODS: This prospective study collects the clinical and laboratory data of RCDI patients treated with FMT by colonoscopy from February 2016 to October 2019. Stool samples for metagenomic analysis were collected pre-FMT at 1 week and at 6 and 12-24 months post-FMT. RESULTS: In the study period, 20 FMT procedures were performed on 19 patients. Overall, FMT was effective in 85% of treated patients. No serious adverse event was recorded. In the medium- to long-term follow up, a newly diagnosed case of collagenous colitis was observed. Post-FMT, significant changes in microbiota were observed, characterised by the transition from a low- to a greater-diversity profile. Therefore, FMT restores eubiosis and maintains it over time. CONCLUSION: FMT is a safe and effective treatment option in RCDI patients. This procedure induces profound microbiota changes that explain its high clinical efficacy.

Microbiota changes induced by microencapsulated sodium butyrate in patients with inflammatory bowel disease.

BACKGROUND: Butyrate has shown anti-inflammatory and regenerative properties, providing symptomatic relief when orally supplemented in patients suffering from various colonic diseases. We investigated the effect of a colonic-delivery formulation of butyrate on the fecal microbiota of patients with inflammatory bowel diseases (IBDs). METHODS: In this double-blind, placebo-controlled, pilot study, 49 IBD patients (n = 19 Crohn's disease, CD and n = 30 ulcerative colitis, UC) were randomized to oral administration of microencapsulated-sodium-butyrate (BLM) or placebo for 2 months, in addition to conventional therapy. Eighteen healthy volunteers (HVs) were recruited to provide a healthy microbiota model of the local people. Fecal microbiota from stool samples was assessed by 16S sequencing. Clinical disease activity and quality of life (QoL) were evaluated before and after treatment. KEY RESULTS: At baseline, HVs showed a different microbiota composition compared with IBD patients. Sodium-butyrate altered the gut microbiota of IBD patients by increasing bacteria able to produce SCFA in UC patients (Lachnospiraceae spp.) and the butyrogenic colonic bacteria in CD patients (Butyricicoccus). In UC patients, QoL was positively affected by treatment. CONCLUSIONS AND INFERENCES: Sodium-butyrate supplementation increases the growth of bacteria able to produce SCFA with potentially anti-inflammatory action. The clinical impact of this finding requires further investigation.