Mendelian randomisation analysis reveals the possible causal relationship between infections, microbiota and clinical disease

We read with interest the recent report by Nashed et al that described changes in the microbiota caused by viral infections, which in turn affected the severity of the clinical disease.1–4 Interactions between viral infections and microbiota complicate their relationship with host immunity and clinical diseases. However, it is unclear whether those associations are causal. Furthermore, the interactions between the microbiota and infections, as well as the outcomes of those interactions, have only been studied to a limited extent.5–8 We conducted an in-depth statistical analysis based on two-sample bidirectional Mendelian randomisation (MR) to broaden our understanding and provide a comprehensive assessment of the causal relationship between 9 common infections, 140 microbes and 38 clinical diseases. As instrumental variables for MR analysis, independent genetic variants with genome-wide suggestive significance (p

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Giugno 2024

Proton pump inhibitors alter gut microbiota by promoting oral microbiota translocation: a prospective interventional study

Background
The mechanism by which proton pump inhibitors (PPIs) alter gut microbiota remains to be elucidated. We aimed to learn whether PPI induced gut microbiota alterations by promoting oral microbial translocation.

Methods
Healthy adult volunteers were randomly assigned: PP group (n=8, 40 mg esomeprazole daily for seven days) and PM group (n=8, 40 mg esomeprazole along with chlorhexidine mouthwash after each meal for seven days). Fecal and saliva samples were analysed using 16S ribosomal RNA sequencing. Mouse models were introduced to confirm the findings in vivo, while the effect of pH on oral bacteria proliferation activity was investigated in vitro.

Results
Taxon-based analysis indicated that PPI administration increased Streptococcus abundance in gut microbiota (P

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Giugno 2024

The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines

The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.

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Giugno 2024

Revisiting the donor screening protocol of faecal microbiota transplantation (FMT): a systematic review

We read with interest the recent work by Haifer et al,1 which highlighted the importance of donor selection in determining the clinical efficacy of treating ulcerative colitis (UC) using faecal microbiota transplantation (FMT), with one donor having 100% efficacy compared with a second donor (36% efficacy). Considering the impact of COVID-19 pandemic on FMT, updated guidance including patient selection, donor recruitment and selection, FMT procedures and stool manufacturing was provided by worldwide FMT experts in international guideline by Ianiro et al.2 The US Food and Drug Administration (FDA) has recommended that FMT donor screening must include a questionnaire specifically addressing risk factors for colonisation with multidrug-resistant organisms (MDROs) and stool testing for MDROs, including extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, vancomycin-resistant enterococci (VRE), carbapenem-resistant Enterobacteriaceae (CRE) and methicillin-resistant Staphylococcus aureus (MRSA) at minimum.3 The evolution of FMT and the introduction of essential donor screening requirements…

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Maggio 2024

Basal levels of microbiota-driven subclinical inflammation are associated with anastomotic leak in patients with colorectal cancer

In our recent publication in Gut,1 we showed that preoperative gut microbiota was causally linked to the development of anastomotic leak (AL) after colorectal cancer (CRC) surgery. AL results from impaired healing of the colonic wound and leads to the leakage of intestinal content into the abdomen. Using faecal microbiota transplantation (FMT) in mice with faecal samples from 18 patients with CRC, we established that preanastomosis expression of mucosal proinflammatory cytokines, namely macrophage inflammatory protein-1 alpha (MIP-1α), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein 2 (MIP-2) and interleukin-17A/F (IL-17A/F), was increased in patients who later developed AL. Most importantly, these higher basal cytokine levels were driven by gut microbiota, as FMT from these patients led to higher cytokine levels in mice. To corroborate these findings, we now expanded the analysis to our cohort of 77 patients with CRC who underwent a bowel resection with anastomosis (

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Maggio 2024

Dietary fibre (and animal products) modulate the association between tryptophan intake, gut microbiota and type 2 diabetes: but how?

There is an increased interest in the interplay among diet, gut microbiota and health. Studies have often investigated the influence of diets, foods and dietary components on gut microbiota or whether microbiota can modify the effect of dietary interventions and the role of such modifications on health outcomes.1 This has been fueled by promising results emerging from large landmark studies pinpointing the role of gut microbiota as an important determinant for metabolic responses and from an improved understanding of how gut microbiota affect metabolism and how it mediate effects through generation of metabolites.1–3 The faecal metabolome has shown to explain up to 60% variability in gut microbial composition, some of them are key mediators of physiological effects directly produced or modified by gut microbiota such as bile acids, short-chain fatty acids, lipopolysaccharides and trimethylamine N-oxide.3 The concentrations of these…

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Maggio 2024