Machine learning and artificial intelligence in the multi-omics approach to gut microbiota

The gut microbiome is involved in human health and disease, and its comprehensive understanding is necessary to exploit it as a diagnostic or therapeutic tool. Multi-omics approaches, including metagenomics, metatranscriptomics, metabolomics, and metaproteomics, enable depicting the complexity of the gut microbial ecosystem. However, these tools generate a large data stream, which integration is needed to produce clinically useful readouts but, in turn, might be difficult to carry out with conventional statistical methods.

Leggi
Marzo 2025

Microbiota-directed intervention in living donor liver transplant recipients: protocol for a randomised double-blind placebo-controlled trial

Introduction
Acute-on-chronic liver failure (ACLF) patients have the highest propensity for post-liver transplantation (LT) infections and mortality. Liver-associated diseases have been one of the primary targets for synbiotic therapy to augment immunity and mitigate infections. However, despite multiple studies showing benefits of synbiotics in liver diseases, data on their use following LT are sparse.

Methods and analysis
This randomised placebo-controlled study aims to assess the impact of synbiotics in ACLF patients undergoing living donor liver transplantation (LDLT). Following randomisation by computer-generated block number sequence, 3 days prior to LDLT, the intervention arm will receive standard medical treatment and synbiotics (VSL#3 a probiotic, and Yogut, prebiotic and probiotic combination) for 6 weeks, while the control arm will receive standard medical treatment with a placebo. The patients will be followed up for 6 months to study the clinical and biochemical outcomes. The primary objective is to compare the difference in the occurrence of infectious complications between the patients who receive synbiotics versus placebo during the 6-month period following LDLT. The secondary objectives include assessing the qualitative and quantitative change in microbiota with synbiotics and LDLT, adverse reactions due to synbiotics, and post-LT morbidity and mortality. The minimum sample size comes to 71 in each group. The first 50 patients in the study protocol will undergo gut microbiome analysis using 16s metagenomic and nanopore sequencing to analyse the microbial composition before starting synbiotics/placebo and at 6 weeks after LDLT.

Ethics and dissemination
The study is approved by the Research Ethics Committee of Amrita Institute of Medical Sciences, Kochi, India (IEC-AIMS-2022-GISUR-203) and registered in the Clinical Trial Registry of India (CTRI) CTRI/2022/10/046327. The results of the trial will be disseminated by presentation at national/international conferences and publication in peer-reviewed journals.

Trial registration number
CTRI/2022/10/046327 – Clinical Trial Registry of India

Leggi
Marzo 2025

Is the biogeography of the mucosa-associated microbiota a key factor affecting primary sclerosing cholangitis disease course and treatment?

We have read with interest the contribution by Bedke et al,1 reporting changes in the stool microbiota associated with primary sclerosing cholangitis (PSC) in human and murine models of the disease. These changes coincide with an expansion of FoxP3+T reg cells, a response also linked with luminal butyrate concentrations and/or other goods and services arising from select commensal bacteria.2 Furthermore, the authors find patients with PSC with an associated IBD (PSC-IBD) as well as mice receiving faecal transfer from such patients experience a milder form of IBD, or attenuation of colitis, respectively. Their findings expand on those from Awoniyi et al, linking bile acid ecology and select stool bacteria deemed protective or pathogenic in a murine model of PSC, as well as an association of these microbial signatures with disease severity in patients with PSC.3 Attribution of the beneficial effects to the luminal/stool…

Leggi
Marzo 2025

Exploring the role of genetics, gut microbiota and blood metabolites in IBD

We have read with interest the article by Bonfils et al, which explores the impact of parental IBD on offspring risk using a large Danish cohort.1 Their findings underscore the significance of genetic predisposition and shared environmental factors, with maternal IBD diagnosis before childbirth showing the highest risk (adjusted HR 6.27) and a similar pattern observed with paternal IBD (adjusted HR 5.26). Despite the clear inheritance pattern indicated by Bonfils et al, previous genome-wide association studies (GWAS) have shown that genetic predisposition accounts for only a small portion of IBD risk, ranging from 8.2% to 13.1%.2 This suggests that a substantial portion of IBD risk remains unexplained by genetics alone. Traditional GWAS approaches typically focus on direct associations between single nucleotide polymorphisms (SNPs) and disease phenotypes, overlooking complex biological interactions among genes, gut microbiota and blood metabolites that shape IBD.3 Furthermore, the extent…

Leggi
Marzo 2025

Faecal microbiota transplantation combined with platinum-based doublet chemotherapy and tislelizumab as first-line treatment for driver-gene negative advanced non-small cell lung cancer (NSCLC): study protocol for a prospective, multicentre, single-arm exploratory trial

Introduction
The standard first-line treatment for driver-gene negative advanced non-small cell lung cancer (NSCLC) is chemotherapy combined with immunotherapy. However, owing to the immune microenvironment imbalance and immune status impairment caused by repeated chemotherapy, as well as the primary or secondary resistance to immune checkpoint inhibitors, the efficacy of immunotherapy combined with chemotherapy remains unsatisfactory. Recent studies have shown that faecal microbiota transplantation (FMT) can modulate the intestinal microflora, influence the tumour immune microenvironment and even enhance the efficacy of immunotherapy. Hence, we conduct such a prospective, exploratory study to evaluate the efficacy and safety of integrating FMT with standard first-line treatment in patients with driver-gene negative advanced NSCLC.

Methods and analysis
FMT-JSNO-02 (NCT06403111) is a prospective, multicentre, single-arm exploratory study. It is planned to include 62 cases of previously untreated driver-gene negative, Eastern Cooperative Oncology Group Performance Status 0–1, programmed death ligand 1

Leggi
Marzo 2025

NapBiome trial: Targeting gut microbiota to improve sleep rhythm and developmental and behavioural outcomes in early childhood in a birth cohort in Switzerland – a study protocol

Introduction
The gut–brain axis plays a crucial role in the regulation and development of psychological and physical processes. The first year of life is a critical period for the development of the gut microbiome, which parallels important milestones in establishing sleep rhythm and brain development. Growing evidence suggests that the gut microbiome influences sleep, cognition and early neurodevelopment. For term-born and preterm-born infants, difficulties in sleep regulation may have consequences on health. Identifying effective interventions on the gut–brain axis in early life is likely to have long-term implications for the health and development of at-risk infants.

Methods and analyses
In this multicentre, four-group, double-blinded, placebo (PLC)-controlled randomised trial with a factorial design, 120 preterm-born and 260 term-born infants will be included. The study will investigate whether the administration of daily synbiotics or PLC for a duration of 3 months improves sleep patterns and neurodevelopmental outcomes up to 2 years of age. The trial will also: (1) determine the association between gut microbiota, sleep patterns and health outcomes in children up to 2 years of age; and (2) leverage the interactions between gut microbiota, brain and sleep to develop new intervention strategies for at-risk infants.

Ethics and dissemination
The NapBiome trial has received ethical approval by the Committee of Northwestern and Central Switzerland and Canton Vaud, Switzerland (#2024–01681). Outcomes will be disseminated through publication and will be presented at scientific conferences. Metagenomic data will be shared through the European Nucleotide Archive.

Trial registration number
The US National Institutes of Health NCT06396689.

Leggi
Marzo 2025