Risultati per: Microbiota e steatosi epatica: quali evidenze?

Introduction
Gut microbiota (GM) appears critical for gastrointestinal symptoms, but whether alterations in GM are associated with increased risk of postoperative gastrointestinal dysfunction (POGID) in older patients with colon cancer (CC) undergoing elective colon resection remains unclear.

Methods and analysis
This study aims to prospectively recruit 284 elderly patients with CC undergoing elective colon resection. GM of fresh faeces specimens is characterised using 16S rRNA gene sequencing. Data are collected preoperatively, daily postoperatively during the in-hospital stay, and follow-up visits are scheduled four times within 30 days after discharge. Associations with POGID will be investigated using logistic regression models to calculate ORs with 95% CIs. The models include the adjustment for age, sex, frequency of spicy diet, coffee drinking and tea drinking, tobacco and alcohol history, diabetes, obesity, gastroenteritis, preoperative gut microbial composition. Furthermore, we will use joint modelling for longitudinal data to study several outcome variables simultaneously.

Ethics and dissemination
This study was approved by the Institutional Review Board of West China Hospital, Sichuan University (IRB Number: 20201334). The results will be disseminated through peer-reviewed publications or conference presentations.

Trial registration number
It has been registered in PROSPERO, number CRD42019145032. It has been registered in the Chinese clinical trial registry, number ChiCTR2100043646.

Objective
Using faecal shotgun metagenomic sequencing, we identified the depletion of Lactobacillus gallinarum in patients with colorectal cancer (CRC). We aimed to determine the potential antitumourigenic role of L. gallinarum in colorectal tumourigenesis.

Design
The tumor-suppressive effect of L. gallinarum was assessed in murine models of CRC. CRC cell lines and organoids derived from patients with CRC were cultured with L. gallinarum or Escherichia coli MG1655 culture-supernatant to evaluate cell proliferation, apoptosis and cell cycle distribution. Gut microbiota was assessed by 16S ribosomal DNA sequencing. Antitumour molecule produced from L. gallinarum was identified by liquid chromatography mass spectrometry (LC-MS/MS) and targeted mass spectrometry.

Results
L. gallinarum significantly reduced intestinal tumour number and size compared with E. coli MG1655 and phosphate-buffered saline in both male and female murine intestinal tumourigenesis models. Faecal microbial profiling revealed enrichment of probiotics and depletion of pathogenic bacteria in L. gallinarum-treated mice. Culturing CRC cells with L. gallinarum culture-supernatant (5%, 10% and 20%) concentration-dependently suppressed cell proliferation and colony formation. L. gallinarum culture-supernatant significantly promoted apoptosis in CRC cells and patient-derived CRC organoids, but not in normal colon epithelial cells. Only L. gallinarum culture-supernatant with fraction size

This multicenter cohort study analyzes the associations between intratumoral microbiota and prognostication in patients with nasopharyngeal carcinoma.

Objective
Reducing FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) can be clinically beneficial in IBS but the mechanism is incompletely understood. We aimed to detect microbial signatures that might predict response to the low FODMAP diet and assess whether microbiota compositional and functional shifts could provide insights into its mode of action.

Design
We used metagenomics to determine high-resolution taxonomic and functional profiles of the stool microbiota from IBS cases and household controls (n=56 pairs) on their usual diet. Clinical response and microbiota changes were studied in 41 pairs after 4 weeks on a low FODMAP diet.

Results
Unsupervised analysis of baseline IBS cases pre-diet identified two distinct microbiota profiles, which we refer to as IBSP (pathogenic-like) and IBSH (health-like) subtypes. IBSP microbiomes were enriched in Firmicutes and genes for amino acid and carbohydrate metabolism, but depleted in Bacteroidetes species. IBSH microbiomes were similar to controls. On the low FODMAP diet, IBSH and control microbiota were unaffected, but the IBSP signature shifted towards a health-associated microbiome with an increase in Bacteroidetes (p=0.009), a decrease in Firmicutes species (p=0.004) and normalisation of primary metabolic genes. The clinical response to the low FODMAP diet was greater in IBSP subjects compared with IBSH (p=0.02).

Conclusion
50% of IBS cases manifested a ‘pathogenic’ gut microbial signature. This shifted towards the healthy profile on the low FODMAP diet; and IBSP cases showed an enhanced clinical responsiveness to the dietary therapy. The effectiveness of FODMAP reduction in IBSP may result from the alterations in gut microbiota and metabolites produced. Microbiota signatures could be useful as biomarkers to guide IBS treatment; and investigating IBSP species and metabolic pathways might yield insights regarding IBS pathogenic mechanisms.

Gut commensal bacteria modulate synthesis of resolvin D1 in colonic tuft cells. Decreased synthesis of colonic resolvin D1 may contribute to the development of pain in patients with irritable bowel syndrome with diarrhea.

Objective
Recent studies have provided insights into the gut microbiota in autism spectrum disorder (ASD); however, these studies were restricted owing to limited sampling at the unitary stage of childhood. Herein, we aimed to reveal developmental characteristics of gut microbiota in a large cohort of subjects with ASD combined with interindividual factors impacting gut microbiota.

Design
A large cohort of 773 subjects with ASD (aged 16 months to 19 years), 429 neurotypical (NT) development subjects (aged 11 months to 15 years) were emolyed to determine the dynamics change of gut microbiota across different ages using 16S rRNA sequencing.

Result
In subjects with ASD, we observed a distinct but progressive deviation in the development of gut microbiota characterised by persistently decreased alpha diversity, early unsustainable immature microbiota, altered aboudance of 20 operational taxonomic units (OTUs), decreased taxon detection rate and 325 deregulated microbial metabolic functions with age-dependent patterns. We further revealed microbial relationships that have changed extensively in ASD before 3 years of age, which were associated with the severity of behaviour, sleep and GI symptoms in the ASD group. This analysis demonstrated that a signature of the combination of 2 OTUs, Veillonella and Enterobacteriaceae, and 17 microbial metabolic functions efficiently discriminated ASD from NT subjects in both the discovery (area under the curve (AUC)=0.86), and validation 1 (AUC=0.78), 2 (AUC=0.82) and 3 (AUC=0.67) sets.

Conclusion
Our large cohort combined with clinical symptom analysis highlights the key regulator of gut microbiota in the pathogenesis of ASD and emphasises the importance of monitoring and targeting the gut microbiome in future clinical applications of ASD.

In celiac disease, bacterial composition and function differ according to gut location.

Introduction
Several studies have demonstrated dysbiosis in irritable bowel syndrome (IBS). Therefore, faecal microbiota transplantation, whose effect and safety have been proven in Clostridioides difficile infections, may hold promise in other conditions, including IBS. Our study will examine the effectiveness of stool transfer with artificially increased microbial diversity in IBS treatment.

Methods and analysis
A three-group, double-blind,randomised, cross-over, placebo-controlled study of two pairs of gut microbiota transfer will be conducted in 99 patients with diarrhoeal or mixed type of IBS. Patients aged 18–65 will be randomised into three equally sized groups: group A will first receive two enemas of study microbiota mixture (deep-frozen stored stool microbiota mixed from eight healthy donors); after 8 weeks, they will receive two enemas with placebo (autoclaved microbiota mixture), whereas group B will first receive placebo, then microbiota mixture. Finally, group C will receive placebos only. The IBS Severity Symptom Score (IBS-SSS) questionnaires will be collected at baseline and then at weeks 3, 5, 8, 11, 13, 32. Faecal bacteriome will be profiled before and regularly after interventions using 16S rDNA next-generation sequencing. Food records, dietary questionnaires, anthropometry, bioimpedance, biochemistry and haematology workup will be obtained at study visits during the follow-up period. The primary outcome is the change in the IBS-SSS between the baseline and 4 weeks after the intervention for each patient compared with placebo. Secondary outcomes are IBS-SSS at 2 weeks after the intervention and 32 weeks compared with placebo and changes in the number of loose stools, Bristol stool scale, abdominal pain and bloating, anthropometric parameters, psychological evaluation and the gut microbiome composition.

Ethics and dissemination
The study was approved by the Ethics Committee of Thomayer University Hospital, Czechia (G-18-26); study results will be published in peer-reviewed journals and presented at international conferences and patient group meetings.

Trial registration number
NCT04899869.

Stroke, Ahead of Print. Besides damaging the brain, stroke causes systemic changes, including to the gastrointestinal system. A growing body of evidence supports the role of the gut and its microbiota in stroke, stroke prognosis, and recovery. The gut microbiota can increase the risk of a cerebrovascular event, playing a role in the onset of stroke. Conversely, stroke can induce dysbiosis of the gut microbiota and epithelial barrier integrity. This has been proposed as a contributor to systemic infections. In this review, we describe the role of the gut microbiota, microbiome and microbiota-derived metabolites in experimental and clinical stroke, and their potential use as therapeutic targets. Fourteen clinical studies have identified 62 upregulated (eg,Streptococcus,Lactobacillus, Escherichia) and 29 downregulated microbial taxa (eg,Eubacterium, Roseburia) between stroke and healthy participants. The majority found that stroke patients have reduced gut microbiome diversity. However, other nonbacterial microorganisms are yet to be studied. In experimental stroke, severity is dependent on gut microbiome composition, whereas the latter can greatly change with antibiotics, age, and diet. Consumption of foods rich in choline and L-carnitine are positively associated with stroke onset via production of trimethylamine N-oxide in experimental and clinical stroke. Conversely, in mice, consumption of dietary fiber improves stroke outcome, likely via gut microbiota–derived metabolites called short-chain fatty acids, such as acetate, propionate, and butyrate. The majority of the evidence, however, comes from experimental studies. Clinical interventions targeted at gut microbiota–derived metabolites as new therapeutic opportunities for stroke prevention and treatment are warranted.

Stroke, Volume 53, Issue Suppl_1, Page A83-A83, February 1, 2022. Microfold or membranous cells (M cells) are specialized antigen sampling cells residing in the epithelium of Peyer’s patches (PPs), the gut-associated lymphoid tissue in the small intestine. M cells are in continuous crosstalk with luminal microbes and host immune cells. The detrimental shift of the microbiota seen with aging and after stroke contribute to bacterial antigen translocation. This axis has emerged as an epicenter for post-stroke immune dysfunction and systemic infection. The role of M cells in the PPs as an initiation site for host mucosal immunity after stroke is undefined.Hypothesis:Stroke-induced gut dysbiosis and M cell ablation leads to impaired antigen sampling mechanisms and clearance of translocating bacteria in PPs after stroke. We used a 60-minute reversible middle cerebral artery occlusion model in young (8-10 wks) C57BL/6 male mice to investigate how brain ischemia affects M cells in the PPs. We performed microbiota transplants from the cecal contents of stroke mice to naïve age-matched recipients via oral gavage for three consecutive days before tissue harvest on day four. We determined that stroke-induced changes in gut microbiota alone can cause M cell dysfunction. We found that both the number of PPs and M cells decrease 24 hours after stroke (n=8/gp,p=0.0104andp=0.0054,respectively). Our imaging studies revealed disruption of tissue architecture and reduction in size of PPs after stroke. Microbiota transplant from stroke mice cecum to naïve recipients showed a similar effect on the number of PPs and M cells (n=10/gp,p=0.0568andp=0.0299). The decrease in the number of M cells after microbiota transplantation was associated with immune dysregulation in the PPs, such as a reduction in the number of regulatory T cells (n=5/gp,p=0.0084). This is the first study that specifically examined M cells in a mouse model of stroke. Our results show that 1) stroke reduces the number of PPs and M cells and 2) stroke-induced gut dysbiosis can independently reduce the number of PPs and likely M cells and may regulate gut-originated immune responses after stroke. Future studies are needed to understand the effects of stroke-induced dysbiosis on M cell-mediated antigen processing in the gut and their immunoregulatory functions.