Gut microbial subtypes and clinicopathological value for colorectal cancer.

BACKGROUND: Gut bacteria are related to colorectal cancer (CRC) and its clinicopathologic characteristics. OBJECTIVE: To develop gut bacterial subtypes and explore potential microbial targets for CRC. METHODS: Stool samples from 914 volunteers (376 CRCs, 363 advanced adenomas, and 175 normal controls) were included for 16S rRNA sequencing. Unsupervised learning was used to generate gut microbial subtypes. Gut bacterial community composition and clustering effects were plotted. Differences of gut bacterial abundance were analyzed. Then, the association of CRC-associated bacteria with subtypes and the association of gut bacteria with clinical information were assessed. The CatBoost models based on gut differential bacteria were constructed to identify the diseases including CRC and advanced adenoma (AA). RESULTS: Four gut microbial subtypes (A, B, C, D) were finally obtained via unsupervised learning. The characteristic bacteria of each subtype were Escherichia-Shigella in subtype A, Streptococcus in subtype B, Blautia in subtype C, and Bacteroides in subtype D. Clinical information (e.g., free fatty acids and total cholesterol) and CRC pathological information (e.g., tumor depth) varied among gut microbial subtypes. Bacilli, Lactobacillales, etc., were positively correlated with subtype B. Positive correlation of Blautia, Lachnospiraceae, etc., with subtype C and negative correlation of Coriobacteriia, Coriobacteriales, etc., with subtype D were found. Finally, the predictive ability of CatBoost models for CRC identification was improved based on gut microbial subtypes. CONCLUSION: Gut microbial subtypes provide characteristic gut bacteria and are expected to contribute to the diagnosis of CRC.

Fecal let-7b and miR-21 directly modulate the intestinal microbiota, driving chronic inflammation.

Inflammatory bowel diseases (IBD) etiology is multifactorial. Luminal microRNAs (miRNAs) have been suspected to play a role in the promotion of chronic inflammation, but the extent to which fecal miRNAs are interacting with the intestinal ecosystem in a way that contribute to diseases, including IBD, remains unknown. Here, fecal let-7b and miR-21 were found elevated, associated with inflammation, and correlating with multiple bacteria in IBD patients and IL-10-/- mice, model of spontaneous colitis. Using an in vitro microbiota modeling system, we revealed that these two miRNAs can directly modify the composition and function of complex human microbiota, increasing their proinflammatory potential. In vivo investigations revealed that luminal increase of let-7b drastically alters the intestinal microbiota and enhances macrophages' associated proinflammatory cytokines (TNF, IL-6, and IL-1ß). Such proinflammatory effects are resilient and dependent on the bacterial presence. Moreover, we identified that besides impairing the intestinal barrier function, miR-21 increases myeloperoxidase and antimicrobial peptides secretion, causing intestinal dysbiosis. More importantly, in vivo inhibition of let-7b and miR-21 with anti-miRNAs significantly improved the intestinal mucosal barrier function and promoted a healthier host-microbiota interaction in the intestinal lining, which altogether conferred protection against colitis. In summary, we provide evidence of the functional significance of fecal miRNAs in host-microbiota communication, highlighting their therapeutic potential in intestinal inflammation and dysbiosis-related conditions, such as IBD.

Anastomotic leak occurs independently from microbiota shifts associated with surgical bowel preparation.

Following bowel surgery, infectious complications, including anastomotic leak (AL), remain major sources of morbidity and mortality. Bowel preparation is often administered with the assumption that gut decontamination reduces post-surgical complications. In this study, we tested this hypothesis using a murine model of colon surgery. The mice were fed either regular chow or a high-fat, high-sugar Western diet. The day before surgery, the mice received one of four interventions: water (control), mechanical bowel preparation (MBP), oral antibiotics (OA), or both MBP and OA. We found no differences in the rates of AL among the experimental groups, and diet did not appear to affect the outcomes. Exploratory analyses showed changes in the gut microbiome consistent with the different treatments, but investigations of fecal short-chain fatty acids and RNA sequencing of colonic tissue did not reveal specific effects of the treatments or the presence of AL. However, we did identify bacterial genera that may be causally associated with AL and developed a predictive index from stool samples as a marker for the presence of AL. Future research is needed to identify and validate a microbial predictive tool and to uncover the microbial-driven mechanisms that lead to AL.

Conventional Therapy Combined With Quxie Capsule Modulating Gut Microbiome in Metastatic Colorectal Cancer Patients With the Third or Above Line Setting: Result From an Investigator-Initiated, Open-Label, Single-Arm, Phase II Study.

BACKGROUND: In patients with metastatic colorectal cancer (mCRC), Quxie Cap-sule (QX)-a combination of conventional therapy (including chemotherapy, targeted therapy or supportive care)-has shown a significant overall survival benefit compared with placebo and might have the property of dual effects of antitumor and immunity enhancement, both mediated by the microbiome. In preclinical models, QX has also shown activity against colorectal cancer. This study aimed to describe how the aforementioned effects of QX look after when focusing on the patients in third or above line setting. METHODS: A Simon's Minimax two-stage phase II design was used in this study, which enrolled mCRC patients who progressed after second-line treatment. Patients received conventional therapy plus QX until disease progression or unacceptable toxicity. Before and after 1-month intervention, we collected patients' stool samples for microbiome analysis by 16s rRNA sequencing approaches. And the microbiome analysis before and after 1-month intervention was done through bioinformation analysis platform. RESULTS: Fifteen patients were enrolled and gut microbiome were analyzed from 7 of 10 patients that with PFS over 3.7 months. Microbiome community analysis on genus level showed that the proportion of Lachnospiraceae_UCG-001 (0.04% vs 1.06%, P = .02249) significantly increased after conventional therapy plus QX while the proportion of Alistipes (2.96% vs 1.35%, P = .03461), Flavonifractor (0.04% vs 0.02%, P = .02249), Bifidobacterium (6.11% vs 1.14%, P = .02249) and Butyricimonas (0.24% vs 0.11%, P = .03603) significantly decreased after intervention . LEfSe analysis showed that after intervention, samples were highly related with unclassified-f-lachnospiraceae, Eubacterium and Lachnospiraceae_UCG-001. CONCLUSIONS: Decrease of gut bacteria with potential roles in carcinogenesis of colorectal cancer and increase in the abundance of gut anticancer bacteria such as Lachnospiraceae may partly explain how conventional therapy combined with QX can influence carcinogenesis and tumor progression in colon cancer. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2100053874).

Rifaximin ameliorates influenza A virus infection-induced lung barrier damage by regulating gut microbiota.

Prior research has indicated that the gut-lung-axis can be influenced by the intestinal microbiota, thereby impacting lung immunity. Rifaximin is a broad-spectrum antibacterial drug that can maintain the homeostasis of intestinal microflora. In this study, we established an influenza A virus (IAV)-infected mice model with or without rifaximin supplementation to investigate whether rifaximin could ameliorate lung injury induced by IAV and explore the molecular mechanism involved. Our results showed that IAV caused significant weight loss and disrupted the structure of the lung and intestine. The analysis results of 16S rRNA and metabolomics indicated a notable reduction in the levels of probiotics Lachnoclostridium, Ruminococcaceae_UCG-013, and tryptophan metabolites in the fecal samples of mice infected with IAV. In contrast, supplementation with 50 mg/kg rifaximin reversed these changes, including promoting the repair of the lung barrier and increasing the abundance of Muribaculum, Papillibacter and tryptophan-related metabolites content in the feces. Additionally, rifaximin treatment increased ILC3 cell numbers, IL-22 level, and the expression of RORγ and STAT-3 protein in the lung. Furthermore, our findings demonstrated that the administration of rifaximin can mitigate damage to the intestinal barrier while enhancing the expression of AHR, IDO-1, and tight junction proteins in the small intestine. Overall, our results provided that rifaximin alleviated the imbalance in gut microbiota homeostasis induced by IAV infection and promoted the production of tryptophan-related metabolites. Tryptophan functions as a signal to facilitate the activation and movement of ILC3 cells from the intestine to the lung through the AHR/STAT3/IL-22 pathway, thereby aiding in the restoration of the barrier. KEY POINTS: • Rifaximin ameliorated IAV infection-caused lung barrier injury and induced ILC3 cell activation. • Rifaximin alleviated IAV-induced gut dysbiosis and recovered tryptophan metabolism. • Tryptophan mediates rifaximin-induced ILC3 cell activation via the AHR/STAT3/IL-22 pathway.

Isolation and antimicrobial susceptibility profile of Salmonella species from slaughtered cattle carcasses and abattoir personnel at Dessie, municipality Abattoir, Northeast Ethiopia.

BACKGROUND: Antibiotic-resistant Salmonella is one of the main public health concerns in the world. Isolation of Salmonella in abattoirs has been considered the core source of infection in the community from meat. Still, there is limited information on the contamination rate of cattle carcasses. OBJECTIVE: This study aimed to document the occurrence and antimicrobial susceptibility profile of Salmonella species recovered from cattle carcass and abattoir personnel at Dessie, municipality abattoir, Northeast Ethiopia: METHODS: A total of 336 carcass swabs of abdomen, neck, and hind limb from cattle carcasses and 24 stool samples were collected from abattoir personnel using a systematic sampling method from February to April 2019. The collected samples were transported using Cary-Blair transport media and cultivated on Selenite cysteine F-broth, Brilliant green agar, and Xylose-lysine deoxycholate agar plates to isolate Salmonella species. Gram stain, colony morphology, and biochemical tests were performed to identify the isolated bacteria. An antimicrobial susceptibility test for Salmonella was performed using the Kirby-Bauer Disc Diffusion method. Descriptive statistics; both bivariable and multivariable logistic regression analysis was performed using SPSS version 25 software. P-value < 0.05 at 95% CI was considered statistically significant. RESULTS: The prevalence of salmonella species was 8%(27/336) from all samples.'The prevalence of Salmonella isolates in cattle carcass and abattoir personnel was 8%(25/312) and 8.3%(2/24) respectively. The antimicrobial test showed that Salmonella species were 100% resistant to ampicillin, 59.3% to trimethoprim-sulfamethoxazole, 59.3% to tetracycline, and 55.6% to amoxicillin/clavulanate. From the total antimicrobial tested bacteria, 81.5%(22/27) were resistant to three and above classes of antibiotics (drug classes). Unwashed knives, carcasses, and hands of butchers during slaughtering were significantly associated (p < 0.05) with Salmonella found in carcasses. CONCLUSIONS: Salmonella isolation rates from cattle carcasses were high, with the bacteria showing notable resistance to most tested antibiotics. Poor hygiene practices, unsanitized equipment, and unhygienic beef processing were contributing factors.

Links between fecal microplastics and parameters related to metabolic dysfunction-associated steatotic liver disease (MASLD) in humans: An exploratory study.

Microplastics (MPs) can persist in the environment and human body. Murine studies showed that exposure to MPs could cause metabolic dysregulation, contributing metabolic dysfunction-associated steatotic liver disease (MASLD) or steatohepatitis (MASH). However, research on the role of MPs in humans is limited. Thus, we aimed to assess links between human fecal MPs and liver histology, gene expression, immune cells and intestinal microbiota (IM). We included 6 lean healthy liver donors and 6 normal liver (obese) and 11 MASH patients. Overall, pre-BSx, we observed no significant differences in fecal MPs between groups. However, fecal MP fibers and total MPs positively correlated with portal and total macrophages and total killer T cells while total fecal MPs were positively correlated with natural killer cells. Additionally, 19 genes related to immune system and apoptosis correlated with fecal MPs at baseline. Fecal MP fibers correlated positively with fecal Bifidobacterium and negatively with Lachnospiraceae. Patients with MASH (n = 11) were re-assessed 12-months post-bariatric surgery (BSx) and we found that those with persistent disease (n = 4) had higher fecal MP fragments than those with normalized liver histology (n = 7). At 12-month post-BSx, MP fragments positively correlated with helper T cells and total MPs positively correlated with natural killer T cells and B cells. Our study is the first to look at 1) the role of MPs in MASH and its association with IM, immune cells and hepatic gene expression and 2) look at the role of MPs longitudinally in MASH persistence following BSx. Future research should further explore this relationship.

Review article: Faecal biomarkers for assessing small intestinal damage in coeliac disease and environmental enteropathy.

BACKGROUND: In coeliac disease and environmental enteropathy, dietary gluten and enteric infections cause reversible inflammation and morphological changes to the small intestinal mucosa that can be detected in biopsy samples obtained by endoscopy. However, there is a clear need for non-invasive biomarkers. Constant shedding of mucosal material into the bowel lumen and faeces, together with easy availability of stool, makes it an interesting sample matrix. AIMS: To conduct a systematic literature search and summarize the existing evidence for host mucosa-derived faecal biomarkers in evaluating small intestinal damage. METHODS: We searched for studies on PubMed (MEDLINE) until 1 March 2024. RESULTS: We identified 494 studies and included 35 original case-control and cohort studies. These assessed host mucosal transcripts and 14 other markers aiming specifically to reflect inflammation and cell-mediated, innate and gluten-induced immune responses. In coeliac disease, faecal calprotectin and anti-gliadin, tissue transglutaminase, endomysium and deamidated gliadin peptide antibodies were the most studied but with inconsistent results. Single studies reported positive findings about microRNA transcripts, ß-defensin-2, lipocalin-2, zonulin-related proteins and angiotensin-converting enzyme. In environmental enteropathy, a non-significant association was reported between calprotectin and urine lactulose/mannitol ratio; there were conflicting results for neopterin, myeloperoxidase and host transcripts. Single studies reported a positive association for lactoferrin, and a negative association for regenerating islet-derived protein 1. Studies comparing faecal markers against small intestinal biopsy findings were not identified in environmental enteropathy. CONCLUSIONS: Further studies are needed to determine reliable faecal markers as a proxy for small intestinal mucosal damage.

Metagenomic analysis of colonic tissue and stool microbiome in patients with colorectal cancer in a South Asian population.

BACKGROUND: The gut microbiome is thought to play an important role in the development of colorectal cancer (CRC). However, as the gut microbiome varies widely based on diet, we sought to investigate the gut microbiome changes in patients with CRC in a South Asian population. METHODS: The gut microbiome was assessed by 16s metagenomic sequencing targeting the V4 hypervariable region of the bacterial 16S rRNA in stool samples (n = 112) and colonic tissue (n = 36) in 112 individuals. The cohort comprised of individuals with CRC (n = 24), premalignant lesions (n = 10), healthy individuals (n = 50) and in those with diabetes (n = 28). RESULTS: Overall, the relative abundances of genus Fusobacterium (p < 0.001), Acinetobacter (p < 0.001), Escherichia-Shigella (p < 0.05) were significantly higher in gut tissue, while Romboutsia (p < 0.01) and Prevotella (p < 0.05) were significantly higher in stool samples. Bacteroides and Fusobacterium were the most abundant genera found in stool samples in patients with CRC. Patients with pre-malignant lesions had significantly high abundances of Christensenellaceae, Enterobacteriaceae, Mollicutes and Ruminococcaceae (p < 0.001) compared to patients with CRC, and healthy individuals. Romboutsia was significantly more abundant (p < 0.01) in stool samples in healthy individuals compared to those with CRC and diabetes. CONCLUSION: Despite marked differences in the Sri Lankan diet compared to the typical Western diet, Bacteroides and Fusobacterium species were the most abundant in those with CRC, with Prevotella species, being most abundant in many individuals. We believe these results pave the way for possible dietary interventions for prevention of CRC in the South Asian population.

Diagnostic application of the ColonFlag AI tool in combination with faecal immunochemical test in patients on an urgent lower gastrointestinal cancer pathway.

OBJECTIVE: Colorectal cancer (CRC) is the fourth most common cancer in the UK. Patients with symptoms suggestive of CRC should be referred for urgent investigation. However, gastrointestinal symptoms are often non-specific and there is a need for suitable triage tools to enable prioritisation of investigations. In this study, the performance of the faecal immunochemical test (FIT), anaemia and the artificial intelligence algorithm ColonFlag were retrospectively examined and evaluated for their potential clinical benefits in patients who had been referred on an urgent lower gastrointestinal cancer pathway. DESIGN: All patients aged over 40 years referred in a 12-month period were included. After 6 months, clinical outcomes were determined and the performance of the triage tests was evaluated. RESULTS: A total of 3822 patients completed investigations and received a diagnosis. 143 had CRC, 126 high-risk adenomas (HRA). ColonFlag would have missed 27 CRC and 29 HRA. Faecal haemoglobin (f-Hb) at a cut-off of 10 µg/g would have missed 10 CRC and 26 HRA; f-Hb in combination with anaemia would have missed 2 CRC and 14 HRA. Using f-Hb in combination with ColonFlag would have missed only 1 CRC and 5 HRA and would have reduced the need for urgent referral by over 400 patients. CONCLUSION: ColonFlag has potential to assist detection of CRC and HRA, alone where no faecal sample is present and in combination with FIT and to reduce the need for urgent referral.

Improved diagnostic efficiency of CRC subgroups revealed using machine learning based on intestinal microbes.

BACKGROUND: Colorectal cancer (CRC) is a common cancer that causes millions of deaths worldwide each year. At present, numerous studies have confirmed that intestinal microbes play a crucial role in the process of CRC. Additionally, studies have shown that CRC can be divided into several consensus molecular subtypes (CMS) based on tumor gene expression, and CRC microbiomes have been reported related to CMS. However, most previous studies on intestinal microbiome of CRC have only compared patients with healthy controls, without classifying of CRC patients based on intestinal microbial composition. RESULTS: In this study, a CRC cohort including 339 CRC samples and 333 healthy controls was selected as the discovery set, and the CRC samples were divided into two subgroups (234 Subgroup1 and 105 Subgroup2) using PAM clustering algorithm based on the intestinal microbial composition. We found that not only the microbial diversity was significantly different (Shannon index, p-value < 0.05), but also 129 shared genera altered (p-value < 0.05) between the two CRC subgroups, including several marker genera in CRC, such as Fusobacterium and Bacteroides. A random forest algorithm was used to construct diagnostic models, which showed significantly higher efficiency when the CRC samples were divided into subgroups. Then an independent cohort including 187 CRC samples (divided into 153 Subgroup1 and 34 Subgroup2) and 123 healthy controls was chosen to validate the models, and confirmed the results. CONCLUSIONS: These results indicate that the divided CRC subgroups can improve the efficiency of disease diagnosis, with various microbial composition in the subgroups.

Evaluation of novel synthetic peptides of avian hepatitis E virus ORF2 as vaccine candidate in chickens.

Avian hepatitis E virus (HEV) has resulted in significant economic losses in the poultry industry. There is currently no commercial vaccination available to prevent avian HEV infection. Previously, a novel epitope (601TFPS604) was discovered in the ORF2 protein of avian HEV. In this study, peptides were synthesized and assessed for their ability to provide immunoprotecting against avian HEV infection in poultry. Twenty-five Hy-Line Variety Brown laying hens were randomly divided into five groups; groups 1 to 3 respectively immunized with RLLDRLSRTFPS, PETRRLLDRLSR (irrelevant peptide control), or truncated avian HEV ORF2 protein (aa 339-606), while group 4 (negative control) was mock-immunized with PBS and group 5 (normal control) was not immunized or challenged. After the challenge, all hens in groups 2 and 4 showed seroconversion, fecal virus shedding, viremia, alanine aminotransferase (ALT) level increasing, liver lesions and HEV antigen in the liver. There were no pathogenic effects in other groups. Collectively, all of these findings showed that hens were completely protected against avian HEV infection when they were immunized with the peptide containing TFPS of the avian HEV ORF2 protein.

Crossroad between the sylvatic and domestic cycles of Mesocestoides litteratus: mesocestodiasis in dogs adopted from shelters in Türkiye.

This study aimed to report the presence of Mesocestoides litteratus in dogs adopted from shelters in Türkiye. Gravid segments were examined microscopically in the faeces of dogs from different shelters located in Ankara and Kirikkale provinces in the central region of Türkiye. Then, genomic DNA obtained from these segments, a 446-bp fragment of the mitochondrial cytochrome C oxidase subunit 1 gene, and a 350-bp fragment of mitochondrial 12S rRNA were amplified and sequenced. BLASTn search was performed. During light microscopic examination, an egg-filled paruterine organ was observed in the middle part of the segment. Thin-shelled, oval, 35-µm-diameter parasite eggs containing an oncosphere with three pairs of hooklets were observed. The gravid segments were determined as Mesocestoides spp. based on the appearance of the typical paruterine organ. PCR results supported our diagnosis; moreover, according to the BLAST results, it was detected that the species infecting two dogs was 98.01-100% similar to M. litteratus. Praziquantel-containing medication was administered to the infected dogs at a dosage of 5 mg/kg. Foxes act as the final host of M. litteratus and the parasite is prevalent in wildlife; however, these animals may disperse the parasite in urban life. Veterinarians need to be made more aware of this parasite, especially if the dogs are owned from shelters.

Enteric pathogens relationship with small bowel histologic features of environmental enteric dysfunction in a multicountry cohort study.

BACKGROUND: Environmental Enteric Dysfunction (EED) is an acquired disorder of asymptomatic altered gut function, the etiology of which is unknown. EED is postulated to be a major contributor to growth faltering in early childhood in regions where early-life enteropathogenic carriage is prevalent. Few studies have examined the critical organ (the upper small bowel) with enteropathogens in the evolution of small bowel disease. OBJECTIVES: The objective of this study was to determine if fecal enteropathogenic detection predicts subsequent EED histology. METHODS: Fecal samples were obtained from undernourished children aged <2 y without diarrhea enrolled in 3 cohort studies, who failed nutritional intervention and subsequently underwent endoscopy. Duodenal biopsies from 245 (Bangladesh n = 120, Pakistan n = 57, and Zambia n = 68) children were scored using a semiquantitative histologic grading protocol. Thirteen enteropathogens were sought in common across the 3 centers using TaqMan array cards (TAC) (Bangladesh and Pakistan) and the Luminex platform (Zambia). An additional 18 pathogens and 32 virulence loci were sought by TAC and included in sensitivity analyses restricted to TAC data. RESULTS: Multivariable linear regressions adjusting for study center, age at stool collection, and stool-to-biopsy interval demonstrated the following: 1) an association of norovirus and Shigella detection with subsequent enterocyte injury [ß 0.2 (95% CI: 0.1, 0.3); P = 0.002 and ß 0.2 (95% CI: 0.0, 0.3); P = 0.008, respectively], 2) association of Campylobacter with intraepithelial lymphocytes [ß 0.2 (95% CI: 0.0, 0.4); P = 0.046], and 3) association of Campylobacter and enterotoxigenic Escherichia coli with a summative EED histopathology index score [ß 4.2 (95% CI: 0.8, 7.7); P = 0.017 and ß 3.9 (95% CI: 0.5, 7.3); P = 0.027, respectively]. All but 2 of these associations (Shigella-enterocyte injury and Campylobacter-index score) were also demonstrated in TAC-only sensitivity analyses, which identified additional associations between other pathogens, pathogen burden, or virulence loci primarily with the same histologic parameters. CONCLUSIONS: The detection of some enteropathogens in asymptomatic infections is associated with subsequent EED histopathology. These novel findings offer a basis for future EED etiology and pathogenesis studies.

Biomarker relationships with small bowel histopathology among malnourished children with environmental enteric dysfunction in a multicountry cohort study.

BACKGROUND: Validated biomarkers could catalyze environmental enteric dysfunction (EED) research. OBJECTIVES: Leveraging an EED histology scoring system, this multicountry analysis examined biomarker associations with duodenal histology features among children with EED. We also examined differences in 2-h compared with 1-h urine collections in the lactulose rhamnose (LR) dual sugar test. METHODS: Three cohorts of undernourished children unresponsive to nutrition intervention underwent esophagogastroduodenoscopy and duodenal biopsies. Histopathology scores were compared to fecal calprotectin (CAL), myeloperoxidase (MPO), neopterin (NEO), and urinary LR ratio and lactulose percentage recovery. Log-transformed biomarkers were used in linear regressions adjusted for age, center, and sample collection-biopsy time interval in multivariable models. RESULTS: Data on >1 biomarker were available for 120 Bangladeshi (CAL, MPO, NEO, and LR), 63 Pakistani (MPO, NEO, and LR), and 63 Zambian children (CAL). Median age at endoscopy was similar (19 mo) across centers. Median sample collection prior to endoscopy was consistent with each center's study design: 2 wk in Bangladesh (urine and stool) and Zambia (stool), and 6 (urine) and 11 (stool) mo in Pakistan. In multivariable models, intraepithelial lymphocytes were associated with CAL (exponentiated [exp.] coefficient: 1.19; 95% confidence interval [CI]: 1, 1.41), intramucosal Brunner's glands with MPO (exp. coefficient: 1.33; 95% CI: 1.05, 1.69) and NEO (exp. coefficient: 1.37; 95% CI: 1.1, 1.7), and chronic inflammation with NEO (exp. coefficient: 1.61; 95% CI: 1.17, 2.17). Intraepithelial lymphocytes were associated with lactulose % recovery (exp. coefficient: 1.22; 95% CI: 1.05, 1.41). LR recovery was substantially lower in 1-h collections than in 2-h collections. CONCLUSIONS: Four commonly used markers of enteric dysfunction were associated with specific histologic features. One-hour urine collection may be insufficient to reflect small bowel permeability in LR testing. While acknowledging the challenges with obtaining relevant tissue, these findings form the basis for further EED biomarker validation research.

Stool and blood metabolomics in the metabolic syndrome: a cross-sectional study.

INTRODUCTION/OBJECTIVES: Changes in the stool metabolome have been poorly studied in the metabolic syndrome (MetS). Moreover, few studies have explored the relationship of stool metabolites with circulating metabolites. Here, we investigated the associations between stool and blood metabolites, the MetS and systemic inflammation. METHODS: We analyzed data from 1,370 participants of the KORA FF4 study (Germany). Metabolites were measured by Metabolon, Inc. (untargeted) in stool, and using the AbsoluteIDQ® p180 kit (targeted) in blood. Multiple linear regression models, adjusted for dietary pattern, age, sex, physical activity, smoking status and alcohol intake, were used to estimate the associations of metabolites with the MetS, its components and high-sensitivity C-reactive protein (hsCRP) levels. Partial correlation and Multi-Omics Factor Analysis (MOFA) were used to investigate the relationship between stool and blood metabolites. RESULTS: The MetS was significantly associated with 170 stool and 82 blood metabolites. The MetS components with the highest number of associations were triglyceride levels (stool) and HDL levels (blood). Additionally, 107 and 27 MetS-associated metabolites (in stool and blood, respectively) showed significant associations with hsCRP levels. We found low partial correlation coefficients between stool and blood metabolites. MOFA did not detect shared variation across the two datasets. CONCLUSIONS: The MetS, particularly dyslipidemia, is associated with multiple stool and blood metabolites that are also associated with systemic inflammation. Further studies are necessary to validate our findings and to characterize metabolic alterations in the MetS. Although our analyses point to weak correlations between stool and blood metabolites, additional studies using integrative approaches are warranted.

A next-generation mt-sDNA test had 94% sensitivity for colorectal cancer and 91% specificity for advanced neoplasia.

SOURCE CITATION: Imperiale TF, Porter K, Zella J, et al; BLUE-C Study Investigators. Next-generation multitarget stool DNA test for colorectal cancer screening. N Engl J Med. 2024;390:984-993. 38477986.

Cockroach Blaptica dubia biodegrades polystyrene plastics: Insights for superior ability, microbiome and host genes.

The report demonstrated that a member of cockroach family, Blaptica dubia (Blattodea: Blaberidae) biodegraded commercial polystyrene (PS) plastics with Mn of 20.3 kDa and Mw of 284.9 kDa. The cockroaches digested up to 46.6 % of ingested PS within 24 h. The biodegradation was confirmed by the 13C isotopic shift of the residual PS in feces versus pristine PS (Δ Î´13C of 2.28 ‰), reduction of molecular weight and formation of oxidative functional groups in the residual PS. Further tests found that B.dubia cockroaches degraded all eight high purity PS microplastics with low to ultra-high molecular weights (MW) at 0.88, 1.20, 3.92, 9.55, 62.5, 90.9, 524.0, and 1040 kDa, respectively, with superior biodegradation ability. PS depolymerization/biodegradation pattern was MW-dependent. Ingestion of PS shifted gut microbial communities and elevated abundances of plastic-degrading bacterial genes. Genomic, transcriptomic and metabolite analyses indicated that both gut microbes and cockroach host contributed to digestive enzymatic degradation. PS plastic diet promoted a highly cooperative model of gut digestive system. Weighted gene co-expression network analysis revealed different PS degradation patterns with distinct MW profiles in B. dubia. These results have provided strong evidences of plastic-degrading ability of cockroaches or Blaberidae family and new understanding of insect and their microbe mediated biodegradation of plastics.

The DAV132 colon-targeted adsorbent does not interfere with plasma concentrations of antibiotics but prevents antibiotic-related dysbiosis: a randomized phase I trial in healthy volunteers.

The deleterious impact of antibiotics (ATB) on the microbiome negatively influences immune checkpoint inhibitors (ICI) response in patients with cancer. We conducted a randomized phase I study (EudraCT:2019-A00240-57) with 148 healthy volunteers (HV) to test two doses of DAV132, a colon-targeted adsorbent, alongside intravenous ceftazidime-avibactam (CZA), piperacillin-tazobactam (PTZ) or ceftriaxone (CRO) and a group without ATB. The primary objective of the study was to assess the effect of DAV132 on ATB plasma concentrations and both doses of DAV132 did not alter ATB levels. Secondary objectives included safety, darkening of the feces, and fecal ATB concentrations. DAV132 was well tolerated, with no severe toxicity and similar darkening at both DAV132 doses. DAV132 led to significant decrease in CZA or PTZ feces concentration. When co-administered with CZA or PTZ, DAV132 preserved microbiome diversity, accelerated recovery to baseline composition and protected key commensals. Fecal microbiota transplantation (FMT) in preclinical cancer models in female mice from HV treated with CZA or PTZ alone inhibited anti-PD-1 response, while transplanted samples from HV treated with ATB + DAV132 circumvented resistance to anti-PD-1. This effect was linked to activated CD8+ T cell populations in the tumor microenvironment. DAV132 represents a promising strategy for overcoming ATB-related dysbiosis and further studies are warranted to evaluate its efficacy in cancer patients.