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Dysbiosis of the gut microbiome has been associated with the pathogenesis of colorectal cancer (CRC). We profiled the microbiome of gut mucosal tissues from 18 CRC patients and 18 non-CRC controls of the UKM Medical Centre (UKMMC), Kuala Lumpur, Malaysia. The results were then validated using a species-specific quantitative PCR in 40 CRC and 20 non-CRC tissues samples from the UMBI-UKMMC Biobank. Parvimonas micra , Fusobacterium nucleatum , Peptostreptococcus stomatis and Akkermansia muciniphila were found to be over-represented in our CRC patients compared to non-CRC controls. These four bacteria markers distinguished CRC from controls (AUROC = 0.925) in our validation cohort. We identified bacteria species significantly associated (cut-off value of > 5 fold abundance) with various CRC demographics such as ethnicity, gender and CRC staging; however, due to small sample size of the discovery cohort, these results could not be further verified in our validation cohort. In summary, Parvimonas micra , Fusobacterium nucleatum , Peptostreptococcus stomatis and Akkermansia muciniphila were enriched in our local CRC patients. Nevertheless, the roles of these bacteria in CRC initiation and progression remains to be investigated.

Background Our study aimed to determine the effect of probiotic consumption containing six viable microorganisms of 30 × 10 10  cfu Lactobacillus and Bifidobacteria strains for six months on clinical outcomes and inflammatory cytokines (TNF-α, IFN-γ, IL-6, IL-10, IL-12, IL-17A, IL-17C and IL-22) in patients with colorectal cancer. Methods Fifty-two patients with colorectal cancer were randomized at four weeks after surgery to receive either a placebo ( n  = 25) or 30 billion colony-forming unit (CFU) of a mixture of six viable strains including 107 mg of Lactobacillus acidophilus BCMC® 12,130, Lactobacillus lactis BCMC® 12,451, Lactobacillus casei subsp BCMC® 12,313, Bifidobacterium longum BCMC® 02120, Bifidobacterium bifidum BCMC® 02290 and Bifidobacterium infantis BCMC® 02129 ( n  = 27). Patients were instructed to take the product orally twice daily for six months. Infection status, diarrhea or hospital admission were recorded throughout the study. Blood was taken pre- and post-intervention to measure TNF-α, IFN-γ, IL-6, IL-10, IL-12, IL-17A, IL-17C and IL-22 using ELISA multiplex kit. Results The majority of cases (~ 70%) were in Duke’s C colorectal cancer for both groups. No surgical infection occurred and no antibiotics were required. Chemotherapy induced diarrhea was observed in both groups. Significant reduction in the level of pro-inflammatory cytokine, TNF-α, IL-6, IL-10, IL-12, IL-17A, IL-17C and IL-22 were observed in CRC patients who received probiotics as compared to pre-treatment level ( P  < 0.05). However, there was no significant difference in the IFN-γ in both groups. Conclusions We have shown that probiotics containing six viable microorganisms of Lactobacillus and Bifidobacteria strains are safe to be consumed at four weeks after surgery in colorectal cancer patients and have reduced pro-inflammatory cytokines (except for IFN-gamma). Probiotic may modify intestinal microenvironment resulting in a decline in pro-inflammatory cytokines. Trial registration NCT03782428 ; retrospectively registered on 20th December 2018.

We determined the effectiveness of a multi-strain probiotic (Hexbio®) containing microbial cell preparation MCP®BCMC® on constipation symptoms and gut motility in PD patients with constipation. PD patients with constipation (ROME III criteria) were randomized to receive a multi-strain probiotic (Lactobacillus sp and Bifidobacterium sp at 30 X 109 CFU) with fructo-oligosaccaride or placebo (fermented milk) twice daily for 8 weeks. Primary outcomes were changes in the presence of constipation symptoms using 9 items of Garrigues Questionnaire (GQ), which included an item on bowel opening frequency. Secondary outcomes were gut transit time (GTT), quality of life (PDQ39-SI), motor (MDS-UPDRS) and non-motor symptoms (NMSS). Of 55 recruited, 48 patients completed the study: 22 received probiotic and 26 received placebo. At 8 weeks, there was a significantly higher mean weekly BOF in the probiotic group compared to placebo [SD 4.18 (1.44) vs SD 2.81(1.06); (mean difference 1.37, 95% CI 0.68, 2.07, uncorrected p<0.001)]. Patients in the probiotic group reported five times higher odds (odds ratio = 5.48, 95% CI 1.57, 19.12, uncorrected p = 0.008) for having higher BOF (< 3 to 3-5 to >5 times/week) compared to the placebo group. The GTT in the probiotic group [77.32 (SD55.35) hours] reduced significantly compared to placebo [113.54 (SD 61.54) hours]; mean difference -36.22, 95% CI -68.90, -3.54, uncorrected p = 0.030). The mean change in GTT was 58.04 (SD59.04) hour vs 20.73 (SD60.48) hours respectively (mean difference 37.32, 95% CI 4.00, 70.63, uncorrected p = 0.028). No between-groups differences were observed in the NMSS, PDQ39-SI, MDS-UPDRS II and MDS-UPDRS III scores. Four patients in the probiotics group experienced mild reversible side effects. This study showed that consumption of a multi-strain probiotic (Hexbio®) over 8 weeks improved bowel opening frequency and whole gut transit time in PD patients with constipation.

Gestational diabetes mellitus (GDM) is defined as impaired glucose tolerance recognized during pregnancy. GDM is associated with metabolic disorder phenotypes, such as obesity, low-grade inflammation, and insulin resistance. Following delivery, nearly half of the women with a history of GDM have persistent postpartum glucose intolerance and an increased risk of developing type 2 diabetes mellitus (T2DM), as much as 7-fold. The alarming upward trend may worsen the socioeconomic burden worldwide. Accumulating evidence strongly associates gut microbiota dysbiosis in women with GDM, similar to the T2DM profile. Several metagenomics studies have shown gut microbiota, such as Ruminococcaceae, Parabacteroides distasonis, and Prevotella, were enriched in women with GDM. These microbiota populations are associated with metabolic pathways for carbohydrate metabolism and insulin signaling, suggesting a potential “gut microbiota signature” in women with GDM. Furthermore, elevated expression of serum zonulin, a marker of gut epithelial permeability, during early pregnancy in women with GDM indicates a possible link between gut microbiota and GDM. Nevertheless, few studies have revealed discrepant results, and the interplay between gut microbiota dysbiosis and host metabolism in women with GDM is yet to be elucidated. Lifestyle modification and pharmacological treatment with metformin showed evidence of modulation of gut microbiota and proved to be beneficial to maintain glucose homeostasis in T2DM. Nonetheless, post-GDM women have poor compliance toward lifestyle modification after delivery, and metformin treatment remains controversial as a T2DM preventive strategy. We hypothesized modulation of the composition of gut microbiota with probiotics supplementation may reverse postpartum glucose intolerance in post-GDM women. In this review, we addressed gut microbiota dysbiosis and the possible mechanistic links between the host and gut microbiota in women with GDM. Furthermore, this review highlights the potential therapeutic use of probiotics in post-GDM women as a T2DM preventive strategy.

Treatment for non-alcoholic fatty liver disease (NAFLD) currently consists of lifestyle modifications such as a low-fat diet, weight loss, and exercise. The gut microbiota forms part of the gut–liver axis and serves as a potential target for NAFLD treatment. We investigated the effect of probiotics on hepatic steatosis, fibrosis, and biochemical blood tests in patients with NAFLD. At the small intestinal mucosal level, we examined the effect of probiotics on the expression of CD4+ and CD8+ T lymphocytes, as well as the tight junction protein zona occluden-1 (ZO-1). This was a randomized, double-blind, placebo-controlled trial involving ultrasound-diagnosed NAFLD patients (n = 39) who were supplemented with either a probiotics sachet (MCP® BCMC® strains) or a placebo for a total of 6 months. Multi-strain probiotics (MCP® BCMC® strains) containing six different Lactobacillus and Bifidobacterium species at a concentration of 30 billion CFU were used. There were no significant changes at the end of the study in terms of hepatic steatosis (probiotics: −21.70 ± 42.6 dB/m, p = 0.052 vs. placebo: −10.72 ± 46.6 dB/m, p = 0.29) and fibrosis levels (probiotics: −0.25 ± 1.77 kPa, p = 0.55 vs. placebo: −0.62 ± 2.37 kPa, p = 0.23) as measured by transient elastography. Likewise, no significant changes were found for both groups for the following parameters: LiverFAST analysis (steatosis, fibrosis and inflammation scores), alanine aminotransferase, total cholesterol, triglycerides, and fasting glucose. In the immunohistochemistry (IHC) analysis, no significant expression changes were seen for CD4+ T lymphocytes in either group (probiotics: −0.33 ± 1.67, p = 0.35 vs. placebo: 0.35 ± 3.25, p = 0.63). However, significant reductions in the expression of CD8+ T lymphocytes (−7.0 ± 13.73, p = 0.04) and ZO-1 (Z-score = −2.86, p = 0.04) were found in the placebo group, but no significant changes in the probiotics group. In this pilot study, the use of probiotics did not result in any significant clinical improvement in NAFLD patients. However, at the microenvironment level (i.e., the small intestinal mucosa), probiotics seemed to be able to stabilize the mucosal immune function and to protect NAFLD patients against increased intestinal permeability. Therefore, probiotics might have a complementary role in treating NAFLD. Further studies with larger sample sizes, a longer duration, and different probiotic strains are needed to evaluate the real benefit of probiotics in NAFLD.

Patients with irritable bowel syndrome (IBS) are increasingly presenting with a wide range of neuropsychiatric symptoms, such as deterioration in gastroenteric physiology, including visceral hypersensitivity, altered intestinal membrane permeability, and gastrointestinal motor dysfunction. Functional imaging of IBS patients has revealed several abnormalities in various brain regions, such as significant activation of amygdala, thinning of insular and anterior cingulate cortex, and increase in hypothalamic gray matter, which results in poor psychiatric and cognitive outcomes. Interrelations between the enteric and central events in IBS-related gastrointestinal, neurological, and psychiatric pathologies have compelled researchers to study the gut-brain axis—a bidirectional communication that maintains the homeostasis of the gastrointestinal and central nervous system with gut microbiota as the protagonist. Thus, it can be disrupted by any alteration owing to the gut dysbiosis or loss of diversity in microbial composition. Available evidence indicates that the use of probiotics as a part of a balanced diet is effective in the management of IBS and IBS-associated neurodegenerative and psychiatric comorbidities. In this review, we delineate the pathogenesis and complications of IBS from gastrointestinal and neuropsychiatric standpoints while also discussing the neurodegenerative events in enteric and central nervous systems of IBS patients and the therapeutic potential of gut microbiota-based therapy established on clinical and preclinical data.

Irritable bowel syndrome (IBS) is frequently linked with coexisting mental illnesses. Our previous study discovered that 32.1% of IBS patients had subthreshold depression (SD), placing them at higher risk of developing major depression. Gut microbiota modulation through psychobiotics was found to influence depression via the gut-brain axis. However, the efficacy of lessening depression among IBS patients remains ambiguous. The study’s aim was to investigate the roles of cultured milk drinks containing 10 9  cfu Lactobacillus acidophilus LA-5 and Lactobacillus paracasei L. CASEI-01 on depression and related variables among IBS participants with SD. A total of 110 IBS participants with normal mood (NM) and SD, were randomly assigned to one of four intervention groups: IBS-NM with placebo, IBS-NM with probiotic, IBS-SD with placebo, and IBS-SD with probiotic. Each participant was required to consume two bottles of cultured milk every day for a duration of 12 weeks. The following outcomes were assessed: depression risk, quality of life, the severity of IBS, and hormonal changes. The depression scores were significantly reduced in IBS-SD with probiotic and placebo from baseline (p < 0.001). Only IBS-SD with probiotic showed a significant rise in serotonin serum levels (p < 0.05). A significantly higher life quality measures were seen in IBS-SD with probiotic, IBS-SD with placebo, and IBS-NM with placebo (p < 0.05). All groups, both placebo and probiotic, reported significant improvement in IBS severity post-intervention with a higher prevalence of remission and mild IBS (p < 0.05). Dual strains lactobacillus -containing cultured milk drink via its regulation of relevant biomarkers, is a potential anti-depressive prophylactic agent for IBS patients at risk.

As we progress deeper into the digital age, the robust development and application of advanced artificial intelligence (AI) technology, specifically generative language models like ChatGPT (OpenAI), have potential implications in all sectors including medicine. This viewpoint article aims to present the authors’ perspective on the integration of AI models such as ChatGPT in clinical medicine and medical education. The unprecedented capacity of ChatGPT to generate human-like responses, refined through Reinforcement Learning with Human Feedback, could significantly reshape the pedagogical methodologies within medical education. Through a comprehensive review and the authors’ personal experiences, this viewpoint article elucidates the pros, cons, and ethical considerations of using ChatGPT within clinical medicine and notably, its implications for medical education. This exploration is crucial in a transformative era where AI could potentially augment human capability in the process of knowledge creation and dissemination, potentially revolutionizing medical education and clinical practice. The importance of maintaining academic integrity and professional standards is highlighted. The relevance of establishing clear guidelines for the responsible and ethical use of AI technologies in clinical medicine and medical education is also emphasized.

Global plastic waste production remains a critical environmental issue. Microplastics (MPs), plastic particles less than 5 mm, are now pervasive across ecosystems. Humans are exposed to MPs via ingestion, inhalation, and dermal contact raising concerns about their health impacts. This systematic review investigates the influence of MPs on the human gut microbiome, focusing on changes in microbial composition, diversity, and metabolic pathways based on 12 studies identified through Scopus and PubMed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Findings show that exposure to MPs such as polyethylene (PE), polystyrene (PS), polyethylene terephthalate (PET), polyvinyl chloride (PVC), and polylactic acid (PLA), induces gut dysbiosis, marked by a loss of beneficial genera, and enrichment of pathogenic species. MPs also impair short-chain fatty acid (SCFA) production, alter metabolic functions, and modulate immune pathways, contributing to intestinal diseases, metabolic syndrome, and chronic inflammation. The extent of disruption is influenced by MP-specific properties such as type, size, and concentration. These results suggest that MPs are emerging environmental risk factors with tangible implications for human health. To fully understand the health concerns associated with MPs long-term, human-relevant studies with standardized methodologies are urgently needed to define safe exposure levels and guide policies aimed at reducing MP-related health risks. Graphical Abstract

Abstract Background: The use of intestinal ultrasound (IUS) in the management of inflammatory bowel disease (IBD) is emerging. We aim to determine the performance of IUS in the assessment of disease activity in IBD. Methods: This is a prospective cross-sectional study of IUS performed on IBD patients in a tertiary centre. IUS parameters including intestinal wall thickness, loss of wall stratification, mesenteric fibrofatty proliferation, and increased vascularity were compared with endoscopic and clinical activity indices. Results: Among the 51 patients, 58.8% were male, with a mean age of 41 years. Fifty-seven percent had underlying ulcerative colitis with mean disease duration of 8.4 years. Against ileocolonoscopy, IUS had a sensitivity of 67% (95% confidence interval (CI): 41-86) for detecting endoscopically active disease. It had high specificity of 97% (95% CI: 82-99) with positive and negative predictive values of 92% and 84%, respectively. Against clinical activity index, IUS had a sensitivity of 70% (95% CI: 35-92) and specificity of 85% (95% CI: 70-94) for detecting moderate to severe disease. Among individual IUS parameters, presence of bowel wall thickening (>3 mm) had the highest sensitivity (72%) for detecting endoscopically active disease. For per-bowel segment analysis, IUS (bowel wall thickening) was able to achieve 100% sensitivity and 95% specificity when examining the transverse colon. Conclusions: IUS has moderate sensitivity with excellent specificity in detecting active disease in IBD. IUS is most sensitive in detecting a disease at transverse colon. IUS can be employed as an adjunct in the assessment of IBD.