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Simple Summary: Neoadjuvant chemotherapy (NAC) followed by radical gastrectomy is the standard approach for locally advanced gastric cancer (GC) in the West. This study investigated microbiome changes throughout GC treatment, including NAC and gastrectomy. A longitudinal observational design was employed, analyzing gut microbiome composition, fecal calprotectin, and gut permeability markers (LBP, sCD14) at baseline, post-NAC, and post-gastrectomy in 38 patients. Results indicated that NAC did not alter gut microbiome composition at the phylum level, whereas gastrectomy increased Bacteroidetes and Proteobacteria and decreased Firmicutes and Actinobacteria. NAC alone did not affect alpha or beta diversity; however, combining NAC with gastrectomy led to significant diversity changes. Post-gastrectomy microbiome analysis revealed an enrichment of oralization-associated bacteria, including Escherichia-Shigella, Streptococcus equinus, and members of the Enterobacteriaceae family. These findings suggest that gut microbiome alterations in GC treatment are primarily driven by gastrectomy rather than NAC, resulting in long-term oralization-associated shifts. Background/Objectives: Neoadjuvant chemotherapy (NAC) followed by radical gastrectomy is the current standard approach for locally advanced gastric cancer (GC) in the West. Both NAC and gastrectomy can significantly influence the gut microbiome, potentially leading to clinically significant changes. However, no longitudinal studies to date support this hypothesis. This study investigates gut microbiome changes throughout GC treatment, including NAC and gastrectomy. Methods: This longitudinal observational study included GC patients undergoing NAC followed by gastrectomy. Fecal microbiome composition, intestinal inflammation (fecal calprotectin), and gut permeability (LBP, sCD14) markers were investigated at baseline, after NAC, and after gastrectomy. Results: A total of 38 patients were included in the study. The results showed that NAC did not affect the gut microbiome composition at the phylum level. In contrast, radical gastrectomy led to an increased abundance of Bacteroidetes and Proteobacteria and a decreased abundance of Firmicutes and Actinobacteria. Furthermore, NAC alone did not impact alpha or beta diversity, while a combination of NAC and gastrectomy significantly influenced both. After gastrectomy, the gut microbiome composition analysis also revealed enrichment of oralization-associated bacterial species such as Escherichia-Shigella, Streptococcus equinus, uncultured Streptococcus species, and species from the Enterobacteriaceae family. Intestinal inflammation and gut permeability markers did not significantly change throughout the treatment. Conclusions: The radical treatment of advanced GC with NAC and radical surgery has long-term effects on the gut microbiome, characterized by gut microbiome oralization. These sustained alterations primarily stem from the radical gastrectomy rather than the NAC. Since previous studies have linked oralization-associated dysbiosis to various gastrointestinal symptoms, this study highlights the gut microbiome as a potential therapeutic target to enhance the quality of life in long-term survivors following gastrectomy. [ABSTRACT FROM AUTHOR]

Background: The novel coronavirus (SARS-CoV-2) led to gastrointestinal manifestations in up to 50% of cases, with diarrhea being common, and probiotics have been suggested as a potential treatment. Aim: This study aimed to assess changes in the microbiome and the effects of a multispecies probiotic in patients with COVID-19 in home quarantine through a fully remote telemedical approach. Methods: Thirty patients were randomized to receive either the Ecologic AAD probiotic (Winclove Probiotics, Amsterdam, The Netherlands), on the market as OMNi-BiOTiC 10 (Allergosan, Austria), or a placebo for 30 days in a 2:1 ratio. Respiratory and gastrointestinal symptoms were monitored in 2–10-day intervals via online surveys, and five stool samples were collected during the 30-day study period for microbiome and metabolomics analyses. Twenty-four healthy volunteers served as controls. Results: Of the 30 patients, 26 completed this study (10 placebo, 16 probiotic). Patients reported respiratory symptoms and a diminished gastrointestinal quality of life, both of which improved significantly during the study period, irrespective of the intervention. Compared to controls, infected patients showed significant alterations in the fecal microbiome (p = 0.002), including an increase in Bacteroidetes and decreases in Christensenellaceae, Ruminococcaceae, and Gammaproteobacteria, along with metabolomic changes. Probiotic treatment significantly modulated the patients' microbiome beta diversity (p = 0.001) and introduced the Enterococcus faecium W54 strain. Symptoms, COVID-19-related taxa, and the fecal metabolome were not affected by the intervention. Conclusions: Patients with mild COVID-19 disease in home quarantine exhibited respiratory symptoms, a reduced gastrointestinal quality of life, and changes in the fecal microbiome and metabolome. [ABSTRACT FROM AUTHOR]

Background: The gut–lung axis could be a potential therapeutic target for improving post-acute COVID-19 symptoms, and probiotics have been proposed as possible modulators. Aim: We conducted a pilot study to understand alterations in the gut–lung axis and to explore the effects of a probiotic in post-acute COVID-19 disease. Methods: We included patients after severe COVID-19 disease (sCOV, n = 21) in a randomized, placebo-controlled trial to test the effect of a probiotic (Pro-Vi 5, Institute Allergosan, Graz, Austria) in a six-month intervention and used patients after mild disease (mCOV, n = 10) as controls, to compare the intestinal microbiome, metabolome, and patient-reported outcomes and biomarkers along the gut–lung axis at baseline and throughout probiotic intervention. Results: Compared to mCOV patients, sCOV patients showed lower microbial richness, which was significantly improved by probiotic intervention. A reorganization of Ruminococcaceae and Lachnospiraceae taxa was observed in sCOV patients but remained unaffected by the intervention. Serum metabolome showed a dysregulation of lipoproteins in accordance with higher BMI and comorbidities in sCOV patients. HDL and LDL fractions/components were temporarily decreased in the probiotic group. Stool metabolome was altered at baseline in sCOV patients and an increase in L-DOPA after 3 months and butyrate after 6 months of intervention could be observed. Probiotics partially improved reduced quality of life and modulated altered immune responses in sCOV patients. Increased intestinal permeability at baseline remained unaffected. Conclusion: The study provides evidence of long-term alterations of the gut–lung axis after severe COVID-19 infection and suggests that probiotics can modulate the biomarkers of the gut–lung axis. [ABSTRACT FROM AUTHOR]

Background: Postoperative complications after colorectal cancer surgery have been linked to the gut microbiome. However, the impact of mechanical bowel preparation using oral preparation agents or rectal enema on postoperative infections remains poorly understood. This study aimed to compare the impact of oral preparation and rectal enema on the gut microbiome and postoperative complications. Methods: This open-label pilot RCT was conducted at the National Cancer Institute, Vilnius, Lithuania. Patients with left-side colorectal cancer scheduled for elective resection with primary anastomosis were randomized 1 : 1 to preoperative mechanical bowel preparation with either oral preparation or rectal enema. Stool samples were collected before surgery, and on postoperative day 6 and 30 for 16S rRNA gene sequencing analysis. The primary outcome was difference in β-diversity between groups on postoperative day 6. Results: Forty participants were randomized to oral preparation (20) or rectal enema (20). The two groups had similar changes in microbiome composition, and there was no difference in β-diversity on postoperative day 6. Postoperative infections occurred in 12 patients (32%), without differences between the study groups. Patients with infections had an increased abundance of bacteria from the Actinomycetaceae family, Actinomyces genus, Sutterella uncultured species, and Enterococcus faecalis species. Conclusion: Mechanical bowel preparation with oral preparation or rectal enema resulted in similar dysbiosis. Patients who experienced postoperative infections exhibited distinct gut microbiome compositions on postoperative day 6, characterized by an increased abundance of bacteria from the Actinomycetaceae family, Actinomyces genus, Sutterella uncultured species, and Enterococcus faecalis species. Registration number: NCT04013841 (http://www.clinicaltrials.gov). Postoperative complications after colorectal cancer surgery have been linked to the gut microbiome, but the impact of mechanical bowel preparation (MBP) using oral preparation agents (OP) or rectal enema (RE), on postoperative infections remains poorly understood. This study aimed to compare the impact of OP and RE on the gut microbiome and postoperative complications. MBP with OP and RE resulted in similar dysbiosis. Patients who experienced postoperative infections exhibited distinct gut microbiome compositions on postoperative day 6, characterized by an increased abundance of bacteria from the Actinomycetaceae family, Actinomyces genus, Sutterella uncultured species, and Enterococcus faecalis species. [ABSTRACT FROM AUTHOR]

Simple Summary: This review aims to improve our understanding of gastrointestinal tract cancer and the side effects of cancer treatment by using advanced in vitro systems. Traditional models like cell cultures and animal studies provide valuable insights but have limitations in replicating the complexity of human disease and raise ethical concerns. By focusing on bioreactor-based in vitro systems, which can mimic the physical and chemical environment of the gastrointestinal tract, this study aims to provide more accurate models for studying cancer and its treatment side effects. These advancements could lead to better insights into disease mechanisms, potentially improving treatment strategies and benefiting the broader research community. Human diseases are multifaceted, starting with alterations at the cellular level, damaging organs and their functions, and disturbing interactions and immune responses. In vitro systems offer clarity and standardisation, which are crucial for effectively modelling disease. These models aim not to replicate every disease aspect but to dissect specific ones with precision. Controlled environments allow researchers to isolate key variables, eliminate confounding factors and elucidate disease mechanisms more clearly. Technological progress has rapidly advanced model systems. Initially, 2D cell culture models explored fundamental cell interactions. The transition to 3D cell cultures and organoids enabled more life-like tissue architecture and enhanced intercellular interactions. Advanced bioreactor-based devices now recreate the physicochemical environments of specific organs, simulating features like perfusion and the gastrointestinal tract's mucus layer, enhancing physiological relevance. These systems have been simplified and adapted for high-throughput research, marking significant progress. This review focuses on in vitro systems for modelling gastrointestinal tract cancer and the side effects of cancer treatment. While cell cultures and in vivo models are invaluable, our main emphasis is on bioreactor-based in vitro modelling systems that include the gut microbiome. [ABSTRACT FROM AUTHOR]

Plastic particles smaller than 5 mm, referred to as Microplastics, pose health risks, like metabolic, immunological, neurological, reproductive, and carcinogenic effects, after being ingested. Smaller plastic particles are more likely to be absorbed by human cells, with nanoplastics showing higher potential for cellular damage, including DNA fragmentation and altered protein functions. Micro- and nanoplastics (MNPs) affect the gastrointestinal tract by altering the microbial composition, they could influence digestive enzymes, and possibly disrupt mucus layers. In the stomach, they potentially interfere with digestion and barrier functions, while in the intestines, they could increase permeability via inflammation and tissue disruption. MNPs can lead to microbial dysbiosis, leading to gastrointestinal symptoms. By activating inflammatory pathways, altering T cell functions and affecting dendritic cells and macrophages, immune system homeostasis could possibly be disrupted. Probiotics offer potential strategies to alleviate plastic effects, by either degrading plastic particles or directly countering health effects. We compared genetic sequences of probiotics to the genome of known plastic degraders and concluded that no probiotic bacteria could serve the role of plastic degradation. However, probiotics could directly mitigate MNP-health effects. They can restore microbial diversity, enhance the gut barrier, regulate bile acid metabolism, reduce inflammation, regulate insulin balance, and counteract metabolic disruptions. Antioxidative properties protect against lipid peroxidation and MNP-related reproductive system damage. Probiotics can also bind and degrade toxins, like heavy metals and bisphenol A. Additionally, bacteria could be used to aggregate MNPs and reduce their impact. Therefore, probiotics offer a variety of strategies to counter MNP-induced health effects., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: N.S. is employee of Institut AllergoSan (Institut AllergoSan manufactures and markets probiotics). M.H. and W.M. are employees of Winclove Probiotics (Winclove Probiotics manufactures and markets probiotics). The content of this study was neither influenced nor constrained by this fact. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)