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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]

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]

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]