Editorial: The microbiome in the development of gastrointestinal diseases

The human microbiome, a complex and dynamic ecosystem composed of trillions of microorganisms residing in various body sites, plays a critical role in maintaining health and homeostasis. Recent research has increasingly focused on the gut microbiome (GM) due to its significant influence on gastrointestinal (GI) health and its involvement in the development of various GI diseases. This editorial synthesizes findings from 16 manuscripts, including 11 original research articles, 3 reviews, 1 mini-review, and 1 systematic review, authored by a diverse group of 109 researchers from countries including China, Croatia, Finland, France, Germany, India, Iran, Kazakhstan, Poland, Portugal, Romania, Slovakia, and Sweden. Collectively, these studies highlight the intricate relationships between gut microbiome composition and several GI disorders, including colorectal cancer (CRC), inflammatory bowel disease (IBD), diverticular disease, small intestinal bacterial overgrowth (SIBO), and metabolic dysfunction-associated fatty liver disease (MAFLD) (Figure 1). The evidence presented reveals how dysbiosis (microbial communities' imbalance) can contribute to inflammation, impaired immune responses, and altered metabolic functions that predispose individuals to these diseases. Furthermore, new insights into the gut-brain axis are revealing how GM can influence not only local intestinal health, but also systemic conditions affecting other organs. Interventions aimed at modulating the microbiome composition and/or function by prebiotics, probiotics, or dietary changes have shown promise in alleviating symptoms and improving treatment outcomes in patients with GI diseases. As our understanding of the GM role expands through this extensive body of work in multiple international contexts, it becomes increasingly clear that targeting the microbial balance may offer innovative strategies for the prevention and effective management of GI diseases.The study by Magnan et al. investigates the relationship between GM, bacterial translocation, and acute GI injury in critically ill patients with septic shock. The study involved 60 adults over seven days and assessed changes in GM diversity and their correlation with clinical outcomes. Results show a significant decrease in bacterial diversity and richness from day 0 to day 7, with lower alpha diversity associated with higher SOFA scores. An increase in Enterococcus species was observed alongside a decrease in beneficial bacteria such as Bifidobacterium. In addition, increased levels of bacterial translocation were observed at both admission and day 7 compared to healthy controls (HC), suggesting that gut inflammation may promote bacterial translocation into the circulation. Mortality analysis revealed that non-survivors had lower GM diversity on admission. Certain genera such as Mogibacteriaceae were more abundant in non-survivors, while others such as Escherichia decreased over time. The increase in Enterococcus during hospitalization correlated with worse outcomes. The study concludes that dysbiosis and bacterial translocation significantly influence acute GI severity and mortality risk in septic shock patients, suggesting further exploration of therapeutic strategies targeting GM to improve patient outcomes.Yang et al. present a bibliometric analysis of research related to Helicobacter pylori (HP) and gastric cancer (GC) from 2003 to 2022. Their study aims to assess scientific output, identify influential papers, summarize current knowledge, and explore emerging trends in the field. A total of 1,970 papers were retrieved, showing an increasing trend in publications over the years. China and Japan emerged as the leading contributors, with Vanderbilt University notable for its high output. Key authors include Richard M. Peek Jr. and Maria B. Piazuelo, both from Vanderbilt University. The journal "Helicobacter" published the most papers, while "Gastroenterology" had the highest number of citations. The analysis highlights relevant themes such as the HP role in gastric tumorigenesis, its pathogenesis in relation to GC and the mechanisms by which HP affects GC development. Emerging areas for future research include autophagy, GM interactions, implications for immunotherapy, exosome functions, epithelial-mesenchymal transition, and γ-glutamyl transpeptidase. The findings underscore that HP is a major risk factor for GC through mechanisms involving inflammation and immunity modulation. HP eradication may prevent early GC stages and improve treatment outcomes. In conclusion, this study provides valuable insights into the global landscape of HP/GC research suggesting potential directions for future investigations to address gaps in knowledge of their interplay.The review by Yarahmadi and Afkhami highlights the significant link between GM and the development of GI cancers, which account for a third of new cancer cases worldwide. The authors discuss how perturbations in the GI microbiota may influence cancer progression, with some bacteria being cancer-promoting and others being protective. Recent studies suggest that alterations in GM composition are associated with several GI malignancies, including colorectal, gastric, liver and esophageal cancers. The review highlights the relevance of understanding these microbial communities and their interactions with the host immunity as potential avenues for cancer prevention and treatment strategies. The authors explore how GM can affect the efficacy of cancer therapies such as chemotherapy, immunotherapy, and radiotherapy. They report that dysbiosis can lead to inflammatory responses that exacerbate cancer progression and specific bacteria, such as Fusobacterium nucleatum (F. nucleatum), have been implicated in chemoresistance in CRC. Additionally, the authors discuss emerging research on non-bacterial components of the microbiome, including viruses and fungi, which also play a role in GI cancers. For example, certain viral infections have been associated with an increased cancer risk. In conclusion, this comprehensive analysis underscores the dual GM role in both facilitating and inhibiting GI carcinogenesis, while suggesting that modulation of these microbial communities may improve therapeutic outcomes for patients with GI cancers.In their mini-review, Kumar et al. explore the relationship between GM, its secondary metabolites, and the regulation of the Wnt/β-catenin signaling pathway in the context of IBD and CRC. GI cancers represent a significant public health burden, with rising incidences associated with GM dysbiosis. The authors discuss how secondary metabolites produced by gut microbes, such as shortchain fatty acids (SCFAs) and bile acids, play a critical role in maintaining intestinal homeostasis and regulating inflammation-driven tumorigenesis. Dysbiosis can lead to altered levels of these metabolites, resulting in immune cells' activation that contributes to chronic inflammation and increased cancer risk. The review emphasizes the relevance of the Wnt/β-catenin pathway in CRC progression; in detail its dual role in modulating inflammation and promoting cell proliferation. It highlights that microbial metabolites such as butyrate inhibit this pathway, suggesting potential therapeutic avenues for treating CRC through dietary or probiotic interventions. Additionally, the authors discuss how bile acids interact with nuclear receptors such as the farnesoid X receptor to influence both bile metabolism and the Wnt signaling pathway. This interplay provides opportunities for novel therapeutic strategies targeting these mechanisms to attenuate IBD-related inflammation and CRC development. In conclusion, understanding the interactions between gut-derived metabolites and Wnt signaling may provide new treatments approaches for GI cancers while minimizing the side effects associated with conventional therapies. The review calls for further research into these relationships in order to develop effective combinatorial therapies aimed at improving treatment outcomes for patients with IBD and CRC.The research article by Kaźmierczak-Siedlecka et al. investigates the gut metabolome in patients with gastric cancer (GC) (n=4) and CRC (n=8) prior to initiation of anticancer treatments. The study aims to explore potential differences in metabolite profiles that could serve as biomarkers for these cancers. Stool samples were collected from 12 patients, and untargeted metabolomics was performed using mass spectrometry to analyze a wide range of metabolites. The results revealed distinct metabolic profiles, with higher levels of certain metabolites found predominantly in CRC patients compared to those with GC. Notably, metabolites such as deoxyguanosine, uridine, L-phenylalanine, and 3-indoleacetic acid were significantly elevated in CRC patients. The analysis revealed a more homogeneous metabolic profile among GC patients compared to the diverse profiles observed in CRC patients. This suggests that tumor localization may influence the GM activity and so its metabolites' production. The authors acknowledge the limitations due to the small sample size but emphasize that these preliminary findings pave the way for further research into untargeted metabolomics as a non-invasive tool for early detection and monitoring of GI cancers. Future studies are planned to assess the impact of anti-cancer treatments on these metabolic profiles. In conclusion, this study highlights the potential role of gut-derived metabolites as biomarkers for discriminating between GC and CRC, while highlighting the need for larger studies to validate these findings.The review by Duda-Madej et al. explores the potential links between Crohn's disease (CD), a chronic inflammatory bowel condition, and Alzheimer's disease (AD), a common neurodegenerative disorder. Both diseases are characterized by complex pathomechanisms involving genetic, environmental, immunological, and microbiological factors. Recent evidence suggests that chronic inflammation in conditions such as CD may increase the risk of AD developing. The authors highlight the gut-brain axis as a critical pathway linking these two diseases, where GM influences neuroinflammatory processes and amyloid aggregation associated with AD. Specifically, they discuss how GM dysbiosis can lead to increased permeability of the intestinal barrier, allowing proinflammatory substances to enter the systemic circulation and potentially reach the brain. The review emphasizes the role of amyloid proteins produced by both human cells and gut bacteria, especially bacterial amyloid peptides (curli fimbriae) from certain bacteria that mimic human amyloids. These bacterial amyloids may contribute to neuroinflammation and amyloid-beta aggregation in AD. Furthermore, the authors note that alterations in the GM composition may affect immune responses and metabolic processes associated with both CD and AD. They call for further research into microbial metabolites as potential therapeutic targets for the treatment of both diseases. In conclusion, this review suggests a significant relationship between CD and AD through shared inflammatory pathways and microbial influences. Understanding these links may lead to novel strategies for the prevention and treatment of neurodegenerative diseases rooted in GI health.In a systematic review by Moreira et al. the therapeutic potential of GM modulation by prebiotics, probiotics, and synbiotics in patients with CRC is discussed. The review follows PRISMA guidelines and includes 24 randomized controlled trials (RCTs) assessing the effects of these supplements on CRC treatment outcomes, focusing on surgical recovery, chemotherapy, and radiotherapy side effects. The authors found that supplementation significantly improved surgical outcomes by decreasing postoperative complications, such as infections and GI symptoms like diarrhea. The results showed that patients who received probiotics or synbiotics had a faster return to normal gut function and shorter hospital stays than control groups. In detail, specific strains such as Lactobacillus rhamnosus and Bifidobacterium lactis were often associated with positive outcomes. However, the evidence regarding the optimal formulations, such as strain combinations, dosages, and administration duration, remains limited due to high heterogeneity between trials. In addition, the review highlights that while some trials reported benefits of probiotic supplementation during chemotherapy or radiotherapy, others showed no significant improvements. The authors emphasize the need for more RCTs with larger sample sizes and standardized protocols to further clarify the effectiveness of these interventions. In conclusion, this systematic review suggests that pre-, pro-, and synbiotic supplementation may offer beneficial effects for CRC patients undergoing treatment by improving recovery and alleviating treatment-related side effects. Future research should focus on optimizing these interventions to improve clinical outcomes in CRC management.The research article by Lin et al. investigates the potential association between IBD and diabetic retinopathy (DR) using Mendelian randomization (MR) and mediation analysis. The study uses genome-wide association study (GWAS) data to explore causal relationships, focusing on IBD subtypes, ulcerative colitis (UC) and CD, and their association with DR. The results indicate a significant negative correlation between UC and DR risk, suggesting that increased inflammation in IBD may affect retinal health. Conversely, the authors suggest that DR may reduce the CD incidence. Mediation analysis identified circulating inflammatory proteins, in particular fibroblast growth factor 21 (FGF21), phosphatidylcholine, and triglycerides, as mediators in these relationships. Elevated FGF21 levels are associated with both microvascular complications in diabetes and intestinal inflammation, highlighting its potential role as a biomarker for DR. The authors emphasize the relevance of understanding the gut-retina axis, noting that dysbiosis in DR may affect systemic inflammation and lipid metabolism, influencing both conditions. They acknowledge limitations such as the focus on participants of European ancestry in the GWAS data, which may affect generalizability. In conclusion, this research provides insights into common pathways between IBD and DR, suggesting that therapeutic strategies targeting these pathways may improve outcomes for patients with both conditions. Further studies are warranted to explore these relationships more comprehensively in diverse populations.Mares et al. investigate the relationship between SIBO and constipation in pediatric patients. SIBO is characterized by an abnormal increase in bacteria in the small intestine, leading to symptoms ranging from mild GI discomfort to more serious problems such as malabsorption. The authors conducted a thorough literature search and included 79 studies that investigated the prevalence, diagnosis, and treatment of SIBO in children. They highlighted the challenges of diagnosing SIBO due to variations in methodology and lack of standardized criteria, with particular emphasis on breath tests using glucose or lactulose as substrates. The findings suggest that SIBO is common in children with functional GI disorders, although rates vary widely depending on study design. The review notes a association between during breath and although results are between strategies for SIBO include dietary and probiotics, but research into pediatric remains The authors emphasize the need for studies with larger sample sizes to and effective treatment protocols for children. In conclusion, although is evidence linking SIBO to constipation in further research is to clarify these and improve clinical management strategies. The article calls for future research to focus on standardized and to explore dietary interventions or probiotic therapies as potential treatments for pediatric their original et al. investigated the potential causal relationship between GM and diabetic using The study aimed to clarify how GM changes may influence the development and from GWAS were focusing on for IBD and the for The authors various including to causal relationships while assessing and The results showed significant between specific GM and Elevated levels of the and were associated with an increased risk, and showed effects. analysis revealed that elevated levels of and order may also contribute to an increased risk of The study highlights the of understanding the axis in relation to metabolic diseases such as It suggests that metabolites could serve as non-invasive or therapeutic targets for early In conclusion, this research provides valuable insights into the complex interactions between GM and and the that these are Further investigations are to the mechanisms and to explore potential clinical in the treatment of by GM article by et al. the association between GM and and data from the authors a to investigate these The study identified several bacterial associated with such as and which were found to have effects the other certain including were associated with an increased risk. was identified as a factor for while and a role in Conversely, genera such as and were associated with an elevated risk for the of these showing no significant or heterogeneity between the in the analysis. The analysis showed no significant causal relationships from disease to The authors suggest a potential causal relationship between specific gut microbial and disease, which may provide new opportunities and focus on GM modulation. However, they acknowledge limitations related to sample diversity and the of during their a call for further research to validate these findings in diverse study by et al. the effectiveness in in CRC patients with The analysis data from two clinical trials involving patients, who were randomized to probiotics or a during their chemotherapy The results show that while the rates of not significantly between showed that patients with who received probiotics had a significantly lower of and no cases of compared to those who received was also associated with of although this was not The study highlights the potential benefits for CRC patients with undergoing treatment with the and suggests that maintaining a healthy GM could to reduce GI associated with these the authors acknowledge limitations such as the of and the lack of human trials. They call for further research into probiotic strategies and the mechanisms the observed effects to treatment outcomes for CRC patients side effects. the study to a critical for future regarding GM modulation in cancer their original et al. investigated the role of in regulating GM during the development of metabolic dysfunction-associated fatty liver disease (MAFLD) and its progression to the study investigated how affects the GM composition are a The authors observed significant changes in microbial with an increased of beneficial such as Lactobacillus in compared to Additionally, the study found that a these microbial changes and specific bacterial associated with metabolic pathways relevant to liver health were and were associated with effects liver disease, while certain other were associated with an increased disease risk. The results suggest that plays a critical role in the GM influencing metabolic processes associated with liver highlighting the interactions between dietary and GM, this research avenues for potential therapeutic strategies targeting to gut and the progression of liver In conclusion, the study highlights the relevance of understanding how affects GM and progression to and emphasizes future research directions focusing on human studies to further explore these relationships for therapeutic original by et al. investigates the GM profiles in patients who from They to how changes in gut may contribute to GI symptoms observed in these patients. samples were collected from including with and healthy The authors differences in GM composition between the groups. The results showed that the constipation group had microbial diversity compared to patients and healthy the Enterococcus and were in patients, while beneficial such as Bifidobacterium and were The analysis that certain potentially bacteria may exacerbate inflammation and contribute to Additionally, pathways involved in metabolism and were in patients, suggesting a metabolic associated with their The study highlights a potential link between GM composition and inflammatory responses that may influence gut In conclusion, this research provides insights into how GM changes may influence constipation in patients. It highlights the need for further into specific bacterial and their role in GI health to develop therapeutic such as microbiota for the management of constipation associated with et al. investigated the causal relationship between GM and intestinal diverticular disease using a The study from a genome-wide association study involving participants to assess the GM on diverticular disease, including cases and over controls from the GWAS The analysis revealed significant between specific microbial and the risk of intestinal diverticular In detail, increased levels of and were associated with a higher risk of the Conversely, and showed effects. In addition, analysis not significant causal relationships from diverticular disease to The findings underscore that variations in GM composition may influence the and progression of diverticular This research highlights the of understanding how GM changes may contribute to GI such as It suggests potential avenues for treatment strategies targeting specific microbial to prevent or diverticular In conclusion, this study provides insights into the relationship between GM and diverticular disease, while highlighting the need for further research in diverse to validate these findings and more explore the original research article by et al. investigates the of nucleatum and its association with CRC in patients in The study included patients with CRC, from were including normal and normal the authors nucleatum with other bacteria such as Escherichia and The results showed a significantly higher nucleatum in compared to and with detection rates of and The of nucleatum was significantly higher in in the and was associated with larger tumor size and higher of Additionally, although no significant were found between nucleatum and various clinical such as or the study highlights its potential as a for CRC due to its association with tumor In conclusion, this study underscores the role of nucleatum in the CRC pathogenesis in patients and suggests that it may serve as a valuable biomarker for CRC further into its mechanisms and implications for cancer of and original research highlights the significant role of the GM in various health in relation to GI and metabolic diseases. the between GM and conditions such as CRC, diabetic diverticular disease, and complications from provide evidence that microbial composition can influence disease progression, and treatment outcomes. For example, the systematic review of pre-, synbiotic supplementation suggests that these interventions may improve surgical outcomes and reduce side effects in CRC patients. research into nucleatum its in CRC and its potential as a for this Furthermore, studies using causal relationships between GM changes and various diseases, the that specific microbial may contribute to or diseases such as and diverticular these findings underscore the relevance of understanding the of the gut microbiome and its interactions with host They suggest that targeting GM profiles through dietary or probiotic therapies may offer avenues for prevention and management strategies in various health This body of evidence highlights the need for research into the complex interplay between GM, inflammation, and disease in order to develop effective therapeutic approaches aimed at microbial balance for improved health outcomes. In potential such as and play a critical role in the GM composition and A more understanding of how these interact with microbial communities can their impact on health outcomes and disease This 11 original in and review article in The highlight the relationships between changes in the gut microbiome and several gastrointestinal disorders, including colorectal cancer (CRC), inflammatory bowel disease (IBD), diverticular disease, small intestinal bacterial overgrowth (SIBO), metabolic dysfunction-associated fatty liver disease and These changes can also associated with disease and other