Editorial

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Open AccessEditorial

Special Issue: The Role of Gut Microbiota in Gastrointestinal Cancers—From Pathogenesis to Therapeutic Perspectives

by Ryota Niikura

Biomedicines 2023, 11(11), 2950; https://doi.org/10.3390/biomedicines11112950 - 01 Nov 2023

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Associations between the gut microbiota and gastrointestinal carcinogenesis have been intensively studied [...] Full article

(This article belongs to the Special Issue The Role of Gut Microbiota in Gastrointestinal Cancers: From Pathogenesis to Therapeutic Perspectives)

Research

Jump to: Editorial, Review

15 pages, 4455 KiB

Open AccessArticle

Exploring Gut Microenvironment in Colorectal Patient with Dual-Omics Platform: A Comparison with Adenomatous Polyp or Occult Blood

by Po-Li Wei, Ming-Shun Wu, Chun-Kai Huang, Yi-Hsien Ho, Ching-Sheng Hung, Ying-Chin Lin, Mei-Fen Tsao and Jung-Chun Lin

Biomedicines 2022, 10(7), 1741; https://doi.org/10.3390/biomedicines10071741 - 19 Jul 2022

Cited by 4 | Viewed by 1959

Abstract

The gut mucosa is actively absorptive and functions as the physical barrier to separate the gut ecosystem from host. Gut microbiota-utilized or food-derived metabolites are closely relevant to the homeostasis of the gut epithelial cells. Recent studies widely suggested the carcinogenic impact of [...] Read more.

The gut mucosa is actively absorptive and functions as the physical barrier to separate the gut ecosystem from host. Gut microbiota-utilized or food-derived metabolites are closely relevant to the homeostasis of the gut epithelial cells. Recent studies widely suggested the carcinogenic impact of gut dysbiosis or altered metabolites on the development of colorectal cancer (CRC). In this study, liquid chromatography coupled-mass spectrometry and long-read sequencing was applied to identify gut metabolites and microbiomes with statistically discriminative abundance in CRC patients (n = 20) as compared to those of a healthy group (n = 60) ofenrolled participants diagnosed with adenomatous polyp (n = 67) or occult blood (n = 40). In total, alteration in the relative abundance of 90 operational taxonomic units (OTUs) and 45 metabolites were identified between recruited CRC patients and healthy participants. Among the candidates, the gradual increases in nine OTUs or eight metabolites were identified in healthy participants, patients diagnosed with occult blood and adenomatous polyp, and CRC patients. The random forest regression model constructed with five OTUs or four metabolites achieved a distinct classification potential to differentially discriminate the presence of CRC (area under the ROC curve (AUC) = 0.998 or 0.975) from the diagnosis of adenomatous polyp (AUC = 0.831 or 0.777), respectively. These results provide the validity of CRC-associated markers, including microbial communities and metabolomic profiles across healthy and related populations toward the early screening or diagnosis of CRC. Full article

(This article belongs to the Special Issue The Role of Gut Microbiota in Gastrointestinal Cancers: From Pathogenesis to Therapeutic Perspectives)

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11 pages, 4907 KiB

Open AccessArticle

Clinicopathological Features of Gastric Cancer with Autoimmune Gastritis

by Junya Arai, Ryota Niikura, Yoku Hayakawa, Nobumi Suzuki, Yoshihiro Hirata, Tetsuo Ushiku and Mitsuhiro Fujishiro

Biomedicines 2022, 10(4), 884; https://doi.org/10.3390/biomedicines10040884 - 12 Apr 2022

Cited by 10 | Viewed by 2673

Abstract

Most gastric cancers develop in patients with chronic gastritis. Chronic gastritis can be classified into two major subtypes: Helicobacter pylori (H. pylori)-induced gastritis and autoimmune gastritis (AIG). Whereas H. pylori-related gastric cancers are more common and have been extensively investigated, [...] Read more.

Most gastric cancers develop in patients with chronic gastritis. Chronic gastritis can be classified into two major subtypes: Helicobacter pylori (H. pylori)-induced gastritis and autoimmune gastritis (AIG). Whereas H. pylori-related gastric cancers are more common and have been extensively investigated, the clinicopathological features of gastric cancer with autoimmune gastritis are unclear. Patients diagnosed with gastric cancer and hospitalized in the University Tokyo Hospital from 1998 to 2017 were enrolled. Diagnosis of autoimmune gastritis was based on positivity for serum anti-parietal cell antibody (APCA). We evaluated mucin expression and immune cell infiltration by immunohistochemical staining for MUC5AC, MUC6, PD-L1, CD3, CD11, Foxp3, and PD1. We also examined the presence of bacterial taxa that are reportedly enriched in AIG. Survival analyses of recurrence and 5-year mortality were also performed. In total, 261 patients (76 APCA-positive and 185 APCA-negative) were analyzed. Immunohistochemical staining in the matched cohort showed that AIG-related gastric cancer had higher MUC5AC expression (p = 0.0007) and MUC6 expression (p = 0.0007). Greater infiltration of CD3-positive (p = 0.001), Foxp3-positive (p < 0.001), and PD1-positive cells (p = 0.001); lesser infiltration of CD11b-positive (p = 0.005) cells; and a higher prevalence of Bacillus cereus (p = 0.006) were found in AIG-related gastric cancer patients. The cumulative incidences of gastric cancer recurrence were 2.99% at 2 years, 15.68% at 6 years, and 18.81% at 10 years in APCA-positive patients; they were 12.79% at 2 years, 21.35% at 6 years, and 31.85% at 10 years in APCA-negative patients. The cumulative incidences of mortality were 0% at 3 years and 0% at 5 years in APCA-positive patients; they were 1.52% at 3 years and 2.56% at 5 years in APCA-negative patients. We identified molecular differences between AIG and non-AIG gastric cancer. Differences in T-cell populations and the gastric microbiota may contribute to the pathogenesis of gastric cancers and potentially affect the response to immunotherapy. Full article

(This article belongs to the Special Issue The Role of Gut Microbiota in Gastrointestinal Cancers: From Pathogenesis to Therapeutic Perspectives)

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11 pages, 1598 KiB

Open AccessArticle

Different Metabolites of the Gastric Mucosa between Patients with Current Helicobacter pylori Infection, Past Infection, and No Infection History

by Su-Young Son, Choong-Hwan Lee and Sun-Young Lee

Biomedicines 2022, 10(3), 556; https://doi.org/10.3390/biomedicines10030556 - 26 Feb 2022

Cited by 2 | Viewed by 1661

Abstract

Helicobacter pylori (H. pylori) alters metabolism during the gastric carcinogenesis process. This study aimed to determine the metabolites in the gastric mucosa according to the status of the H. pylori infection. Patients who visited the outpatient clinic for a gastroscopy and [...] Read more.

Helicobacter pylori (H. pylori) alters metabolism during the gastric carcinogenesis process. This study aimed to determine the metabolites in the gastric mucosa according to the status of the H. pylori infection. Patients who visited the outpatient clinic for a gastroscopy and H. pylori tests were included. Gas chromatography–time-of-flight mass spectrometry (GC-TOF-MS) analysis was performed using gastric biopsied specimens from the corpus. Twenty-eight discriminative metabolites were found in the gastric mucosa of 10 patients with current H. pylori infection, in 15 with past infection, and in five with no infection history. The relative abundances (RAs) of amino acids and sugars/sugar alcohols were higher in patients with no infection history than in patients with current or past infection. The current infection group showed higher RAs of organic acids and lower RAs of fatty acids and lipids compared with the other groups. The RA of inosine was highest in the past infection group. Based on GC-TOF-MS analysis findings, metabolites differed not only between the infected and non-infected patients, but also between those with and without infection history. Amino acid and sugars/sugar alcohol metabolites decreased in patients with current or past infection, whereas fatty acid and lipid metabolites decreased only during current infection. Full article

(This article belongs to the Special Issue The Role of Gut Microbiota in Gastrointestinal Cancers: From Pathogenesis to Therapeutic Perspectives)

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20 pages, 2963 KiB

Open AccessArticle

The Effects of HP0044 and HP1275 Knockout Mutations on the Structure and Function of Lipopolysaccharide in Helicobacter pylori Strain 26695

by Ai-Ning Liu, Kai-Wen Teng, Yongyu Chew, Po-Chuan Wang, Tram Thi Hong Nguyen and Mou-Chieh Kao

Biomedicines 2022, 10(1), 145; https://doi.org/10.3390/biomedicines10010145 - 10 Jan 2022

Cited by 5 | Viewed by 2054

Abstract

Helicobacter pylori infection is associated with several gastric diseases, including gastritis, peptic ulcer, gastric adenocarcinoma and mucosa-associated lymphatic tissue (MALT) lymphoma. Due to the prevalence and severeness of H. pylori infection, a thorough understanding of this pathogen is necessary. Lipopolysaccharide, one of the [...] Read more.

Helicobacter pylori infection is associated with several gastric diseases, including gastritis, peptic ulcer, gastric adenocarcinoma and mucosa-associated lymphatic tissue (MALT) lymphoma. Due to the prevalence and severeness of H. pylori infection, a thorough understanding of this pathogen is necessary. Lipopolysaccharide, one of the major virulence factors of H. pylori, can exert immunomodulating and immunostimulating functions on the host. In this study, the HP0044 and HP1275 genes were under investigation. These two genes potentially encode GDP-D-mannose dehydratase (GMD) and phosphomannomutase (PMM)/phosphoglucomutase (PGM), respectively, and are involved in the biosynthesis of fucose. HP0044 and HP1275 knockout mutants were generated; both mutants displayed a truncated LPS, suggesting that the encoded enzymes are not only involved in fucose production but are also important for LPS construction. In addition, these two gene knockout mutants exhibited retarded growth, increased surface hydrophobicity and autoaggregation as well as being more sensitive to the detergent SDS and the antibiotic novobiocin. Furthermore, the LPS-defective mutants also had significantly reduced bacterial infection, adhesion and internalization in the in vitro cell line model. Moreover, disruptions of the HP0044 and HP1275 genes in H. pylori altered protein sorting into outer membrane vesicles. The critical roles of HP0044 and HP1275 in LPS biosynthesis, bacterial fitness and pathogenesis make them attractive candidates for drug inventions against H. pylori infection. Full article

(This article belongs to the Special Issue The Role of Gut Microbiota in Gastrointestinal Cancers: From Pathogenesis to Therapeutic Perspectives)

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Review

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Open AccessReview

Bacterial Translocation in Gastrointestinal Cancers and Cancer Treatment

by Keita Kouzu, Hironori Tsujimoto, Yoji Kishi, Hideki Ueno and Nariyoshi Shinomiya

Biomedicines 2022, 10(2), 380; https://doi.org/10.3390/biomedicines10020380 - 04 Feb 2022

Cited by 15 | Viewed by 2977

Abstract

In recent years, there has been increasing evidence that gut microbiota is associated with the onset and exacerbation of various diseases, such as gastrointestinal cancer. For instance, it is well known that local inflammation of the intestinal tract in colorectal cancer that is [...] Read more.

In recent years, there has been increasing evidence that gut microbiota is associated with the onset and exacerbation of various diseases, such as gastrointestinal cancer. For instance, it is well known that local inflammation of the intestinal tract in colorectal cancer that is caused by the increased number of Fusobacterium, due to changes in the intestinal bacterial flora, is involved in carcinogenesis. In contrast, gut bacteria or their products, pathogen-associated molecular patterns, not only cause intestinal inflammation but also invade the bloodstream through dysbiosis and gut barrier dysfunction, thereby leading to systemic inflammation, namely bacterial translocation. The involvement of bacterial translocation in the carcinogenesis of gastrointestinal cancers and their prognosis is increasingly being recognized. The Toll-like receptor signaling pathways plays an important role in the carcinogenesis of such cancers. In addition, bacterial translocation influences the treatment of cancers such as surgery and chemotherapy. In this review, we outline the concept of bacterial translocation, summarize the current knowledge on the relationship between gut bacteria and gastrointestinal cancer, and provide future perspectives of this field. Full article

(This article belongs to the Special Issue The Role of Gut Microbiota in Gastrointestinal Cancers: From Pathogenesis to Therapeutic Perspectives)

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Graphical abstract

20 pages, 670 KiB

Open AccessReview

The Association of Gut Microbiota and Complications in Gastrointestinal-Cancer Therapies

by Kevin M. Tourelle, Sebastien Boutin, Markus A. Weigand and Felix C. F. Schmitt

Biomedicines 2021, 9(10), 1305; https://doi.org/10.3390/biomedicines9101305 - 24 Sep 2021

Cited by 4 | Viewed by 2789

Abstract

The therapy of gastrointestinal carcinomas includes surgery, chemo- or immunotherapy, and radiation with diverse complications such as surgical-site infection and enteritis. In recent years, the microbiome’s influence on different diseases and complications has been studied in more detail using methods such as next-generation [...] Read more.

The therapy of gastrointestinal carcinomas includes surgery, chemo- or immunotherapy, and radiation with diverse complications such as surgical-site infection and enteritis. In recent years, the microbiome’s influence on different diseases and complications has been studied in more detail using methods such as next-generation sequencing. Due to the relatively simple collectivisation, the gut microbiome is the best-studied so far. While certain bacteria are sometimes associated with one particular complication, it is often just the loss of alpha diversity linked together. Among others, a strong influence of Fusobacterium nucleatum on the effectiveness of chemotherapies is demonstrated. External factors such as diet or specific medications can also predispose to dysbiosis and lead to complications. In addition, there are attempts to treat developed dysbiosis, such as faecal microbiota transplant or probiotics. In the future, the underlying microbiome should be investigated in more detail for a better understanding of the precipitating factors of a complication with specific therapeutic options. Full article

(This article belongs to the Special Issue The Role of Gut Microbiota in Gastrointestinal Cancers: From Pathogenesis to Therapeutic Perspectives)

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13 pages, 884 KiB

Open AccessReview

Drug–Microbiota Interaction in Colon Cancer Therapy: Impact of Antibiotics

by Ali Mohamed, Harry Menon, Marina Chulkina, Nelson S. Yee and Irina V. Pinchuk

Biomedicines 2021, 9(3), 259; https://doi.org/10.3390/biomedicines9030259 - 05 Mar 2021

Cited by 14 | Viewed by 3143

Abstract

Colon adenocarcinoma is one of the most common malignancies, and it is highly lethal. Chemotherapy plays an important role in the treatment of colon cancer at various stages of the disease. The gut microbiome has emerged as a key player in colon cancer [...] Read more.

Colon adenocarcinoma is one of the most common malignancies, and it is highly lethal. Chemotherapy plays an important role in the treatment of colon cancer at various stages of the disease. The gut microbiome has emerged as a key player in colon cancer development and progression, and it can also alter the therapeutic agent’s efficacy and toxicities. Antibiotics can directly and/or indirectly affect the balance of the gut microbiome and, therefore, the clinical outcomes. In this article, we provided an overview of the composition of the gut microbiome under homeostasis and the mechanistic links between gut microbiota and colon cancer. The relationship between the use of oral antibiotics and colon cancer, as well as the impact of the gut microbiome on the efficacy and toxicities of chemotherapy in colon cancer, are discussed. Potential interventions to modulate microbiota and improve chemotherapy outcomes are discussed. Further studies are indicated to address these key gaps in the field and provide a scientific basis for the design of novel microbiota-based approaches for prevention/use as adjuvant therapeutics for patients with colon cancer. Full article

(This article belongs to the Special Issue The Role of Gut Microbiota in Gastrointestinal Cancers: From Pathogenesis to Therapeutic Perspectives)

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