Malnutrition Accelerates Colorectal Cancer Progression through Macrophage Activated by B Cells Immune via Gut Microbiota

Abstract Background: Malnutrition threatened the clinical outcomes of colorectal cancer (CRC) by reducing patients’ responses to anti-cancer treatments and ultimately shortening thesurvival time. Recently malnutrition has been confirmed to play an important role in CRC progress via gut microbiota. However, roles of gut microbiota in the immunopathogenesis of malnutrition and its underlying mechanisms remain inconclusive. Methods: Patient-Generated Subjective Global Assessment (PG-SGA) was performed to determine the nutrition status in colon cancer patients. 16srRNA sequencing was prepared to explore the dramatic variation of the fecal microbiota among patients with different nutrition status. Fecal microbiota transplantation was used to transplant into C57BL/6J mice model and DSS/AOM mice model. Immunohistochemistry and immunofluorescence were applied to test the CD makers. Fluorescence-activated cell sorting was also prepared to explore the B cells and macrophage from serum and tissues. Enzyme-linked immunosorbent assay and qPCR were used to determine the expression level of cytokines.Results: In this work, we found the specific microbiota species including Atopobium.vaginae, Selenomonas.sputigena and Faecalibacterium.prausnitzii, which may be considered as the diagnostic biomarkers to help improve poor prognosis in CRC. These microbiota were found to be protumorigenic and adversely affect the nutritional status and overall survival of the animal models. More importantly, our evidence suggesting that these fecal microbiota recruited B cells and macrophage to activate the specific tumor immune in CRC. Depletion of B cells significantly suppressed fecal microbiota induced-M2b polarization, as well as the protumorigenic activity of tumor-associated macrophages in vivo.Conclusion: gut microbiome in CRC under malnutrition status could upregulate the activity of B cells and protumorigenic macrophage in CRC. Gut microbiome intervention could be a feasible approach to malnutrition-related CRC treatment.

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Interplay between the Gut Microbiota and Inflammatory Mediators in the Development of Colorectal Cancer

Cancers ◽

10.3390/cancers13040734 ◽

2021 ◽

Vol 13 (4) ◽

pp. 734

Author(s):

Gwangbeom Heo ◽

Yunna Lee ◽

Eunok Im

Keyword(s):

Colorectal Cancer ◽

Gut Microbiota ◽

Inflammatory Mediators ◽

Tumor Metastasis ◽

Intestinal Tract ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Therapeutic Interventions ◽

Potential Therapeutic Target ◽

Necrosis Factor

Inflammatory mediators modulate inflammatory pathways during the development of colorectal cancer. Inflammatory mediators secreted by both immune and tumor cells can influence carcinogenesis, progression, and tumor metastasis. The gut microbiota, which colonize the entire intestinal tract, especially the colon, are closely linked to colorectal cancer through an association with inflammatory mediators such as tumor necrosis factor, nuclear factor kappa B, interleukins, and interferons. This association may be a potential therapeutic target, since therapeutic interventions targeting the gut microbiota have been actively investigated in both the laboratory and in clinics and include fecal microbiota transplantation and probiotics.

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A theoretical model of temperate phages as mediators of gut microbiome dysbiosis

F1000Research ◽

10.12688/f1000research.18480.1 ◽

2019 ◽

Vol 8 ◽

pp. 997 ◽

Cited By ~ 1

Author(s):

Derek M. Lin ◽

Henry C. Lin

Keyword(s):

Colorectal Cancer ◽

Inflammatory Bowel Disease ◽

Bacterial Community ◽

Gut Microbiome ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Functional Changes ◽

Inflammatory Bowel ◽

Insight Into

Bacteriophages are the most prominent members of the gut microbiome, outnumbering their bacterial hosts by a factor of 10. Phages are bacteria-specific viruses that are gaining attention as highly influential regulators of the gut bacterial community. Dysregulation of the gut bacterial community contributes to dysbiosis, a microbiome disorder characterized by compositional and functional changes that contribute to disease. A role for phages in gut microbiome dysbiosis is emerging with evidence that the gut phage community is altered in dysbiosis-associated disorders such as colorectal cancer and inflammatory bowel disease. Several recent studies have linked successful fecal microbiota transplantation to uptake of the donor’s gut phage community, offering some insight into why some recipients respond to treatment whereas others do not. Here, we review the literature supporting a role for phages in mediating the gut bacterial community, giving special attention to Western diet dysbiosis as a case study to demonstrate a theoretical phage-based mechanism for the establishment and maintenance of dysbiosis.

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The Role of Gut Microbiota in Lung Cancer: From Carcinogenesis to Immunotherapy

Frontiers in Oncology ◽

10.3389/fonc.2021.720842 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xiangjun Liu ◽

Ye Cheng ◽

Dan Zang ◽

Min Zhang ◽

Xiuhua Li ◽

...

Keyword(s):

Lung Cancer ◽

Gut Microbiota ◽

Gut Microbiome ◽

Fecal Microbiota Transplantation ◽

Checkpoint Inhibitors ◽

Fecal Microbiota ◽

Immune Homeostasis ◽

Gut Dysbiosis ◽

Underlying Mechanisms ◽

And Function

The influence of microbiota on host health and disease has attracted adequate attention, and gut microbiota components and microbiota-derived metabolites affect host immune homeostasis locally and systematically. Some studies have found that gut dysbiosis, disturbance of the structure and function of the gut microbiome, disrupts pulmonary immune homeostasis, thus leading to increased disease susceptibility; the gut-lung axis is the primary cross-talk for this communication. Gut dysbiosis is involved in carcinogenesis and the progression of lung cancer through genotoxicity, systemic inflammation, and defective immunosurveillance. In addition, the gut microbiome harbors the potential to be a novel biomarker for predicting sensitivity and adverse reactions to immunotherapy in patients with lung cancer. Probiotics and fecal microbiota transplantation (FMT) can enhance the efficacy and depress the toxicity of immune checkpoint inhibitors by regulating the gut microbiota. Although current studies have found that gut microbiota closely participates in the development and immunotherapy of lung cancer, the mechanisms require further investigation. Therefore, this review aims to discuss the underlying mechanisms of gut microbiota influencing carcinogenesis and immunotherapy in lung cancer and to provide new strategies for governing gut microbiota to enhance the prevention and treatment of lung cancer.

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Gut Microbiota Manipulation as a Tool for Colorectal Cancer Management: Recent Advances in Its Use for Therapeutic Purposes

International Journal of Molecular Sciences ◽

10.3390/ijms21155389 ◽

2020 ◽

Vol 21 (15) ◽

pp. 5389

Author(s):

Federica Perillo ◽

Chiara Amoroso ◽

Francesco Strati ◽

Maria Rita Giuffrè ◽

Angélica Díaz-Basabe ◽

...

Keyword(s):

Colorectal Cancer ◽

Gut Microbiota ◽

Targeted Therapies ◽

Inflammatory Responses ◽

Fecal Microbiota Transplantation ◽

Large Body ◽

Cancer Recurrence ◽

Fecal Microbiota ◽

Cancer Management ◽

Host Microbe Interactions

Colorectal cancer (CRC) is a multifaceted disease influenced by both environmental and genetic factors. A large body of literature has demonstrated the role of gut microbes in promoting inflammatory responses, creating a suitable microenvironment for the development of skewed interactions between the host and the gut microbiota and cancer initiation. Even if surgery is the primary therapeutic strategy, patients with advanced disease or cancer recurrence after surgery remain difficult to cure. Therefore, the gut microbiota has been proposed as a novel therapeutic target in light of recent promising data in which it seems to modulate the response to cancer immunotherapy. The use of microbe-targeted therapies, including antibiotics, prebiotics, live biotherapeutics, and fecal microbiota transplantation, is therefore considered to support current therapies in CRC management. In this review, we will discuss the importance of host−microbe interactions in CRC and how promoting homeostatic immune responses through microbe-targeted therapies may be useful in preventing/treating CRC development.

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Potential Role of the Gut Microbiome In Colorectal Cancer Progression

Frontiers in Immunology ◽

10.3389/fimmu.2021.807648 ◽

2022 ◽

Vol 12 ◽

Author(s):

Jaeho Kim ◽

Heung Kyu Lee

Keyword(s):

Colorectal Cancer ◽

Gut Microbiota ◽

Cancer Treatment ◽

Cancer Progression ◽

Gut Microbiome ◽

Intestinal Inflammation ◽

Treatment Modalities ◽

Host Immune System ◽

Anti Cancer

An increasing number of studies have revealed that the progression of colorectal cancer (CRC) is related to gut microbiome composition. Under normal conditions, the gut microbiome acts as a barrier to other pathogens or infections in the intestine and modulates inflammation by affecting the host immune system. These gut microbiota are not only related to the intestinal inflammation associated with tumorigenesis but also modulation of the anti-cancer immune response. Thus, they are associated with tumor progression and anti-cancer treatment efficacy. Studies have shown that the gut microbiota can be used as biomarkers to predict the effect of immunotherapy and improve the efficacy of immunotherapy in treating CRC through modulation. In this review, we discuss the role of the gut microbiome as revealed by recent studies of the growth and progression of CRC along with its synergistic effect with anti-cancer treatment modalities.

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The Brain-Gut-Microbiome System: Pathways and Implications for Autism Spectrum Disorder

Nutrients ◽

10.3390/nu13124497 ◽

2021 ◽

Vol 13 (12) ◽

pp. 4497

Author(s):

Michelle A. Chernikova ◽

Genesis D. Flores ◽

Emily Kilroy ◽

Jennifer S. Labus ◽

Emeran A. Mayer ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Gut Microbiota ◽

Gut Microbiome ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Preclinical Research ◽

Gastrointestinal Problems ◽

The Brain

Gastrointestinal dysfunction is one of the most prevalent physiological symptoms of autism spectrum disorder (ASD). A growing body of largely preclinical research suggests that dysbiotic gut microbiota may modulate brain function and social behavior, yet little is known about the mechanisms that underlie these relationships and how they may influence the pathogenesis or severity of ASD. While various genetic and environmental risk factors have been implicated in ASD, this review aims to provide an overview of studies elucidating the mechanisms by which gut microbiota, associated metabolites, and the brain interact to influence behavior and ASD development, in at least a subgroup of individuals with gastrointestinal problems. Specifically, we review the brain-gut-microbiome system and discuss findings from current animal and human studies as they relate to social-behavioral and neurological impairments in ASD, microbiota-targeted therapies (i.e., probiotics, fecal microbiota transplantation) in ASD, and how microbiota may influence the brain at molecular, structural, and functional levels, with a particular interest in social and emotion-related brain networks. A deeper understanding of microbiome-brain-behavior interactions has the potential to inform new therapies aimed at modulating this system and alleviating both behavioral and physiological symptomatology in individuals with ASD.

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Gastrointestinal disturbance and effect of fecal microbiota transplantation in discharged COVID-19 patients

10.21203/rs.3.rs-54135/v1 ◽

2020 ◽

Author(s):

Zhaoqun Deng ◽

Fengqiong Liu ◽

Shanliang Ye ◽

Xin Zhu ◽

Xuesong He ◽

...

Keyword(s):

B Cells ◽

Gut Microbiota ◽

Post Infection ◽

Fecal Microbiota Transplantation ◽

Gastrointestinal Symptoms ◽

Fecal Microbiota ◽

Psychological Disorder ◽

Community Diversity ◽

General Distribution ◽

Gut Dysbiosis

Abstract Background: Gastrointestinal manifestations and gut dysbiosis are prevalent after SARS-CoV2 infection.With the continuously increasing number of infected cases, more attention should be paid to this particular population in post-infection recovery.cWe aimed to investigate the potential beneficial effect of FMT on gastrointestinal symptoms, gut dysbiosis and immune status in discharged COVID-19 patients. Results: Gastrointestinal and psychological disorder (45.5%) were observed in COVID-19 patients during post-infection recovery, improvement of which were observed after FMT. Most of the lab results including blood routine and blood biochemistry, within the normal range. The general distribution of 69 different types of lymphocytes differed between before and after FMT. FMT exert significant effect on B cells which was characterized as decreased naive B cell ( P =0.012) and increased memory B cells ( P = 0.001) and non-switched B cells ( P = 0.012).The microbial community richness indicated by OTUs number, observed species and Chao1 estimators was marginally increased after FMT, whereas the community diversity estimated by the Shannon and Simpson index showed no significant changes after FMT. Gut microbiome composition of discharged COVID-19 patients differed from that of the general population at both phylum and genera level, which was characterized with a lower proportion of Firmicutes (41.0%) and Actinobacteria (4.0%), higher proportion of Bacteroidetes (42.9%) and Proteobacteriato (9.2%). FMT can partially restore the gutdysbiosis by increasing the relative abundance of Actinobacteria (15.0%) and reducing Proteobacteriato (2.8%) at the phylum level. At the genera level, Bifidobacterium and Faecalibacterium , which were dominant genera in the human gut microbiota and were beneficial for human health, had significantly increased after FMT. Conclusions: Gastrointestinal and gut dysbiosis were observed in COVID-19 patients during post-infection recovery. FMT can improve the immune functionality, restore the gut microbiota, alleviate gastrointestinal disorders, and may serve as a potential therapeutic and rehabilitative intervention for the COVID-19.

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Fecal microbiota transplant overcomes resistance to anti–PD-1 therapy in melanoma patients

Science ◽

10.1126/science.abf3363 ◽

2021 ◽

Vol 371 (6529) ◽

pp. 595-602 ◽

Cited By ~ 1

Author(s):

Diwakar Davar ◽

Amiran K. Dzutsev ◽

John A. McCulloch ◽

Richard R. Rodrigues ◽

Joe-Marc Chauvin ◽

...

Keyword(s):

Gut Microbiota ◽

T Cell Activation ◽

Gut Microbiome ◽

Cell Activation ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Advanced Melanoma ◽

Fecal Microbiota Transplant ◽

Network Analyses ◽

Clinical Benefits

Anti–programmed cell death protein 1 (PD-1) therapy provides long-term clinical benefits to patients with advanced melanoma. The composition of the gut microbiota correlates with anti–PD-1 efficacy in preclinical models and cancer patients. To investigate whether resistance to anti–PD-1 can be overcome by changing the gut microbiota, this clinical trial evaluated the safety and efficacy of responder-derived fecal microbiota transplantation (FMT) together with anti–PD-1 in patients with PD-1–refractory melanoma. This combination was well tolerated, provided clinical benefit in 6 of 15 patients, and induced rapid and durable microbiota perturbation. Responders exhibited increased abundance of taxa that were previously shown to be associated with response to anti–PD-1, increased CD8+ T cell activation, and decreased frequency of interleukin-8–expressing myeloid cells. Responders had distinct proteomic and metabolomic signatures, and transkingdom network analyses confirmed that the gut microbiome regulated these changes. Collectively, our findings show that FMT and anti–PD-1 changed the gut microbiome and reprogrammed the tumor microenvironment to overcome resistance to anti–PD-1 in a subset of PD-1 advanced melanoma.

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Fecal Microbiota Transplantation Prevents Intestinal Injury, Upregulation of Toll-Like Receptors, and 5-Fluorouracil/Oxaliplatin-Induced Toxicity in Colorectal Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms21020386 ◽

2020 ◽

Vol 21 (2) ◽

pp. 386 ◽

Cited By ~ 11

Author(s):

Ching-Wei Chang ◽

Hung-Chang Lee ◽

Li-Hui Li ◽

Jen-Shiu Chiang Chiau ◽

Tsang-En Wang ◽

...

Keyword(s):

Colorectal Cancer ◽

Gut Microbiota ◽

Fecal Microbiota Transplantation ◽

Common Adverse Effect ◽

Mucosal Injury ◽

Fecal Microbiota ◽

Intestinal Injury ◽

Toll Like Receptors ◽

Adenocarcinoma Cells ◽

Intestinal Mucositis

FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin), a 5-fluorouracil (5-FU)-based chemotherapy regimen, is one of most common therapeutic regimens for colorectal cancer. However, intestinal mucositis is a common adverse effect for which no effective preventive strategies exist. Moreover, the efficacy and the safety of fecal microbiota transplants (FMT) in cancer patients treated with anti-neoplastic agents are still scant. We investigated the effect of FMT on FOLFOX-induced mucosal injury. BALB/c mice implanted with syngeneic CT26 colorectal adenocarcinoma cells were orally administered FMT daily during and two days after five-day injection of FOLFOX regimen for seven days. Administration of FOLFOX significantly induced marked levels of diarrhea and intestinal injury. FMT reduced the severity of diarrhea and intestinal mucositis. Additionally, the number of goblet cells and zonula occludens-1 decreased, while apoptotic and NF-κB-positive cells increased following FOLFOX treatment. The expression of toll-like receptors (TLRs), MyD88, and serum IL-6 were upregulated following FOLFOX treatment. These responses were attenuated following FMT. The disrupted fecal gut microbiota composition was also restored by FMT after FOLFOX treatment. Importantly, FMT did not cause bacteremia and safely alleviated FOLFOX-induced intestinal mucositis in colorectal cancer-bearing mice. The putative mechanism may involve the gut microbiota TLR-MyD88-NF-κB signaling pathway in mice with implanted colorectal carcinoma cells.

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