Chemotherapeutic Drugs Induce Different Gut Microbiota Disorder Pattern and NOD/RIP2/NF-κB Signaling Pathway Activation That Lead to Different Degrees of Intestinal Injury

Huang, Bin; Gui, Mengxuan; Ni, Zhuona; He, Yanbin; Zhao, Jinyan; Peng, Jun; Lin, Jiumao

doi:10.1128/spectrum.01677-22

Cited by 12 publications

(4 citation statements)

References 66 publications

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“…It has previously been shown that Candidatus Saccharimonas was the most abundant genera in colitis-associated CRC, and it was also associated with other inflammatory diseases . For instance, Candidatus Saccharimonas was positively correlated with nucleotide-binding oligomerization domain (NODs)/receptor-interacting protein 2 (RIP2)/NF-κB signaling pathway in redundancy (RDA)/canonical correspondence (CCA) analyses . CUR and AC reduced Candidatus Saccharimonas abundance, indicating their beneficial effect on CRC (Figure E).…”

Section: Discussionmentioning

confidence: 81%

“…38 For instance, Candidatus Saccharimonas was positively correlated with nucleotidebinding oligomerization domain (NODs)/receptor-interacting protein 2 (RIP2)/NF-κB signaling pathway in redundancy (RDA)/canonical correspondence (CCA) analyses. 39 CUR and AC reduced Candidatus Saccharimonas abundance, indicating their beneficial effect on CRC (Figure 7E). In comparison, Bacteroides and Eubacterium nodatum group abundances were elevated in the LAC group, which might be associated with the ameliorative effect of low AC doses (Figure 7G).…”

Section: Discussionmentioning

confidence: 90%

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Amination Potentially Augments the Ameliorative Effect of Curcumin on Inhibition of the IL-6/Stat3/c-Myc Pathway and Gut Microbial Modulation in Colitis-Associated Tumorigenesis

Koh

Tsai

Lee

et al. 2022

J. Agric. Food Chem.

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Epigallocatechin gallate and tetrahydrocurcumin are aminated as colonic metabolites, preserving their bioactivities and improving their capabilities. We compared the bioactivities of unaminated (CUR) and aminated (AC) curcumin in inflammatory colitis-associated tumorigenesis. The anti-inflammatory and anticancer capabilities of CUR and AC were evaluated using RAW264.7 and HT29 cell lines, respectively. An azoxymethane/dextran sodium sulfate-induced colitis-associated carcinogenesis mouse model was used with CUR and two-dose AC interventions. AC had a greater anti-inflammatory effect but a similar anticancer effect as CUR in vitro. CUR and low-dose AC (LAC) significantly preserved colon length and reduced tumor number in vivo. Both CUR and LAC inhibited activation of the protein kinase B (AKT)/nuclear factor kappa B (NF-κB) signaling pathway, its downstream cytokines, and the interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3)/cmyelocytomatosis oncogene (c-MYC) pathway. However, only LAC significantly preserved E-cadherin, reduced N-cadherin, and facilitated beneficial gut microbial growth, including Akkermansia and Bacteroides, potentially explaining AC's better ameliorative effect at low than high doses.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 90%

Amination Potentially Augments the Ameliorative Effect of Curcumin on Inhibition of the IL-6/Stat3/c-Myc Pathway and Gut Microbial Modulation in Colitis-Associated Tumorigenesis

Koh

Tsai

Lee

et al. 2022

J. Agric. Food Chem.

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“…[ 64 ] However, the mechanisms through which 5‐FU triggers gut microbiota dysbiosis and how dysbiosis exacerbates 5‐FU‐induced intestinal mucositis required further investigation. [ 65 ] Our study showed that 5‐FU might contribute to the destruction and functional decline of intestinal epithelial cells by toxicity‐induced apoptosis and that this destruction might lead to the loss of Muc2, which is the main protein in the mucous layer, thereby preventing the establishment of a stable gut microbiota. [ 66 ] Furthermore, the deficiency of Reg3b, an antimicrobial peptide, disrupts the balance between beneficial and pathogenic bacteria.…”

Section: Discussionmentioning

confidence: 99%

L‐Glutamine Substantially Improves 5‐Fluorouracil‐Induced Intestinal Mucositis by Modulating Gut Microbiota and Maintaining the Integrity of the Gut Barrier in Mice

Kuo,

Lin,

Lin

et al. 2024

Molecular Nutrition Food Res

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ScopeThis study investigates the potential of glutamine to mitigate intestinal mucositis and dysbiosis caused by the chemotherapeutic agent 5‐fluorouracil (5‐FU).Methods and resultsOver twelve days, Institute of Cancer Research (ICR) mice are given low (0.5 mg kg−1) or high (2 mg kg−1) doses of L‐Glutamine daily, with 5‐FU (50 mg kg−1) administered between days six and nine. Mice receiving only 5‐FU exhibited weight loss, diarrhea, abnormal cell growth, and colonic inflammation, correlated with decreased mucin proteins, increased endotoxins, reduced fecal short‐chain fatty acids, and altered gut microbiota. Glutamine supplementation counteracted these effects by inhibiting the Toll‐like receptor 4/nuclear factor kappa B (TLR4/NF‐κB) pathway, modulating nuclear factor erythroid 2‐related factor 2/heme oxygenase 1 (Nrf2/HO‐1) oxidative stress proteins, and increasing mammalian target of rapamycin (mTOR) levels, thereby enhancing microbial diversity and protecting intestinal mucosa.ConclusionsThese findings underscore glutamine's potential in preventing 5‐FU‐induced mucositis by modulating gut microbiota and inflammation pathways.

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“… 228 Moreover, Streptococcus exhibited a compelling correlation with the NOD/RIP2/NF-κB signaling cascade, and this intricate interplay could be modulated by several chemotherapeutic agents. 229 Baraniya et al 230 found the transcriptional alterations caused by Streptococcus mitis primarily exhibited an anticancer effect, marked by the inhibition of the HOTAIR regulatory pathway, JAK/STAT signaling, Cyclin/Cyclin-dependent kinases, and endothelin1 signaling pathways. Neutrophil extracellular traps (NETs), intricate lattice-like structures composed of DNA-histone complexes and proteins discharged by activated neutrophils, were initially identified for their essential involvement in antimicrobial resistance and immune regulation.…”

Section: Overview Of Oral Microbiota In Carcinogenesismentioning

confidence: 99%

Promising dawn in tumor microenvironment therapy: engineering oral bacteria

Wang,

Sun,

Hua

et al. 2024

Int J Oral Sci

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Despite decades of research, cancer continues to be a major global health concern. The human mouth appears to be a multiplicity of local environments communicating with other organs and causing diseases via microbes. Nowadays, the role of oral microbes in the development and progression of cancer has received increasing scrutiny. At the same time, bioengineering technology and nanotechnology is growing rapidly, in which the physiological activities of natural bacteria are modified to improve the therapeutic efficiency of cancers. These engineered bacteria were transformed to achieve directed genetic reprogramming, selective functional reorganization and precise control. In contrast to endotoxins produced by typical genetically modified bacteria, oral flora exhibits favorable biosafety characteristics. To outline the current cognitions upon oral microbes, engineered microbes and human cancers, related literatures were searched and reviewed based on the PubMed database. We focused on a number of oral microbes and related mechanisms associated with the tumor microenvironment, which involve in cancer occurrence and development. Whether engineering oral bacteria can be a possible application of cancer therapy is worth consideration. A deeper understanding of the relationship between engineered oral bacteria and cancer therapy may enhance our knowledge of tumor pathogenesis thus providing new insights and strategies for cancer prevention and treatment.

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Chemotherapeutic Drugs Induce Different Gut Microbiota Disorder Pattern and NOD/RIP2/NF-κB Signaling Pathway Activation That Lead to Different Degrees of Intestinal Injury

Abstract: Chemotherapy-induced intestinal injury limits the clinical use of drugs. Intestinal injury involves multiple signaling pathways and gut microbiota disruption.

Cited by 12 publications

References 66 publications

Amination Potentially Augments the Ameliorative Effect of Curcumin on Inhibition of the IL-6/Stat3/c-Myc Pathway and Gut Microbial Modulation in Colitis-Associated Tumorigenesis

Amination Potentially Augments the Ameliorative Effect of Curcumin on Inhibition of the IL-6/Stat3/c-Myc Pathway and Gut Microbial Modulation in Colitis-Associated Tumorigenesis

L‐Glutamine Substantially Improves 5‐Fluorouracil‐Induced Intestinal Mucositis by Modulating Gut Microbiota and Maintaining the Integrity of the Gut Barrier in Mice

Promising dawn in tumor microenvironment therapy: engineering oral bacteria

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