Age-associated changes in the gut microbiome impact efficacy of tumor immunomodulatory treatments

Singh, Akansha; Ashar, Harshini; Ranjan, Ashish

doi:10.1016/j.exger.2023.112268

Cited by 3 publications

(2 citation statements)

References 39 publications

(44 reference statements)

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“…The genus Ruminococcaceae can increase the production of short-chain fatty acids (SCFAs), including acetic, propionic, and butyric acids, while reducing the release of inflammatory factors ( Wang et al, 2023 ). Additionally, Ruminiclostridium5 and Anaerotruncus have been linked to CD8+ and CD4+ T cells, and their abundance is negatively related to the levels of inflammatory TNF-α, IL-1β, and IL-6 ( Mao et al, 2023 ; Singh et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Gut microbiota and autoimmune neurologic disorders: a two-sample bidirectional Mendelian randomization study

Zhang,

Fang,

Zheng

et al. 2024

Front. Microbiol.

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BackgroundIncreasing evidence has suggested that alterations in the gut microbiome are correlated with autoimmune neurologic disorders, yet the causal relationship between them has yet to be established.MethodsFrom the published genome-wide association study (GWAS) summary statistics, we obtained data on the gut microbiota and three autoimmune neurologic disorders (Multiple Sclerosis, Guillain-Barré Syndrome, and Myasthenia Gravis). We then implemented a two-sample Mendelian Randomization (MR) to determine the causal relationship between the gut microbiota and the diseases. To validate the results, we conducted a series of sensitivity analyses. Finally, to verify the direction of causality, a reverse-causality analysis was done.ResultsWe discovered that a higher relative abundance of the genus Ruminococcus2 (OR: 1.213, 95% CI: 1.006–1.462, p = 0.043, PFDR = 0.048) and the genus Roseburia (OR: 1.255, 95% CI: 1.012–1.556, p = 0.038, PFDR = 0.048) were associated with a higher risk of MS. Furthermore, the higher the abundance of the class Mollicutes (OR: 3.016, 95% CI: 1.228–7.411, p = 0.016, PFDR = 0.021), the genus Eubacterium (hallii group) (OR: 2.787, 95% CI: 1.140–6.816, p = 0.025, PFDR = 0.025), and the phylum Tenericutes (OR: 3.016, 95% CI: 1.228–7.411, p = 0.016, PFDR = 0.021) was linked to a greater probability of GBS. Additionally, the higher the abundance of the genus Ruminococcaceae UCG005 (OR: 2.450, 95% CI: 1.072–5.598, p = 0.034, PFDR = 0.036), the genus Holdemania (OR: 2.437, 95% CI: 1.215–4.888, p = 0.012, PFDR = 0.024), genus Lachnoclostridium (OR: 3.681, 95% CI: 1.288–10.521, p = 0.015, PFDR = 0.025) and the genus Eubacterium (ruminantium group) (OR: 2.157, 95% CI: 1.211–3.843, p = 0.003, PFDR = 0.016) correlated with a greater chance of MG occurrence. No SNPs were identified as outliers through sensitivity analysis. Then, the results of the reverse MR analysis did not indicate any reverse causality.ConclusionOur findings demonstrate a causal relationship between the gut microbiota and three autoimmune neurologic disorders, providing novel insights into the mechanisms of these autoimmune neurologic disorders that are mediated by gut microbiota.

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Section: Discussionmentioning

confidence: 99%

Gut microbiota and autoimmune neurologic disorders: a two-sample bidirectional Mendelian randomization study

Zhang,

Fang,

Zheng

et al. 2024

Front. Microbiol.

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“…Furthermore, it has a positive correlation with cognitive function ( Guo et al, 2021 ). In tumor immunology studies, Ruminiclostridium has shown a negative correlation with CD8 + T cells ( Singh et al, 2023 ). In an autoimmune model of the central nervous system, medium-chain fatty acids (MCFAs) produced by this genus counteract the anti-inflammatory effects of short-chain fatty acids (SCFAs) by enhancing TH1 and TH17 cell differentiation ( Haghikia et al, 2015 ).Therefore, certain genera, such as Ruminiclostridium 9, may contribute to the initiation of DTC through analogous mechanisms, potentially by reducing short-chain fatty acidsand modulating the immune response.…”

Section: Discussionmentioning

confidence: 99%

Causal analysis of the gut microbiota in differentiated thyroid carcinoma: a two-sample Mendelian randomization study

Quan,

Zhang,

Wang

et al. 2023

Front. Genet.

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Objective: Numerous studies have highlighted an association between the gut microbiota (GM) and thyroid tumors. Employing Mendelian randomization methodology, we seek to elucidate the causal link between the gut microbiota and thyroid neoplasms.Methods: We procured data from the Mibiogen database encompassing 211 distinct gut microbiota taxa, alongside extensive genome-wide association studies (GWAS) summary data for differentiated thyroid carcinoma (DTC). Our principal analytical approach involved the application of the Inverse-Variance Weighted method (IVW) within the framework of Mendelian randomization. Simultaneously, we conducted sensitivity analyses to assess result heterogeneity, horizontal pleiotropy, and outcome stability.Results: IVW analysis revealed a dual role of the GM in thyroid carcinoma. The phylum Actinobacteria (OR, 0.249 [95% CI, 0.121–0.515]; p < 0.001) was associated with a decreased risk of DTC. Conversely, the genus Ruminiclostridium9 (OR, 11.276 [95% CI, 4.406–28.860]; p < 0.001), class Mollicutes (OR, 5.902 [95% CI, 1.768–19.699]; p = 0.004), genus RuminococcaceaeUCG004 (OR, 3.831 [95% CI, 1.516–9.683]; p = 0.005), genus Paraprevotella (OR, 3.536 [95% CI, 1.330–9.401]; p = 0.011), and phylum Tenericutes (OR, 5.902 [95% CI, 1.768–19.699]; p = 0.004) were associated with an increased risk of DTC.Conclusion: Our findings underscore that the presence of genus Ruminiclostridium9, class Mollicutes, genus RuminococcaceaeUCG004, genus Paraprevotella, and phylum Tenericutes is associated with an elevated risk of DTC, whereas the presence of the phylum Actinobacteria is linked to a decreased risk. These discoveries enhance our comprehension of the relationship between the GM and DTC.

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Mechanisms of myeloid-derived suppressor cell-mediated immunosuppression in colorectal cancer and related therapies

Nie,

Jing,

et al. 2024

World J Gastrointest Oncol

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Severe immunosuppression is a hallmark of colorectal cancer (CRC). Myeloid-derived suppressor cells (MDSCs), one of the most abundant components of the tumor stroma, play an important role in the invasion, metastasis, and immune escape of CRC. MDSCs create an immunosuppressive microenvironment by inhibiting the proliferation and activation of immunoreactive cells, including T and natural killer cells, as well as by inducing the proliferation of immunosuppressive cells, such as regulatory T cells and tumor-associated macrophages, which, in turn, promote the growth of cancer cells. Thus, MDSCs are key contributors to the emergence of an immunosuppressive microenvironment in CRC and play an important role in the breakdown of antitumor immunity. In this narrative review, we explore the mechanisms through which MDSCs contribute to the immunosuppressive microenvironment, the current therapeutic approaches and technologies targeting MDSCs, and the therapeutic potential of modulating MDSCs in CRC treatment. This study provides ideas and methods to enhance survival rates in patients with CRC.

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Age-associated changes in the gut microbiome impact efficacy of tumor immunomodulatory treatments

Cited by 3 publications

References 39 publications

Gut microbiota and autoimmune neurologic disorders: a two-sample bidirectional Mendelian randomization study

Gut microbiota and autoimmune neurologic disorders: a two-sample bidirectional Mendelian randomization study

Causal analysis of the gut microbiota in differentiated thyroid carcinoma: a two-sample Mendelian randomization study

Mechanisms of myeloid-derived suppressor cell-mediated immunosuppression in colorectal cancer and related therapies

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