Colorectal Cancer and Probiotics: Are Bugs Really Drugs?

Lamichhane, Purushottam; Maiolini, Morgan; Alnafoosi, Omar; Hussein, Sedra; Alnafoosi, Hasan; Umbela, Stewart; Richardson, Tayanna; Alla, Nevien; Lamichhane, Narottam; Subhadra, Bobban; Deshmukh, Rahul

doi:10.3390/cancers12051162

Cited by 32 publications

(16 citation statements)

References 127 publications

(234 reference statements)

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“…Colorectal cancer is a heterogeneous disease associated with genetic mutations, age, family history, ethnicity, and lifestyle. 273 – 278 The downregulation of GSDMC led to significant decreases in the proliferation and of colorectal cancer cells, while GSDMC overexpression promoted cell proliferation, tumorigenesis suggesting that GSDMC may be a promising therapeutic target in colorectal cancer. 54 GSDMD was downregulated in carcinoma cells, while it was slightly overexpressed in normal colorectal epithelial cells.…”

Section: Role Of Pyroptosis In Tumorsmentioning

confidence: 99%

Pyroptosis: mechanisms and diseases

Zhang

Liu

et al. 2021

Sig Transduct Target Ther

1,145

799

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Currently, pyroptosis has received more and more attention because of its association with innate immunity and disease. The research scope of pyroptosis has expanded with the discovery of the gasdermin family. A great deal of evidence shows that pyroptosis can affect the development of tumors. The relationship between pyroptosis and tumors is diverse in different tissues and genetic backgrounds. In this review, we provide basic knowledge of pyroptosis, explain the relationship between pyroptosis and tumors, and focus on the significance of pyroptosis in tumor treatment. In addition, we further summarize the possibility of pyroptosis as a potential tumor treatment strategy and describe the side effects of radiotherapy and chemotherapy caused by pyroptosis. In brief, pyroptosis is a double-edged sword for tumors. The rational use of this dual effect will help us further explore the formation and development of tumors, and provide ideas for patients to develop new drugs based on pyroptosis.

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Section: Role Of Pyroptosis In Tumorsmentioning

confidence: 99%

Pyroptosis: mechanisms and diseases

Zhang

Liu

et al. 2021

Sig Transduct Target Ther

1,145

799

View full text Add to dashboard Cite

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“…The continuous production and secretion of pro-inflammatory cytokines such as IL-6, IL-17, and TNF have been associated with human colonic carcinogenesis [ 47 ]. According to Lamichhane et al (2020) [ 48 ], probiotics administration can effectively modulate immune functions in the gut by reducing the production of tumor-promoting cytokines. The present study showed that the highest concentrations of the pro-inflammatory cytokines IL-6 and IL-17 were found in the colon tissue of animals subjected to DMH treatment only (GNI group), whereas the intervention with the probiotic candidate L. paracasei DTA81 reduced significantly the levels of both cytokines.…”

Section: Discussionmentioning

confidence: 99%

“…Although Caspase 3 levels did not differ among the experimental groups, additional pro-apoptotic genes, such as Bax and Caspase 9, may also contribute to the balance between proliferation and apoptosis of tumor cells. With regard to L. paracasei strains and apoptosis’ regulation, their activities are attributed to different mechanisms such as by stimulation of proapoptotic genes [ 48 ], the promotion of cell cycle arrest, and calreticulin translocation via the generation of ROS, observed for L. paracasei M5L [ 43 ], and by modulating the expression of specific Bcl-2 family proteins as hypothesized to the strain L. paracasei K5 [ 83 ]. Immunomodulation is another possible mechanism that contributes to the proapoptotic activity induced by probiotics, especially increased TNF production [ 67 ], as observed in the present study for the LGG group.…”

Section: Discussionmentioning

confidence: 99%

Chemoprevention of DMH-Induced Early Colon Carcinogenesis in Male BALB/c Mice by Administration of Lactobacillus Paracasei DTA81

et al. 2020

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We evaluated the effects of the probiotic candidate Lactobacillus paracasei DTA81 (DTA81) on liver oxidative stress, colonic cytokine profile, and gut microbiota in mice with induced early colon carcinogenesis (CRC) by 1,2-dimethylhydrazine (DMH). Animals were divided into four different groups (n = 6) and received the following treatments via orogastric gavage for 8 weeks: Group skim milk (GSM): 300 mg/freeze-dried skim milk/day; Group L. paracasei DTA81 (DTA81): 3 × 109 colony-forming units (CFU)/day; Group Lactobacillus rhamnosus GG (LGG): 3 × 109 CFU/day; Group non-intervention (GNI): 0.1 mL/water/day. A single DMH dose (20 mg/kg body weight) was injected intraperitoneally (i.p), weekly, in all animals (seven applications in total). At the end of the experimental period, DTA81 intake reduced hepatic levels of carbonyl protein and malondialdehyde (MDA). Moreover, low levels of the pro-inflammatory cytokines Interleukin-6 (IL-6) and IL-17, as well as a reduced expression level of the proliferating cell nuclear antigen (PCNA) were observed in colonic homogenates. Lastly, animals who received DTA81 showed an intestinal enrichment of the genus Ruminiclostridium and increased concentrations of caecal acetic acid and total short-chain fatty acids. In conclusion, this study indicates that the administration of the probiotic candidate DTA81 can have beneficial effects on the initial stages of CRC development.

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“…Moreover, although synbiotic supplementation with Bifidobacterium lactis and resistant starch produced unique changes in the fecal microflora in another study of patients with colorectal cancer, it did not significantly alter any other fecal, serum, or epithelial biomarkers [ 73 ]. The authors of this study underscored the need to consider the patient’s family history and lifestyle, including diet, smoking, and other factors, before treatment with probiotics or synbiotics, and that further, in-depth research should be undertaken to gain a better understanding of the clinical value of these agents in colorectal cancer [ 74 ].…”

Section: Interplay Between the Gut Microbiome And Radiotherapy Toxicimentioning

confidence: 99%

Radiotherapy and the gut microbiome: facts and fiction

2021

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An ever-growing body of evidence has linked the gut microbiome with both the effectiveness and the toxicity of cancer therapies. Radiotherapy is an effective way to treat tumors, although large variations exist among patients in tumor radio-responsiveness and in the incidence and severity of radiotherapy-induced side effects. Relatively little is known about whether and how the microbiome regulates the response to radiotherapy. Gut microbiota may be an important player in modulating “hot” versus “cold” tumor microenvironment, ultimately affecting treatment efficacy. The interaction of the gut microbiome and radiotherapy is a bidirectional function, in that radiotherapy can disrupt the microbiome and those disruptions can influence the effectiveness of the anticancer treatments. Limited data have shown that interactions between the radiation and the microbiome can have positive effects on oncotherapy. On the other hand, exposure to ionizing radiation leads to changes in the gut microbiome that contribute to radiation enteropathy. The gut microbiome can influence radiation-induced gastrointestinal mucositis through two mechanisms including translocation and dysbiosis. We propose that the gut microbiome can be modified to maximize the response to treatment and minimize adverse effects through the use of personalized probiotics, prebiotics, or fecal microbial transplantation. 16S rRNA sequencing is the most commonly used approach to investigate distribution and diversity of gut microbiome between individuals though it only identifies bacteria level other than strain level. The functional gut microbiome can be studied using methods involving metagenomics, metatranscriptomics, metaproteomics, as well as metabolomics. Multiple ‘-omic’ approaches can be applied simultaneously to the same sample to obtain integrated results. That said, challenges and remaining unknowns in the future that persist at this time include the mechanisms by which the gut microbiome affects radiosensitivity, interactions between the gut microbiome and combination treatments, the role of the gut microbiome with regard to predictive and prognostic biomarkers, the need for multi “-omic” approach for in-depth exploration of functional changes and their effects on host-microbiome interactions, and interactions between gut microbiome, microbial metabolites and immune microenvironment.

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Colorectal Cancer and Probiotics: Are Bugs Really Drugs?

Cited by 32 publications

References 127 publications

Pyroptosis: mechanisms and diseases

Pyroptosis: mechanisms and diseases

Chemoprevention of DMH-Induced Early Colon Carcinogenesis in Male BALB/c Mice by Administration of Lactobacillus Paracasei DTA81

Radiotherapy and the gut microbiome: facts and fiction

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