Structural Change in Microbiota by a Probiotic Cocktail Enhances the Gut Barrier and Reduces Cancer via TLR2 Signaling in a Rat Model of Colon Cancer

Kuugbee, Eugene Dogkotenge; Shang, Xiaona; Gamallat, Yaser; Bamba, Djibril; Awadasseid, Annoor; Suliman, Mohammed A; Zang, Shizhu; Ma, Yufang; Chiwala, Gift; Xin, Yi; Shang, Dong

doi:10.1007/s10620-016-4238-7

Cited by 132 publications

(97 citation statements)

References 74 publications

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“…That finding suggested that constitutive luminal factors, such as microbial flora, were more important in the regulation of TLR expression than tumor‐related factors. Based on our present finding of a correlation between serum TLR2 levels and TLR2 expression in normal colorectal mucosa, combined with recent evidence that probiotic flora administration could induce TLR2 expression and downregulate inflammation in colon mucosa, we speculate that, in a subset of patients, it might be possible to downregulate systemic inflammation in CRC by modifying the luminal flora .…”

Section: Discussionsupporting

confidence: 69%

Serum TLR2 and TLR4 levels in colorectal cancer and their association with systemic inflammatory markers, tumor characteristics, and disease outcome

Paarnio

Tuomisto

Väyrynen

et al. 2019

APMIS

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Paarnio K, Tuomisto A, V€ ayrynen SA, V€ ayrynen JP, Klintrup K, Ohtonen P, M€ akinen MJ, M€ akel€ a J, Karttunen TJ. Serum TLR2 and TLR4 levels in colorectal cancer and their association with systemic inflammatory markers, tumor characteristics, and disease outcome. APMIS 2019; 127: 561-569.Toll-like receptors (TLRs) are involved in colorectal cancer (CRC) pathogenesis. However, the significance of serum TLR concentrations in CRC is unknown. We analyzed serum TLR2 and TLR4 concentrations with ELISA in preoperative samples from 118 patients with CRC and 88 matched controls. We also assessed tissue TLR expression with immunohistochemistry and by detecting serum determinants of systemic inflammation. Most participants (>70%) had undetectable serum TLR2. The mean serum TLR4 levels were lower in patients than in controls (1.1 vs 1.8 ng/mL; p = 0.015). Undetectable TLR4 was more common in stage I (39%) than in stages II-IV (11%, p < 0.001). TLR2 or TLR4 expression in tumor cells did not correlate with serum levels, but abundant TLR2 expression in normal colon epithelium was associated with detectable serum TLR2 (p = 0.034). Undetectable serum TLR2 was linked to high modified Glasgow prognostic scores (p = 0.010), high CRP levels (p = 0.013), blood vessel invasion (p = 0.013), and tended to be associated with worse 5-year survival (p = 0.052). In conclusion, serum TLR2 levels were inversely associated with systemic inflammation in patients with CRC. Moreover, serum TLR2 levels might depend more on normal colorectal mucosa contributions than on tumor tissue contributions. Further studies are required to assess the prognostic value of serum TLR2.

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Section: Discussionsupporting

confidence: 69%

Serum TLR2 and TLR4 levels in colorectal cancer and their association with systemic inflammatory markers, tumor characteristics, and disease outcome

Paarnio

Tuomisto

Väyrynen

et al. 2019

APMIS

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“…| 5615 enhancement induced by DAMPs released from chemical drug-treated tumor cells (Fang et al, 2014). It has also been reported that the anticancer effect of a probiotic cocktail is mediate by increasing TLR2 signaling in a rat model of colon cancer (Kuugbee et al, 2016).…”

Section: Tlr2/4mentioning

confidence: 97%

Toll like receptor signaling pathway as a potential therapeutic target in colorectal cancer

Moradi‐Marjaneh

Hassanian

Fiuji

et al. 2018

Journal Cellular Physiology

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Toll like receptor (TLR) signaling is involved in activating innate and adaptive immune responses and plays a critical role in inflammation-induced diseases such as colorectal cancer (CRC). Dysregulation of this signaling pathway can result in disturbance of epithelial layer hemostasis, chronic inflammatory, excessive repair responses, and development of CRC. There is now substantial evidence for the benefit of targeting of this pathway in cancer treatment, and several agents have been approved, such as BCG (Bacillus Calmette Guérin), MPL (monophosphoryl lipid A) and imiquimod. This review summarizes the current knowledge about the different functions of TLRs on tumor cells and their application in cancer therapy with particular emphasis on recent preclinical and clinical research in treatment of CRC.

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“…On the contrary, inflammatory biomarkers and side effects of chemotherapy were reduced in these patients (Golkhalkhali et al, 2018;Kotzampassi et al, 2015;Krebs, 2016;Z. Liu et al, 2015;Mego et al, 2015; reducing colitis, (l) increasing apoptosis, (m) increasing tumor suppressor miRNAs and, (n) increasing CXCR2 signaling (Agah et al, 2018;Arthur et al, 2013;Asha & Gayathri, 2012;Donohoe et al, 2014;Gamallat et al, 2016;Kahouli, Malhotra, Westfall, Alaoui-Jamali, & Prakash, 2017;Klewicka, Nowak, Zduńczyk, Cukrowska, & Błasiak, 2012;Kuugbee et al, 2016;Mendes et al, 2018;Mi et al, 2017;Mohania, Kansal, Kruzliak, & Kumari, 2014;Song et al, 2018;Talero et al, 2015;Walia, Kamal, Dhawan, & Kanwar, 2018;Zhang et al, 2015). studies include: intestinal microflora normalization, improvement of the gastrointestinal barrier, reduction of tumor formation, proliferation and growth of CRC cells and metastasis, reduction inflammatory responses, bacterial infection before and after colon cancer surgery.…”

Section: Human Studiesmentioning

confidence: 99%

Importance of probiotics in the prevention and treatment of colorectal cancer

Eslami

Yousefi

Kokhaei

et al. 2019

Journal Cellular Physiology

202

117

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Colorectal cancer (CRC) remains one of the most common and deadly cancers. Intestinal gut microflora is important to maintain and contributes to several intestinal functions, including the development of the mucosal immune system, absorption of complex macromolecules, synthesis of amino acids/vitamins and the protection against pathogenic microorganisms. It is well known that the gut microbiota changes or dysbiosis may have an essential impact in the initiation and promotion of chronic inflammatory pathways and also have a profound different genetic and epigenetic alterations leading to dysplasia, clonal expansion, and malignant transformation. Probiotic bacteria has antitumor activity with various mechanisms such as nonspecific physiological and immunological mechanisms. This review evaluates the effects of microbiota and probiotics in clinical trials, in vitro and animal model studies that have explored how probiotic against cancer development and also discusses the possible immunomodulatory mechanisms. Several mechanisms alteration of the intestinal microflora; inactivation of cancerogenic compounds; competition with putrefactive and pathogenic microbiota; improvement of the host's immune response; antiproliferative effects via regulation of apoptosis and cell differentiation; fermentation of undigested food; inhibition of tyrosine kinase; reduces the enteropathogenic complications before and after colon cancer surgery and improve diarrhea and it's have been able to create the integrity of gut mucosal and have stimulatory effects on the systemic immune system and prevent the CRC metastasis. Research in clinical trials encouraging findings that support a role of probiotics in CRC prevention and improve the safety and effectiveness of cancer therapy even though additional clinical research is still necessary.

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Structural Change in Microbiota by a Probiotic Cocktail Enhances the Gut Barrier and Reduces Cancer via TLR2 Signaling in a Rat Model of Colon Cancer

Abstract: Administration of LBB modulates the gut microbiota and reduces colon cancer development by decreasing tumor incidence, multiplicity/count, and volume via enhanced TLR2-improved gut mucosa epithelial barrier integrity and suppression of apoptosis and inflammation.

Cited by 132 publications

References 74 publications

Serum TLR2 and TLR4 levels in colorectal cancer and their association with systemic inflammatory markers, tumor characteristics, and disease outcome

Serum TLR2 and TLR4 levels in colorectal cancer and their association with systemic inflammatory markers, tumor characteristics, and disease outcome

Toll like receptor signaling pathway as a potential therapeutic target in colorectal cancer

Importance of probiotics in the prevention and treatment of colorectal cancer

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