Bacterial biofilm formation inside colonic crypts may accelerate colorectal carcinogenesis

Raskov, Hans; Kragh, Kasper Nørskov; Bjarnsholt, Thomas; Alamili, Mahdi; Gögenur, Ismail

doi:10.1186/s40169-018-0209-2

Cited by 21 publications

(15 citation statements)

References 7 publications

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“…In humans, bacterial biofilms and mucus invasive bacteria have recently been reported to be a characteristic feature of right‐sided tumors 5,16,17 . Biopsies of the normal‐appearing mucosa from these patients also display biofilms, which are uncommonly seen in patients with distal tumors or healthy controls.…”

Section: Introductionmentioning

confidence: 99%

Crypt residing bacteria and proximal colonic carcinogenesis in a mouse model of Lynch syndrome

Lang

Baumgartner

Rożalska

et al. 2020

Intl Journal of Cancer

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Colorectal cancer is a multifactorial disease involving inherited DNA mutations, environmental factors, gut inflammation and intestinal microbiota. Certain germline mutations within the DNA mismatch repair system are associated with Lynch syndrome tumors including right‐sided colorectal cancer with mucinous phenotype and presence of an inflammatory infiltrate. Such tumors are more often associated with bacterial biofilms, which may contribute to disease onset and progression. Inflammatory bowel diseases are also associated with colorectal cancer and intestinal dysbiosis. Herein we addressed the question, whether inflammation can aggravate colorectal cancer development under mismatch repair deficiency. MSH2loxP/loxP Vill‐cre mice were crossed into the IL‐10−/− background to study the importance of inflammation and mucosal bacteria as a driver of tumorigenesis in a Lynch syndrome mouse model. An increase in large bowel tumorigenesis was found in double knockout mice both under conventional housing and under specific pathogen‐free conditions. This increase was mostly due to the development of proximal tumors, a hotspot for tumorigenesis in Lynch syndrome, and was associated with a higher degree of inflammation. Additionally, bacterial invasion into the mucus of tumor crypts was observed in the proximal tumors. Inflammation shifted fecal and mucosal microbiota composition and was associated with enrichment in Escherichia‐Shigella as well as Akkermansia, Bacteroides and Parabacteroides genera in fecal samples. Tumor‐bearing double knockout mice showed a similar enrichment for Escherichia‐Shigella and Parabacteroides. Lactobacilli, Lachnospiraceae and Muribaculaceae family members were depleted upon inflammation. In summary, chronic inflammation aggravates colonic tumorigenesis under mismatch repair deficiency and is associated with a shift in microbiota composition.

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Section: Introductionmentioning

confidence: 99%

Crypt residing bacteria and proximal colonic carcinogenesis in a mouse model of Lynch syndrome

Lang

Baumgartner

Rożalska

et al. 2020

Intl Journal of Cancer

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“…The phenomenon of quorum sensing regulates the process of biofilm formation, which will further enable the bacteria to persist in the host cells and escape the host defense immune system [ 112 ]. In addition, the biofilm formation can result in the progression of colon and colorectal carcinogenesis [ 113 ]. Biofilm can be exploited as potential anti-cancer agents due to its ability to deliver therapeutics and to curb the spread of metastatic tumors.…”

Section: Mechanism Of Tumor Suppressionmentioning

confidence: 99%

Microbes as Medicines: Harnessing the Power of Bacteria in Advancing Cancer Treatment

Sawant

Patil

Gupta

et al. 2020

IJMS

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Conventional anti-cancer therapy involves the use of chemical chemotherapeutics and radiation and are often non-specific in action. The development of drug resistance and the inability of the drug to penetrate the tumor cells has been a major pitfall in current treatment. This has led to the investigation of alternative anti-tumor therapeutics possessing greater specificity and efficacy. There is a significant interest in exploring the use of microbes as potential anti-cancer medicines. The inherent tropism of the bacteria for hypoxic tumor environment and its ability to be genetically engineered as a vector for gene and drug therapy has led to the development of bacteria as a potential weapon against cancer. In this review, we will introduce bacterial anti-cancer therapy with an emphasis on the various mechanisms involved in tumor targeting and tumor suppression. The bacteriotherapy approaches in conjunction with the conventional cancer therapy can be effective in designing novel cancer therapies. We focus on the current progress achieved in bacterial cancer therapies that show potential in advancing existing cancer treatment options and help attain positive clinical outcomes with minimal systemic side-effects.

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“…Besides from the vermiform appendix, presence of mixedspecies biofilms in the healthy gut mucosa is still debated (Tytgat et al, 2019), though some studies have shown bacterial biofilms in close proximity to the epithelial lining, but only in the appendixes (Palestrant et al, 2004). Presence of biofilms in the colonic crypts has been described for intestinal diseases such as colorectal cancer (Raskov et al, 2018) and visualization of mixed-species biofilms has likewise been reported (Dejea et al, 2014).…”

Section: Gut Microbiotamentioning

confidence: 99%

Do Mixed-Species Biofilms Dominate in Chronic Infections?–Need for in situ Visualization of Bacterial Organization

Kvich

Burmølle

Bjarnsholt

et al. 2020

Front. Cell. Infect. Microbiol.

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Chronic infections present a serious economic burden to health-care systems. The severity and prevalence of chronic infections are continuously increasing due to an aging population and an elevated number of lifestyle related diseases such as diabetes. Treatment of chronic infections has proven difficult, mainly due to the presence of biofilms that render bacteria more tolerant toward antimicrobials and the host immune response. Chronic infections have been described to harbor several different bacterial species and it has been hypothesized that microscale interactions and mixed-species consortia are present as described for most natural occurring biofilms i.e., aquatic systems and industrial settings, but also for some commensal human biofilms i.e., the mouth microbiota. However, the presence of mixed-species biofilms in chronic infections is most often an assumption based on culture-based methods and/or by means of molecular approaches, such as PCR and sequencing performed from homogenized bulk tissue samples. These methods disregard the spatial organization of the bacterial community and thus valuable information on biofilm aggregate composition, spatial organization, and possible interactions between different species is lost. Hitherto, only few studies have made visual in situ presentations of mixed-species biofilms in chronic infections, which is pivotal for the description of bacterial composition, spatial distribution, and interspecies interaction on the microscale. In order for bacteria to interact (synergism, commensalism, mutualism, competition, etc.) they need to be in close proximity to each other on the scale where they can affect e.g., solute concentrations. We argue that visual proof of mixed species biofilms in chronic infections is scarce compared to what is seen in e.g., environmental biofilms and call for a debate on the importance of mixed-species biofilm in chronic infections.

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Bacterial biofilm formation inside colonic crypts may accelerate colorectal carcinogenesis

Cited by 21 publications

References 7 publications

Crypt residing bacteria and proximal colonic carcinogenesis in a mouse model of Lynch syndrome

Crypt residing bacteria and proximal colonic carcinogenesis in a mouse model of Lynch syndrome

Microbes as Medicines: Harnessing the Power of Bacteria in Advancing Cancer Treatment

Do Mixed-Species Biofilms Dominate in Chronic Infections?–Need for in situ Visualization of Bacterial Organization

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