The Cancer Microbiome: Distinguishing Direct and Indirect Effects Requires a Systemic View

Xavier, João B.; Young, Vincent B.; Skufca, Joseph D.; Ginty, Fiona; Testerman, Traci L.; Pearson, Alexander T.; Macklin, Paul; Mitchell, Amir; Shmulevich, Ilya; Xie, Lei; Caporaso, J. Gregory; Crandall, Keith A.; Simone, Nicole L.; Godoy-Vitorino, Filipa; Griffin, Timothy J.; Whiteson, Katrine; Gustafson, Heather H.; Slade, Daniel J.; Schmidt, Thomas M.; Walther-Antonio, Marina; Korem, Tal; Webb-Robertson, Bobbie Jo M.; Styczynski, Mark P.; Johnson, W. Evan; Jobin, Christian; Ridlon, Jason M.; Koh, Andrew Y.; Yu, Michael; Kelly, Libusha; Wargo, Jennifer A.

doi:10.1016/j.trecan.2020.01.004

Cited by 173 publications

(135 citation statements)

References 107 publications

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“…Data from the prospective StuDoQ Pancreas registry of the German Society of General and Visceral Surgery yield a rate of 15% (12-19%) for major complications (Clavien-Dindo Classification (CDC) grades 3b and 4) in elective pancreatoduodenectomy [2]. A postoperative pancreatic fistula (POPF) is the most dangerous complication, and leads to a risk of sepsis, prolonged hospitalization, increased morbidity and mortality, and higher hospital costs [3][4][5][6]. Recently, the microbiome of the gut has not only been linked to anastomotic leakages after colorectal surgeries [7], but also to surgical complications in pancreatic operations [8].…”

Section: Introductionmentioning

confidence: 99%

“…Technical advances in detection (e.g., next-generation sequencing (NGS)) have changed our understanding of the structure and function of the microbiome, and the influence of the microbiome on immunity and cancer [10]. Altered local microbiota compositions in different cancer tissues may impact cancer therapy response [5]. In line with these concepts, compelling research has demonstrated that the gut microbiome is associated with impaired anastomotic healing in colorectal cancer (CRC), or higher postoperative complication rates in pancreatic surgery [8,11].…”

Section: Introductionmentioning

confidence: 99%

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Microbiome Patterns in Matched Bile, Duodenal, Pancreatic Tumor Tissue, Drainage, and Stool Samples: Association with Preoperative Stenting and Postoperative Pancreatic Fistula Development

Langheinrich

Wirtz

Kneis

et al. 2020

JCM

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Postoperative complications after pancreatic surgery are still a significant problem in clinical practice. The aim of this study was to characterize and compare the microbiomes of different body compartments (bile duct, duodenal mucosa, pancreatic tumor lesion, postoperative drainage fluid, and stool samples; preoperative and postoperative) in patients undergoing pancreatic surgery for suspected pancreatic cancer, and their association with relevant clinical factors (stent placement, pancreatic fistula, and gland texture). For this, solid (duodenal mucosa, pancreatic tumor tissue, stool) and liquid (bile, drainage fluid) biopsy samples of 10 patients were analyzed using 16s rRNA gene next-generation sequencing. Our analysis revealed: (i) a distinct microbiome in the different compartments, (ii) markedly higher abundance of Enterococcus in patients undergoing preoperative stent placement in the common bile duct, (iii) significant differences in the beta diversity between patients who developed a postoperative pancreatic fistula (POPF B/C), (iv) patients with POPF B/C were more likely to have bacteria belonging to the genus Enterococcus, and (v) differences in microbiome composition with regard to the pancreatic gland texture. The structure of the microbiome is distinctive in different compartments, and can be associated with the development of a postoperative pancreatic fistula.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Microbiome Patterns in Matched Bile, Duodenal, Pancreatic Tumor Tissue, Drainage, and Stool Samples: Association with Preoperative Stenting and Postoperative Pancreatic Fistula Development

Langheinrich

Wirtz

Kneis

et al. 2020

JCM

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“…This phenomenon is also seen with B. fragilis in colorectal cancer (38). Mice with colorectal cancer given F. nucleatum had more metastasis compared to controls, and increased expression of genes related to cell motility, such as E-cadherin (39). The antibiotic chloroquine reversed these effects (39).…”

Section: Relevance To Cancermentioning

confidence: 79%

The Role of the Microbiome in Cancer and Therapy Efficacy: Focus on Lung Cancer

et al. 2020

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The microbiome is extremely important for human health; more recently its role in the context of cancer became clear. Microbial effects range from enhancing cancer immunity and cancer therapy efficacy, to promoting cancer progression and inhibiting treatment efficacy. These broad implications led researchers to investigate these specific interactions, as well as how modification of the microbiome can improve cancer survival and treatment efficacy. While these interactions are better established for cancers such as gastric cancer, they are far less understood in others. As nonsmall cell lung cancer (NSCLC) makes up the majority of lung cancer cases, and is among the top causes of cancer deaths worldwide, understanding the mechanisms by which the microbiome may impact progression and treatment is crucial to improve patient survival and treatment response. A literature review was conducted to reveal the crosslink between human microbiome and lung cancer. This includes immune priming, induction of pro-or anti-tumor response, and the local effects of intra-tumoral microbiota. Overall, this is a complex multifactorial relationship, and there are broad implications as to how this knowledge can improve cancer treatment. Solutions include manipulation of the microbiome using probiotics, bacterial vaccines and antibiotics. Bacteria biomarkers may also be used as a diagnostic tool. The microbiome, defined as the collection of genomes from all the microorganisms found in a particular environment, is an emerging and widely studied factor in human health. Its implications in cancer are manifold (1). Specific microorganisms that are found within a specific environment (i.e., the microbiota) induce anti-tumor immunity through immune priming (1, 2). Dysbiosis, genotoxins, and inflammatory responses to microbiota are associated with cancer development (1). Additionally, cancer treatment efficacy can be enhanced or inhibited by intra-tumoral and gut microbiota (3-5). This knowledge leads to many questions regarding the interactions between the microbiome, cancer and cancer therapies. Most importantly, how can a better understanding of these interactions lead to improvement of current treatment efficacy? Compared to the gastrointestinal (GI) tract, the microbiota of the lung and other organs are far less understood (4, 6). Lung cancer is the first cause of death among oncologic patients and the second most common cancer worldwide (7). Investigating microbial-cancer relationships will aid in a better understanding of the role of microbes in mechanisms underlying tumorigenesis behind this as well as other cancers and hopefully improve treatment efficacy (4). These factors are poorly understood in lung cancer (3, 8, 9). Therefore, this review aims 4807 This article is freely accessible online.

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“…Despite this situation, a very exciting finding has been very recently [193] reported demonstrating that different tumor types have distinct microbiome signatures, which has important implications from a diagnostic point of view, and even more importantly that the tumor microbiota is composed of intracellular bacteria. Understanding the contribution of tumor type-specific, intracellular bacteria to the balance of the normal microbiota and the effects of antibiotics in the context of cancer risk and therapy efficiency will definitely require the application of system biology approaches [194].…”

Section: Conclusion and New Perspectivesmentioning

confidence: 99%

A Significant Question in Cancer Risk and Therapy: Are Antibiotics Positive or Negative Effectors? Current Answers and Possible Alternatives

Amadei

Notario

2020

Antibiotics

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Cancer is predominantly considered as an environmental disease caused by genetic or epigenetic alterations induced by exposure to extrinsic (e.g., carcinogens, pollutants, radiation) or intrinsic (e.g., metabolic, immune or genetic deficiencies). Over-exposure to antibiotics, which is favored by unregulated access as well as inappropriate prescriptions by physicians, is known to have led to serious health problems such as the rise of antibiotic resistance, in particular in poorly developed countries. In this review, the attention is focused on evaluating the effects of antibiotic exposure on cancer risk and on the outcome of cancer therapeutic protocols, either directly acting as extrinsic promoters, or indirectly, through interactions with the human gut microbiota. The preponderant evidence derived from information reported over the last 10 years confirms that antibiotic exposure tends to increase cancer risk and, unfortunately, that it reduces the efficacy of various forms of cancer therapy (e.g., chemo-, radio-, and immunotherapy alone or in combination). Alternatives to the current patterns of antibiotic use, such as introducing new antibiotics, bacteriophages or enzybiotics, and implementing dysbiosis-reducing microbiota modulatory strategies in oncology, are discussed. The information is in the end considered from the perspective of the most recent findings on the tumor-specific and intracellular location of the tumor microbiota, and of the most recent theories proposed to explain cancer etiology on the notion of regression of the eukaryotic cells and systems to stages characterized for a lack of coordination among their components of prokaryotic origin, which is promoted by injuries caused by environmental insults.

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The Cancer Microbiome: Distinguishing Direct and Indirect Effects Requires a Systemic View

Cited by 173 publications

References 107 publications

Microbiome Patterns in Matched Bile, Duodenal, Pancreatic Tumor Tissue, Drainage, and Stool Samples: Association with Preoperative Stenting and Postoperative Pancreatic Fistula Development

Microbiome Patterns in Matched Bile, Duodenal, Pancreatic Tumor Tissue, Drainage, and Stool Samples: Association with Preoperative Stenting and Postoperative Pancreatic Fistula Development

The Role of the Microbiome in Cancer and Therapy Efficacy: Focus on Lung Cancer

A Significant Question in Cancer Risk and Therapy: Are Antibiotics Positive or Negative Effectors? Current Answers and Possible Alternatives

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