Bacterial Translocation Contributes to Cachexia and Its Possible Pathway in Patients With Colon Cancer

Jiang, Yingjian; Lin, Jizheng; Zhang, Dianliang; Yu, Zhouman; Li, Qiurong; Jiang, Jun; Li, Jieshou

doi:10.1097/01.mcg.0000436437.83015.17

Cited by 14 publications

(6 citation statements)

References 18 publications

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“…The microbiota may be comprehensively involved in the alterations herein reported, and Jiang et al . have described increased bacterial translocation in patients with colon cancer; yet it was not our aim to address this matter presently.…”

Section: Discussionmentioning

confidence: 96%

Cancer cachexia induces morphological and inflammatory changes in the intestinal mucosa

Costa

Paula

Matos-Neto

et al. 2019

J cachexia sarcopenia muscle

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BackgroundCachexia is a multifactorial and multiorgan syndrome associated with cancer and other chronic diseases and characterized by severe involuntary body weight loss, disrupted metabolism, inflammation, anorexia, fatigue, and diminished quality of life. This syndrome affects around 50% of patients with colon cancer and is directly responsible for the death of at least 20% of all cancer patients. Systemic inflammation has been recently proposed to underline most of cachexia‐related symptoms. Nevertheless, the exact mechanisms leading to the initiation of systemic inflammation have not yet been unveiled, as patients bearing the same tumour and disease stage may or may not present cachexia. We hypothesize a role for gut barrier disruption, which may elicit persistent immune activation in the host. To address this hypothesis, we analysed the healthy colon tissue, adjacent to the tumour.MethodsBlood and rectosigmoid colon samples (20 cm distal to tumour margin) obtained during surgery, from cachectic (CC = 25) or weight stable (WSC = 20) colon cancer patients, who signed the informed consent form, were submitted to morphological (light microscopy), immunological (immunohistochemistry and flow cytometry), and molecular (quantification of inflammatory factors by Luminex® xMAP) analyses.ResultsThere was no statistical difference in gender and age between groups. The content of plasma interleukin 6 (IL‐6) and IL‐8 was augmented in cachectic patients relative to those with stable weight (P = 0.047 and P = 0.009, respectively). The number of lymphocytic aggregates/field in the gut mucosa was higher in CC than in WSC (P = 0.019), in addition to those of the lamina propria (LP) eosinophils (P < 0.001) and fibroblasts (P < 0.001). The area occupied by goblet cells in the colon mucosa was decreased in CC (P = 0.016). The M1M2 macrophages percentage was increased in the colon of CC, in relation to WSC (P = 0.042). Protein expression of IL‐7, IL‐13, and transforming growth factor beta 3 in the colon was significantly increased in CC, compared with WSC (P = 0.02, P = 0.048, and P = 0.048, respectively), and a trend towards a higher content of granulocyte‐colony stimulating factor in CC was also observed (P = 0.061). The results suggest an increased recruitment of immune cells to the colonic mucosa in CC, as compared with WSC, in a fashion that resembles repair response following injury, with higher tissue content of IL‐13 and transforming growth factor beta 3.ConclusionsThe changes in the intestinal mucosa cellularity, along with modified cytokine expression in cachexia, indicate that gut barrier alterations are associated with the syndrome.

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Section: Discussionmentioning

confidence: 96%

Cancer cachexia induces morphological and inflammatory changes in the intestinal mucosa

Costa

Paula

Matos-Neto

et al. 2019

J cachexia sarcopenia muscle

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“…Emergency surgeries and surgeries for trauma are considered high-risk for the development of bacterial translocation, thus requiring use of antibiotics in the perioperative period[ 35 ]. Patients with advanced colorectal and gastric cancer, potentially associated with cachexia, are also in need of prophylactic use of antibiotics due to immunological imbalance induced by the progressed disease[ 36 , 37 ]. Prophylaxis against bacterial translocation seems to be associated with better survival rates in cancer patients who undergo surgery[ 7 ].…”

Section: Bacterial Translocation Abdominal Surgery and Postoperative Sepsismentioning

confidence: 99%

Bacterial translocation in patients undergoing major gastrointestinal surgery and its role in postoperative sepsis

Doudakmanis¹,

Bouliaris²,

Kolla³

et al. 2021

WJGP

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Bacteria of the human intestinal microflora have a dual role. They promote digestion and are part of a defense mechanism against pathogens. These bacteria could become potential pathogens under certain circumstances. The term “bacterial translocation” describes the passage of bacteria of the gastrointestinal tract through the intestinal mucosa barrier to mesenteric lymph nodes and other organs. In some cases, the passage of bacteria and endotoxins could result in blood stream infections and in multiple organ failure. Open elective abdominal surgery more frequently results in malfunction of the intestinal barrier and subsequent bacterial translocation and blood stream infections than laparoscopic surgery. Postoperative sepsis is a common finding in patients who have undergone non-elective abdominal surgeries, including trauma patients treated with laparotomy. Postoperative sepsis is an emerging issue, as it changes the treatment plan in surgical patients and prolongs hospital stay. The association between bacterial translocation and postoperative sepsis could provide novel treatment options.

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“…LPS can cause a dysregulated inflammatory response leading to life-threatening organ dysfunction; a syndrome termed sepsis [3]. Increased levels of circulatory LPS are observed in patients with sepsis [4], elderly subjects [5,6] and individuals with diabetes mellitus [7], obesity [7], human immunodeficiency virus infection [8,9], cancer [10,11], liver cirrhosis [12], and end-stage kidney disease [13,14]. In the latter cases, increased LPS levels are caused by bacterial translocation from the intestinal tract to the circulation [15], a phenomenon known as metabolic endotoxemia [15].…”

Section: Introductionmentioning

confidence: 99%

Lipopolysaccharide inhibits myogenic differentiation of C2C12 myoblasts through the Toll-like receptor 4-nuclear factor-κB signaling pathway and myoblast-derived tumor necrosis factor-α

Ono

Sakamoto

2017

PLoS ONE

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BackgroundCirculating lipopolysaccharide (LPS) concentrations are often elevated in patients with sepsis or with various endogenous diseases that are associated with metabolic endotoxemia. Involuntary loss of skeletal muscle, termed muscle wasting, is commonly observed in these conditions, suggesting that circulating LPS might play an essential role in its development. Although impairment of muscle regeneration is an important determinant of skeletal muscle wasting, it is unclear whether LPS affects this process and, if so, by what mechanism. Here, we used the C2C12 myoblast cell line to investigate the effects of LPS on myogenesis.MethodsC2C12 myoblasts were grown to 80% confluence and induced to differentiate in the absence or presence of LPS (0.1 or 1 μg/mL); TAK-242 (1 μM), a specific inhibitor of Toll-like receptor 4 (TLR4) signaling; and a tumor necrosis factor (TNF)-α neutralizing antibody (5 μg/mL). Expression of a skeletal muscle differentiation marker (myosin heavy chain II), two essential myogenic regulatory factors (myogenin and MyoD), and a muscle negative regulatory factor (myostatin) was analyzed by western blotting. Nuclear factor-κB (NF-κB) DNA-binding activity was measured using an enzyme-linked immunosorbent assay.ResultsLPS dose-dependently and significantly decreased the formation of multinucleated myotubes and the expression of myosin heavy chain II, myogenin, and MyoD, and increased NF-κB DNA-binding activity and myostatin expression. The inhibitory effect of LPS on myogenic differentiation was reversible, suggesting that it was not caused by nonspecific toxicity. Both TAK-242 and anti-TNF-α reduced the LPS-induced increase in NF-κB DNA-binding activity, downregulation of myogenic regulatory factors, and upregulation of myostatin, thereby partially rescuing the impairment of myogenesis.ConclusionsOur data suggest that LPS inhibits myogenic differentiation via a TLR4–NF-κB-dependent pathway and an autocrine/paracrine TNF-α-induced pathway. These pathways may be involved in the development of muscle wasting caused by sepsis or metabolic endotoxemia.

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Bacterial Translocation Contributes to Cachexia and Its Possible Pathway in Patients With Colon Cancer

Abstract: This study suggests that BT may contribute to colon cancer in cachectic patients, and TJ could be the gateway to the possible pathway of BT.

Cited by 14 publications

References 18 publications

Cancer cachexia induces morphological and inflammatory changes in the intestinal mucosa

Cancer cachexia induces morphological and inflammatory changes in the intestinal mucosa

Bacterial translocation in patients undergoing major gastrointestinal surgery and its role in postoperative sepsis

Lipopolysaccharide inhibits myogenic differentiation of C2C12 myoblasts through the Toll-like receptor 4-nuclear factor-κB signaling pathway and myoblast-derived tumor necrosis factor-α

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