scholarly journals Effects of enriched environment and probiotics on the intestinal mucosal barrier and the brain-gut axis in rats with colorectal cancer

2020 ◽  
Author(s):  
Dun Liu ◽  
Wu Xian-Yi ◽  
Huang Si-Ting

Abstract Background Enriched environment is a paradigm where animals are introduced to novel, complex, and stimulating surroundings that can protect the intestinal mucosal barrier and regulate the expression of brain-gut peptides. Probiotics can effectively protect the intestinal mucosal barrier and regulate brain-gut axis activity in colorectal cancer patients. This study assessed the effects of probiotics, enriched environment, and joint intervention on the intestinal mucosal barrier and brain-gut axis in rats with colorectal cancer. Methods We used a rat model of 1,2-dimethylhydrazine-induced colorectal cancer. Rats were housed in four different conditions for 2 weeks: enriched environment, probiotic,joint condition and normal condition. Each rat was weighed, and the intestinal mucosa and plasma levels of tumor TNF-α, IL-6, IL-10, ghrelin, CRF, occludin, BT, SIgA and the morphology of the intestinal mucosa were measured. Results enriched environment was beneficial regarding bacteria translation, plasma and intestinal mucosa levels of cytokines, plasma CRF levels, villi length and width of intestinal mucosa and hypothalamus ghrelin compared to probiotic (P < 0.05). There were no statistical differences between the enriched environment and the other groups regarding occludin, SIgA, muscle thickness or intestinal mucosa ghrelin (P > 0.05). Conclusions The effect of enriched environment was better than probiotic, especially in the intestinal mucosal immune and biological barrier in rats with colorectal cancer. However, the combination of the two was not as effective as enriched environment. In future studies, we can investigate the role of environment and probiotics in SIgA, intestinal mucosal mechanical barrier and body weight by extending the intervention time and enlarging the sample size.

2018 ◽  
Vol 243 (15-16) ◽  
pp. 1185-1198 ◽  
Author(s):  
Dun Liu ◽  
Xiao-Ying Jiang ◽  
Lan-Shu Zhou

An enriched environment (EE) is an animal housing technique in which animals are given increased amounts of space, physical activity, and social interaction. Currently, researchers studying EE focus mainly on its effects within the context of neurological diseases. However, little is known about how EE affects the intestinal mucosal barrier. This study assessed the effects of EE on the intestinal mucosal barrier in rats with colorectal cancer. A rat model of 1,2-dimethylhydrazine (DMH)-induced colorectal cancer was used. The rats were housed in eight conditions for eight weeks: EE, large cages containing eight rats with stimulating objects; enlarged space and socially enriched conditions (ES), large cages containing eight rats; enlarged space and cognition enriched conditions (EC), large cages containing one rat with stimulating objects; enlarged space enriched conditions (E), large cages containing one rat; cognition and socially enriched conditions (CS), four to five rats housed in standard cages containing stimulating objects; cognition enriched conditions (C), rats housed individually in small-size cages containing stimulating objects; socially enriched conditions (S), standard cages containing four rats; and normal conditions (blank group, B). We determined the weight of each rat, measured the intestinal mucosa and plasma levels of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), interleukin 10 (IL-10), ghrelin, corticotropin-releasing factor (CRF), occludin, bacterial translocation (BT), and secretory immunoglobulin A (SIgA), and assessed the morphology of the intestinal mucosa. On the whole, the combination of cognitive stimulus and social support was better than the combination of three factors in maintenance of the intestinal mucosal immune barrier and brain–gut peptide. The combination of all three factors and combination of cognitive training and social support were more effective than any single factor. Future studies are needed to study the effects of an EE on body weight, brain–gut peptide, and the intestinal mucosa biological barrier. Impact statement An enriched environment (EE) is an animal housing technique where animals are given increased amounts of space, physical activity, and social interaction. Presently, researchers studying EEs focus mainly on their effects within the context of neurological diseases. However, little is known about how EEs affect the intestinal mucosal barrier. This study assessed the effects of an EE on the intestinal mucosal barrier in rats with colorectal cancer.


2021 ◽  
Author(s):  
Qingsheng Niu ◽  
Fang Liu ◽  
Jun Zhang ◽  
Xiaojun Yang ◽  
Xiaohong Wang

Abstract The unique features of post–cardiac arrest pathophysiology are often superimposed on the disease or injury, causing the cardiac arrest, as well as underlying comorbidities. Exogenous carbon monoxide (CO) was reported to reduce ischemia-reperfusion injury (IRI). This study aimed to assess the effects of CO releasing molecule-2 (CORM-2) on intestinal mucosal barrier function after cardiopulmonary resuscitation (CPR) in rats. For this purpose, we established a rat model of asphyxiation-induced cardiac arrest and resuscitation to study intestinal IRI, and measured the serum level of intestinal fatty-acid binding protein (I-FABP). The expression levels of claudin-3, occludin, ZO-1, tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), and nuclear factor kappa B (NF-κB) p65 were detected by Western blotting. CORM-2 up-regulated the expression levels of tight junction proteins (claudin-3, occludin, and ZO-1) in intestinal mucosa, leading to the reduction of the permeability of intestinal mucosa and reduced the release of proinflammatory cytokines. Besides, the CORM-2 exhibited anti-inflammatory effects by regulating the TNF-α/NF-κB pathway. In conclusion, CORM-2 treatment is clinically significant, preventing intestinal mucosal damage as a result of IRI during CPR.


Author(s):  
Sridhar Muthusami ◽  
Ilangovan Ramachandran ◽  
Sneha Krishnamoorthy ◽  
Yuvaraj Sambandam ◽  
Satish Ramalingam ◽  
...  

: The development of colorectal cancer (CRC) is a multi-stage process. The inflammation of the colon as in inflammatory bowel disease (IBD) such as ulcerative colitis (UC) or Crohn’s disease (CD) is often regarded as the initial trigger for the development of CRC. Many cytokines such as tumor necrosis factor alpha (TNF-α) and several interleukins (ILs) are known to exert proinflammatory actions, and inflammation initiates or promotes tumorigenesis of various cancers, including CRC through differential regulation of microRNAs (miRNAs/miRs). miRNAs can be oncogenic miRNAs (oncomiRs) or anti-oncomiRs/tumor suppressor miRNAs, and they play key roles during colorectal carcinogenesis. However, the functions and molecular mechanisms of regulation of miRNAs involved in inflammation-associated CRC are still anecdotal and largely unknown. Consolidating the published results and offering perspective solutions to circumvent CRC, the current review is focused on the role of miRNAs and their regulation in the development of CRC. We have also discussed the model systems adapted by researchers to delineate the role of miRNAs in inflammation-associated CRC.


Author(s):  
Sridhar Muthusami ◽  
R. Ileng Kumaran ◽  
Kokelavani Nampalli Babu ◽  
Sneha Krishnamoorthy ◽  
Akash Guruswamy ◽  
...  

: Chronic inflammation can lead to the development of many diseases including cancer. Inflammatory bowel disease (IBD) that includes both ulcerative colitis (UC) and Crohn's disease (CD) are risk factors for the development of colorectal cancer (CRC). Many cytokines produced primarily by the gut immune cells either during or in response to localized inflammation in the colon and rectum are known to stimulate the complex interactions between the different cell types in the gut environment resulting in acute inflammation. Subsequently, chronic inflammation together with genetic and epigenetic changes has been shown to lead to the development and progression of CRC. Various cell types present in the colon such as enterocytes, Paneth cells, goblet cells and macrophages express receptors for inflammatory cytokines and respond to tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6 and other cytokines. Among the several cytokines produced, TNF-α and IL-1β are the key proinflammatory molecules that play critical roles in the development of CRC. The current review is intended to consolidate the published findings to focus on the role of proinflammatory cytokines, namely TNF-α and IL-1β, on inflammation (and the altered immune response) in the gut, to better understand the development of CRC in IBD, using various experimental model systems, preclinical and clinical studies. Moreover, this review also highlights the current therapeutic strategies available (monotherapy and combination therapy), to alleviate the symptoms or treat inflammationassociated CRC by using monoclonal antibodies or aptamers to block proinflammatory molecules, inhibitors of tyrosine kinases in inflammatory signaling cascade, competitive inhibitors of proinflammatory molecules, and the nucleic acid drugs like small activating RNAs (saRNAs) or microRNA (miRNA) mimics to activate tumor suppressor or repress oncogene/proinflammatory cytokine gene expression.


2014 ◽  
Vol 29 (1) ◽  
pp. e30-e39 ◽  
Author(s):  
Ariel Zwenger ◽  
Martin Rabassa ◽  
Sandra Demichelis ◽  
Gabriel Grossman ◽  
Amada Segal-Eiras ◽  
...  

Aim Colorectal cancer (CRC) is one of the most prevalent malignancies in Argentina with 11,043 new cases and 6,596 deaths estimated to have occurred in 2008. The present study was developed to clarify the differential expression of MUC1, MUC2, sLex, and sLea in colorectal cancer patients and their relationship with survival and clinical and histological features. Methods Ninety primary tumor samples and 43 metastatic lymph nodes from CRC patients were studied; follow-up was documented. Twenty-six adenoma and 68 histological normal mucosa specimens were analyzed. An immunohistochemical approach was applied and statistical analysis was performed. Results In tumor samples, MUC1, sLea, and sLex were highly expressed (94%, 67%, and 91%, respectively); also, we found a significantly increased expression of the 3 antigens in primary tumors and metastatic lymph nodes compared with normal mucosa and adenomas. MUC2 was expressed in 52% of both normal mucosa and CRC samples; this reactivity significantly decreased in metastatic lymph nodes (p<0.05). A multiple comparison analysis showed that MUC1 and sLex discriminated among 3 groups: normal, adenoma, and CRC tissues. The increase of sLex expression showed an association with recurrence, and survival analysis showed that a high sLex staining was significantly associated with a poor survival. By multivariate analysis MUC1 inmunoreactivity correlated positively and significantly with tumor size, while MUC2 expression showed the opposite correlation. Conclusions The correlation of sLex overexpression in primary tumors and metastatic lymph nodes, the discrimination among the normal, adenoma, and CRC groups based on sLex expression, as well as its association with recurrence and survival, all suggest a prognostic role of sLex in Argentinian CRC patients.


2015 ◽  
Vol 26 ◽  
pp. vi51
Author(s):  
R. Giampieri ◽  
M. Del Prete ◽  
L. Faloppi ◽  
M. Bianconi ◽  
K. Andrikou ◽  
...  

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