Bacterial Translocation from the Gut to the Distant Organs: An Overview

2017 ◽  
Vol 71 (Suppl. 1) ◽  
pp. 11-16 ◽  
Author(s):  
Ravinder Nagpal ◽  
Hariom Yadav

Background: The intestinal epithelial layer is the chief barricade between the luminal contents and the host. A healthy homeostatic intestinal barrier is pivotal for maintaining gastrointestinal health, which impacts the overall health as it safeguards the gut-blood axis and checks gut microbes including potential pathogens from entering into the circulation. Summary: Under healthy milieus, the intestinal barrier is generally very dynamic and effective, with luminal side being heavily infested with a wide variety of gut microbes while the basolateral side remains virtually sterile. However, certain conditions such as abnormal exposure to toxins, drugs, pathogens etc. or a state of hyper-inflammation due to disease conditions may weaken or destabilize the integrity of gut epithelia. A perturbed gut integrity and permeability (“leaky gut”) may lead to microbial (bacterial) translocation, and the eventual leakage of bacteria or their metabolites into the circulation can make the host susceptible to various types of diseases via inducing chronic or acute inflammatory response. Key Message: Given a close association with gut integrity, bacterial translocation and inflammatory responses have recently emerged as a clinically important research field and have unveiled novel aspects of gut microbial ecology and various gastrointestinal, metabolic, and lifestyle diseases. This review aims to describe the significance of a healthy gut barrier integrity and permeability, as well as the factors and consequences associated with a compromised gut barrier, while discussing briefly the dietary approaches including probiotics and prebiotics that could ameliorate gut health by restoring gut environment and barrier integrity, thereby preventing bacterial translocation.

2021 ◽  
Author(s):  
Narae Kim ◽  
Min jeong Gu ◽  
Yoon-Chul Kye ◽  
Young-Jun Ju ◽  
Rira Hong ◽  
...  

Abstract Bacteriophages have long been used as a potential alternative to antibiotics for livestock due to their ability to specifically kill ETEC, which are a major cause of diarrhea in piglets. However, the control of ETEC infection by phages within intestinal epithelial cells, and their relationship with host immune responses, remain poorly understood. In this study, we evaluated the effect of phage EK99P-1 against ETEC K99-infected IPEC-J2. Phage EK99P-1 prevented ETEC K99-induced barrier disruption by attenuating the increased permeability mediated by the loss of tight junction proteins such as ZO-1, occludin, and claudin-3. ETEC K99-induced inflammatory responses, such as IL-8 secretion, were decreased by treatment with phage EK99P-1. We used a IPEC-J2/PBMC Transwell co-culture system to investigate whether the modulation of barrier disruption and chemokine secretion by phage EK99P-1 in ETEC K99-infected IPEC-J2 would influence basolateral immune cells. The results showed that phage EK99P-1 reduced the mRNA expression of ETEC K99-induced pro-inflammatory cytokines, IL-1β and IL-8, from PBMC collected on the basolateral side. Together, these results suggest that phage EK99P-1 prevented ETEC K99-induced barrier dysfunction in IPEC-J2 and alleviated inflammation caused by ETEC K99 infection. Reinforcement of the intestinal barrier by phage EK99P-1 also modulates the immune cell inflammatory response.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 425-425
Author(s):  
Sunhye Lee ◽  
Michael Goodson ◽  
Wendie Vang ◽  
Karen Kalanetra ◽  
Daniela Barile ◽  
...  

Abstract Objectives 2’-fucosyllactose (2’-FL), the most predominant oligosaccharide found in human milk, acts as a prebiotic with beneficial effects on the host. The aim of this study was to determine the beneficial effect of 2’-FL on intestinal barrier integrity and metabolic functions in low-fat (LF)- and high-fat (HF)-fed mice. Methods Male C57/BL6 mice (n = 32, 8/group; 6 weeks old, JAX, CA) were counter-balanced into four weight-matched groups and fed either a low-fat (LF; 10% kcal fat with 7% kcal sucrose) or HF (45% kcal fat with 17% kcal sucrose) with or without supplementation of 2’-FL in the diet [10% (w/w), 8 weeks; LF/2’-FL or HF/2’-FL; BASF, Germany]. General phenotypes (body weight, energy intake, fat and lean mass), intestinal permeability (ex vivo in Ussing chambers), lipid profiles, and microbial metabolites were assessed. Results 2’-FL significantly attenuated the HF-induced increase in body fat mass with a trend to decrease body weight gain. 2’-FL significantly decreased intestinal permeability in LF-fed mice with a trend for a decrease in HF-fed mice. This was associated with a significant increase in interleukin-22, a cytokine known to have a protective role in intestinal barrier function. Visceral adipocyte size was significantly decreased by 2’-FL in both LF- and HF-fed mice. 2’-FL suppressed HF-induced upregulation of adipogenic transcription factors peroxisome proliferator-activated receptor gamma and sterol regulatory element binding protein-1c in the liver. Lastly, 2’-FL supplementation led to a significant elevation of lactic acid concentration in the cecum of HF-fed mice, which is known to be a product from beneficial microbes. Conclusions 2’-FL supplementation improved gut barrier integrity and lipid metabolism in mice with and without the metabolic challenge of HF feeding. These findings support the use of 2’-FL in the control of gut barrier function and metabolic homeostasis under normal and abnormal physiological conditions. Funding Sources BASF (Germany).


2021 ◽  
Vol 8 ◽  
Author(s):  
Lili Qi ◽  
Haiguang Mao ◽  
Xiaohui Lu ◽  
Tingting Shi ◽  
Jinbo Wang

Cinnamaldehyde is an aromatic aldehyde isolated from the essential oil of cinnamon. It has been proved to possess various bioactivities such as anti-inflammation, anti-bacteria and antihypertensive. Nevertheless, early weaning could lead to intestinal stress, causing a range of intestinal health problems. The aim of this study is to explore the effects of cinnamaldehyde on gut barrier integrity, inflammatory responses, and intestinal microbiome of early weaned rats. In this study, treatment with cinnamaldehyde (100 or 200 mg/kg bodyweight/day) for 2 weeks significantly promoted the production of mucins in the colonic epithelial tissue of rats. Cinnamaldehyde supplementation significantly upregulated the expression of Muc2, TFF3 and the tight junction proteins (ZO-1, claudin-1, and occludin). Hematoxylin and eosin staining results showed that colonic histopathological changes were recovered by cinnamaldehyde supplementation. The mRNA expression of IL-6 and TNF-α were significantly decreased in the cinnamaldehyde groups while the TNF-α protein levels were significantly decreased in the two cinnamaldehyde groups. Cinnamaldehyde treatment obviously attenuated the activation of NF-κB signaling pathway in rat colonic tissue and suppressed the production of inflammatory cytokines. Furthermore, cinnamaldehyde supplementation remodeled the gut microbiome structure, at the genus level, Akkermansia, Bacteroides, Clostridium III, Psychrobacter, Intestinimonas were increased, whereas those of Ruminococcus, Escherichia/Shigella were obviously decreased in the cinnamaldehyde treated groups. These findings indicated that cinnamaldehyde could effectively enhance intestinal barrier integrity, ameliorate inflammatory responses and remodel gut microbiome in early weaned rats.


2020 ◽  
Vol 2020 ◽  
pp. 1-20
Author(s):  
Hongming Su ◽  
Jianling Mo ◽  
Jingdan Ni ◽  
Huihui Ke ◽  
Tao Bao ◽  
...  

Accumulating evidence indicates that type 2 diabetes (T2D) is associated with intestinal barrier dysfunction and dysbiosis, implying the potential targets for T2D therapeutics. Andrographolide was reported to have several beneficial effects on diabetes and its associated complications. However, the protective role of andrographolide, as well as its underlying mechanism against T2D, remains elusive. Herein, we reported that andrographolide enhanced intestinal barrier integrity in LPS-induced Caco-2 cells as indicated by the improvement of cell monolayer barrier permeability and upregulation of tight junction protein expression. In addition, andrographolide alleviated LPS-induced oxidative stress by preventing ROS and superoxide anion radical overproduction and reversing glutathione depletion. In line with the in vitro results, andrographolide reduced metabolic endotoxemia and strengthened gut barrier integrity in db/db diabetic mice. We also found that andrographolide appeared to ameliorate glucose intolerance and insulin resistance and attenuated diabetes-associated redox disturbance and inflammation. Furthermore, our results indicated that andrographolide modified gut microbiota composition as indicated by elevated Bacteroidetes/Firmicutes ratio, enriched microbial species of Akkermansia muciniphila, and increased SCFAs level. Taken together, this study demonstrated that andrographolide exerted a glucose-lowering effect through strengthening intestinal barrier function and increasing the microbial species of A. muciniphila, which illuminates a plausible approach to prevent T2D by regulating gut barrier integrity and shaping intestinal microbiota composition.


2021 ◽  
Vol 12 ◽  
Author(s):  
Leila B. Giron ◽  
Harsh Dweep ◽  
Xiangfan Yin ◽  
Han Wang ◽  
Mohammad Damra ◽  
...  

A disruption of the crosstalk between the gut and the lung has been implicated as a driver of severity during respiratory-related diseases. Lung injury causes systemic inflammation, which disrupts gut barrier integrity, increasing the permeability to gut microbes and their products. This exacerbates inflammation, resulting in positive feedback. We aimed to test whether severe Coronavirus disease 2019 (COVID-19) is associated with markers of disrupted gut permeability. We applied a multi-omic systems biology approach to analyze plasma samples from COVID-19 patients with varying disease severity and SARS-CoV-2 negative controls. We investigated the potential links between plasma markers of gut barrier integrity, microbial translocation, systemic inflammation, metabolome, lipidome, and glycome, and COVID-19 severity. We found that severe COVID-19 is associated with high levels of markers of tight junction permeability and translocation of bacterial and fungal products into the blood. These markers of disrupted intestinal barrier integrity and microbial translocation correlate strongly with higher levels of markers of systemic inflammation and immune activation, lower levels of markers of intestinal function, disrupted plasma metabolome and glycome, and higher mortality rate. Our study highlights an underappreciated factor with significant clinical implications, disruption in gut functions, as a potential force that may contribute to COVID-19 severity.


Animals ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 1045 ◽  
Author(s):  
Silvia Clotilde Modina ◽  
Umberto Polito ◽  
Raffaella Rossi ◽  
Carlo Corino ◽  
Alessia Di Giancamillo

Weaning is very stressful for piglets and leads to alterations in the intestinal barrier, a reduction in nutrient absorption and a higher susceptibility to intestinal diseases with heavy economic losses. This review describes the structures involved in the intestinal barrier: the epithelial barrier, immune barrier and the enteric nervous system. Here, new insights into the interactions between feed components and the physiology and morphology of the epithelial barrier are highlighted. Dietary strategies focused on improving gut health are also described including amino acids, phytochemicals and organic acids.


2005 ◽  
Vol 73 (6) ◽  
pp. 3686-3692 ◽  
Author(s):  
Misha D. Luyer ◽  
Wim A. Buurman ◽  
M'hamed Hadfoune ◽  
Gea Speelmans ◽  
Jan Knol ◽  
...  

ABSTRACT Probiotic therapy modulates the composition of the intestinal flora and inhibits the inflammatory response. These properties may be of benefit in the preservation of gut barrier integrity after injury or stress. In this study, we examined the effect of two Lactobacillus strains selected for their pathogen exclusion properties on intestinal barrier integrity following hemorrhagic shock. Additionally, the responsiveness of the macrophage cell line RAW 264.7 to combined exposure to Lactobacillus DNA or oligodeoxynucleotides containing CpG motifs (CpG-ODN) and endotoxin was assessed by measuring tumor necrosis factor alpha (TNF-α) release. Rats were administered lactobacilli (5 × 109 CFU) or vehicle for 7 days and were subjected subsequently to hemorrhagic shock by withdrawal of 2.1 ml blood/100 g tissue. Levels of plasma endotoxin, bacterial translocation to distant organs, and filamentous actin (F-actin) in the ileum were determined 24 h later. Rats treated with Lactobacillus rhamnosus showed reduced levels of plasma endotoxin (8 ± 2 pg/ml versus 24 ± 4 pg/ml; P = 0.01), bacterial translocation (2 CFU/gram versus 369 CFU/gram; P < 0.01), and disruption of F-actin distribution following hemorrhagic shock compared with nontreated control rats. In contrast, pretreatment with Lactobacillus fermentum had no substantial effect on gut barrier integrity. Interestingly, DNA preparations from both lactobacilli reduced endotoxin-induced TNF-α release dose dependently, whereas CpG-ODN increased TNF-α release. In conclusion, the pathogen exclusion properties of both Lactobacillus strains and the reduction of endotoxin-induced inflammation by their DNA in vitro are not prerequisites for a beneficial effect of probiotic therapy on gut barrier function following hemorrhagic shock. Although pretreatment with Lactobacillus spp. may be useful to preserve gut barrier integrity following severe hypotension, a thorough assessment of specific strains seems to be essential.


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