Gut Damage Research Articles

Insecticidal and growth inhibitory activity of gut microbes isolated from adults of Spodoptera litura (Fab.)

BackgroundSpodoptera litura (Fab.) (Lepidoptera: Noctuidae) commonly known as tobacco caterpillar is a polyphagous pest that causes significant damage to many agricultural crops. The extensive use of chemical insecticides against S. litura has resulted in development of resistance. In order to find potential biocontrol agents, gut microbes were investigated for insecticidal potential. These microbes live in a diverse relationship with insects that may vary from beneficial to pathogenic.ResultsEnterococcus casseliflavus, Enterococcus mundtii, Serratia marcescens, Klebsiella pneumoniae, Pseudomonas paralactis and Pantoea brenneri were isolated from adults of S. litura. Screening of these microbial isolates for insecticidal potential against S. litura showed higher larval mortality due to K. pneumoniae and P. paralactis. These bacteria also negatively affected the development of insect along with significant decline in relative growth and consumption rate as well as efficiency of conversion of ingested and digested food of insect. The bacteria significantly decreased the reproductive potential of insect. Perturbations in the composition of gut microbiome and damage to gut epithelium were also observed that might be associated with decreased survival of this insect.ConclusionsOur study reveals the toxic effects of K. pneumoniae and P. paralactis on biology of S. litura. These bacteria may be used as potential candidates for developing ecofriendly strategies to manage this insect pest.

The combination of four main components in Xuebijing injection improved the preventive effects of Cyclosporin A in acute graft-versus-host disease mice by protecting intestinal microenvironment

Acute graft-versus-host disease (aGVHD) is a major life-threatening complication after Allogeneic Hematopoietic Stem Cell Transplant (allo-HSCT). Although a series of immunosuppressant agents are routinely used as the first-line prevention, the morbidity and mortality rate remains high in allo-HSCT recipients. Our previous work indicated that combining Xuebijing (XBJ) with Cyclosporin A (CSA) is superior to CSA alone in preventing aGVHD. However, it was not clear which compounds in XBJ may prevent aGVHD. Whether the effective compounds in XBJ can be safely combined with CSA to prevent GVHD remain to be evaluated. Here, we accessed whether the combination of four main components in XBJ (C0127) had the same efficacy as XBJ in preventing aGVHD. In addition, the effectiveness of a novel combination therapy (C0127 + CSA) on aGVHD prophylaxis was evaluated using 16 s rRNA sequencing and RNA sequencing approaches in vitro and in vivo. In aGVHD mice, C0127 enhanced the preventive effects of CSA including decreasing mortality, maintaining weight, reducing GVHD score and reducing the expression of IL-6 and TNF-α in serum. Fatal GVHD is a frequent consequence of intestinal tract damage. We found combining C0127 with CSA alleviated the gut damage and maintained the normal physiological function of intestine by H&E staining, intestinal permeability and short chain fatty acid (SCFA) assays. Next, 16 S sequencing analysis of feces showed the combination treatment maintained the intestinal microbial diversity, normalized the intestinal microorganism and prevented flora disorder by reducing the relative abundances of Escherichia coli and Enterococcus. Further, RNA-seq analysis of colonic epithelium revealed C0127 combined with CSA chiefly regulated chemokines and cytokines in IL-17 signaling pathway. The combination treatment reduced the expression of G-CSF and its effector STAT3 (an axis that aggravated gut inflammation and flora disorder) in gut epithelium on mRNA and protein level. These findings indicated that C0127 improved the prevention of CSA in aGVHD mice partially by protecting the gut from damage through normalizing G-CSF signaling, which regulates the intestinal microbiota and the integrity of the epithelial barrier.

Gut Dysfunction Markers Are Associated With Body Composition in Youth Living With Perinatally Acquired Human Immunodeficiency Virus.

The association between gut dysfunction and body fat composition in youth living with perinatal human immunodeficiency virus infection (YPHIV) has not been investigated. We included YPHIV aged 7-19 years from the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol with plasma available within 6 months of baseline whole-body dual energy x-ray absorptiometry (DXA) and HIV RNA ≤1000 copies/mL within 3 months of baseline DXA and a second DXA 2 years later. Plasma markers of bacterial translocation and gut barrier dysfunction (lipopolysaccharide binding protein [LBP], zonulin, and intestinal fatty acid binding protein [I-FABP]) were measured at baseline by enzyme-linked immunosorbent assay and log10 transformed. Adiposity outcomes included percentage total body, truncal, and extremity fat in kilograms from DXA. Linear regression models were fit using generalized estimating equations to assess associations of baseline gut markers (log10) on adiposity outcomes at baseline and 2 years, adjusted for demographic variables, current antiretroviral therapy exposure, and physical activity. Two hundred sixty-one youth were included; 128 had a second DXA. Median age at first DXA was 12 years (interquartile range, 10-14 years), 49% were female, and 69% were Black. After adjustment for potential confounders, log10 LBP was positively associated with percentage total body fat at baseline (β = 4.08, P < .01) and zonulin with adiposity measures at both time points (β = .94 to 6.50, P ≤ .01). I-FABP was inversely associated with percentage total body fat at baseline and year 2 (β = -2.36 and -3.01, respectively, P ≤ .02). Despite viral suppression, gut damage and the resultant bacterial translocation are associated with body composition measures in YPHIV.

Intestinal Disorder in Zebrafish Larvae (Danio rerio): The Protective Action of N-Palmitoylethanolamide-oxazoline.

IBD (Inflammatory Bowel Disease) is an inflammatory disease affecting the gastrointestinal tract that is common in both humans and veterinarians. Several studies have revealed the pharmacological properties of the oxazoline of palmitoylethanolamide (PEAOXA). Zebrafish larvae were exposed to sodium dextran sulphate (DSS) to induce enterocolitis and study the protective action of PEAOXA. After repetitive exposure with 0.25% DSS, larvae presented gut alteration with an increase in mucus production. Furthermore, DSS exposure induced an increase in the inflammatory pathway in the intestine, related to an increase in the Endoplasmic-reticulum (ER) stress genes. PEAOXA exposure at a concentration of 10 mg/L decreased the DSS-induced gut damage and mucus production, as well as being able to reduce the inflammatory and ER stress-related genes expression. In conclusion, our results demonstrate that the alterations induced by repeated exposure to DSS were counteracted by PEAOXA action that was able to inhibit the increase in inflammation and ER stress involved in the progression of enterocolitis.

Chronic Exposure to Cigarette Smoke Affects the Ileum and Colon of Guinea Pigs Differently. Relaxin (RLX-2, Serelaxin) Prevents Most Local Damage

Cigarette smoking (CS) is the cause of several organ and apparatus diseases. The effects of smoke in the gut are partially known. Accumulating evidence has shown a relationship between smoking and inflammatory bowel disease, prompting us to investigate the mechanisms of action of smoking in animal models. Despite the role played by neuropeptides in gut inflammation, there are no reports on their role in animal models of smoking exposure. The hormone relaxin has shown anti-inflammatory properties in the intestine, and it might represent a putative therapy to prevent gut damage caused by smoking. Presently, we investigate the effects of chronic smoke exposure on inflammation, mucosal secretion, and vasoactive intestinal peptide (VIP) and substance P (SP) expressions in the ileum and colon of guinea pigs. We also verify the ability of relaxin to counter the smoke-induced effects. Smoke impacted plasma carbon monoxide (CO). In the ileum, it induced inflammatory infiltrates, fibrosis, and acidic mucin production; reduced the blood vessel area; decreased c-kit-positive mast cells and VIP-positive neurons; and increased the SP-positive nerve fibers. In the colon, it reduced the blood vessel area and the goblet cell area and decreased c-kit-positive mast cells, VIP-positive neurons, and SP-positive nerve fibers. Relaxin prevented most of the smoking-induced changes in the ileum, while it was less effective in the colon. This study shows the diverse sensitivity to CS between the ileum and the colon and demonstrates that both VIP and SP are affected by smoking. The efficacy of relaxin proposes this hormone as a potential anti-inflammatory therapeutic to counteract gut damage in humans affected by inflammatory bowel diseases.

Camu Camu effects on microbial translocation and systemic immune activation in ART-treated people living with HIV: protocol of the single-arm non-randomised Camu Camu prebiotic pilot study (CIHR/CTN PT032)

IntroductionDespite the success of antiretroviral therapy (ART) in transforming HIV disease into a chronic infection, people living with HIV (PLWH) remain at risk for various non-AIDS inflammatory comorbidities. Risk of...

Ingested Polystyrene Microplastics as a Carrier of Heavy Metals (Cadmium or Silver): Uptake, Gut Damage, Oxidative Stress, and DNA Damage In Drosophila Larvae

Ingested Polystyrene Microplastics as a Carrier of Heavy Metals (Cadmium or Silver): Uptake, Gut Damage, Oxidative Stress, and DNA Damage In Drosophila Larvae

Stereotypic Expansion of T Regulatory and Th17 Cells during Infancy Is Disrupted by HIV Exposure and Gut Epithelial Damage.

Few studies have investigated immune cell ontogeny throughout the neonatal and early pediatric period, when there is often increased vulnerability to infections. In this study, we evaluated the dynamics of two critical T cell populations, T regulatory (Treg) cells and Th17 cells, over the first 36 wk of human life. First, we observed distinct CD4+ T cells phenotypes between cord blood and peripheral blood, collected within 12 h of birth, showing that cord blood is not a surrogate for newborn blood. Second, both Treg and Th17 cells expanded in a synchronous fashion over 36 wk of life. However, comparing infants exposed to HIV in utero, but remaining uninfected, with HIV-unexposed uninfected control infants, there was a lower frequency of peripheral blood Treg cells at birth, resulting in a delayed expansion, and then declining again at 36 wk. Focusing on birth events, we found that Treg cells coexpressing CCR4 and α4β7 inversely correlated with plasma concentrations of CCL17 (the ligand for CCR4) and intestinal fatty acid binding protein, IL-7, and CCL20. This was in contrast with Th17 cells, which showed a positive association with these plasma analytes. Thus, despite the stereotypic expansion of both cell subsets over the first few months of life, there was a disruption in the balance of Th17 to Treg cells at birth likely being a result of gut damage and homing of newborn Treg cells from the blood circulation to the gut.

Ellagic acid prevents gut damage via ameliorating microbe-associated intestinal lymphocyte imbalance.

Inflammatory bowel disease (IBD) pathogenesis involves a sustained microbial-mediated immune response following intestinal stress. Although administration of antibiotics can be an effective therapy, the misuse of antibiotics may risk unknown drug-resistant bacteria. In this study, piglets pretreated with ellagic acid (EA) and Ampicillin (AMP) for 21 days, and were injected intraperitoneally with paraquat (PQ) on 14 and 18 days. We found piglets lost most of their gut microbes in the AMP group, protected from subsequent intestinal damage caused by gut oxidative stress. Hence, we identified some gut microbes that may play a critical role in mediating cellular responses following cytokine stimulation in PQ-induced stress. EA preprocessing exhibited the same performance as AMP. Pretreatment of EA reduced Streptococcus abundance in the gut. Particularly, EA modulated intestinal lymphocyte distribution, reduced the frequency of CD79a+ cells, and alleviated the upward migration of CD3+ cells to the apex of the intestinal villi in the intestinal epithelium. Additionally, the intestinal immune response had been known associated closely with the abundance of Streptococcus in the gut. Thus, we concluded that EA has the potential to replace antibiotics to prevent microbial-mediated immune responses in the gut, and EA can be applied as a supplement candidate to alleviate the development of inflammation caused by intestinal stress.

Cinnamon(Cinnamomum japonicum) subcritical water extract suppresses gut damage induced by dextran sodium sulfate in mouse colitis model

• Clinical features and symptoms were improved in CSE-treated mice. • CSE inhibited MPO activity and reduced colonic inflammation. • CSE reduced pro-inflammatory reaction by inhibiting NF-κB inflammatory pathway. • CSE altered the gut microbiome and increases alpha-diversity in mice. Inflammatory bowel disease involves the breaking down of tight junctions and triggers leaky gut syndrome. In this study, we evaluated the effect of cinnamon subcritical water extract (CSE) on gut health improvement using a mouse colitis model induced by 5 % dextran sodium sulfate. The mice were treated with varying concentrations of CSE for 21 days and assessed. We examined histopathological changes, mRNA expression of cytokines and tight junction proteins, and alteration of the gut microbiome. CSE treatment improved clinical symptoms. Moreover, myeloperoxidase activity, interleukin (IL)-1β, IL-6, tumor necrosis factor-α protein, and mRNA expression were reduced in the CSE-treated groups. However, CSE increased the mRNA expression of tight junction proteins, such as ZO-1, occludin, mucin-1, mucin-2, and E-cadherin. In addition, CSE altered the microbiome to reduce inflammation. These results suggested that CSE could prevent dextran sodium sulfate sodium-induced colitis and disruption of the intestinal environment.

Co-formulant in a commercial fungicide product causes lethal and sub-lethal effects in bumble bees

Pollinators, particularly wild bees, are suffering declines across the globe, and pesticides are thought to be drivers of these declines. Research into, and regulation of pesticides has focused on the active ingredients, and their impact on bee health. In contrast, the additional components in pesticide formulations have been overlooked as potential threats. By testing an acute oral dose of the fungicide product Amistar, and equivalent doses of each individual co-formulant, we were able to measure the toxicity of the formulation and identify the ingredient responsible. We found that a co-formulant, alcohol ethoxylates, caused a range of damage to bumble bee health. Exposure to alcohol ethoxylates caused 30% mortality and a range of sublethal effects. Alcohol ethoxylates treated bees consumed half as much sucrose as negative control bees over the course of the experiment and lost weight. Alcohol ethoxylates treated bees had significant melanisation of their midguts, evidence of gut damage. We suggest that this gut damage explains the reduction in appetite, weight loss and mortality, with bees dying from energy depletion. Our results demonstrate that sublethal impacts of pesticide formulations need to be considered during regulatory consideration, and that co-formulants can be more toxic than active ingredients.

Effects of synthetic and natural microfibers on Daphnia magna-Are they dependent on microfiber type?

Microfibers, which are sourced from textiles and some products from the fishery industry, are the biggest contributors to microplastic pollution in aquatic ecosystems. In addition to these synthetic microfibers, naturally derived microfibers can also be found in aquatic environments. However, there are limited studies on the ecotoxicity of natural microfibers. To shed light on this topic, this study assessed and compared the toxicity of natural and synthetic microfibers on Daphnia magna, using lyocell, polyester (PET) and polypropylene (PP) microfibers. To evaluate the adverse effect of microfibers on D. magna, after effects including depuration, food intake, growth, mortality, and immobilization rate were continually observed for up to 96h after the initial 48h of exposure to the microfibers. Immobilization rate decreased in the following order: PP, PET, and lyocell. However, the depuration of microfibers in the lyocell and PET treatment groups was similar, with higher mortality rates than in the PP treatment group. Furthermore, despite the high rates of food intake following exposure, the lyocell and PET exposed groups exhibited growth inhibition during the same period. This growth inhibition corresponded with, and was likely due to, reductions in the length of gut microvilli, probably an expression of gut damage, which is believed to have reduced nutrient absorption in the affected individuals. Based on the results of this study, it was confirmed that even natural microfibers, and not just synthetic microfibers, can have adverse effects on aquatic organisms. This study confirmed not only the toxicity of microfibers, but also the consequences of their after effects. These results could be the basis for future research on the after effects of microplastics on aquatic organisms and provide directions for further microplastic ecotoxicity studies.

Dysbiosis of Gut Microbiota Promotes Hepatocellular Carcinoma Progression by Regulating the Immune Response.

Method This study included 74 Chinese male patients with HCC. They were divided into early (n = 19), intermediate (n = 37), and terminal (n = 18) groups, referred to as Barcelona Clinic Liver Cancer stage 0+A, B, and C+D, respectively. Paired fecal and plasma samples were collected. Microbial composition and profiles were analyzed by 16S rRNA gene sequencing. The levels of gut damage marker (regenerating islet-derived protein 3α (REG3α)) and microbial translocation markers (soluble CD14 (sCD14), lipopolysaccharide-binding protein (LBP), peptidoglycan recognition proteins (PGRPs)) were determined in plasma samples of patients by ELISA. Twenty plasma cytokine and chemokines were determined by Luminex. Results In early, intermediate, and terminal groups, the abundance of the Bifidobacteriaceae family decreased significantly (3.52%, 1.55%, and 0.56%, respectively, P = 0.003), while the abundance of the Enterococcaceae family increased significantly (1.6%, 2.9%, and 13.4%, respectively, P = 0.022). Levels of REG3α and sCD14 were markedly elevated only in the terminal group compared with the early (P = 0.025 and P = 0.048) and intermediate groups (P = 0.023 and P = 0.046). The level of LBP significantly increased in the intermediate (P = 0.035) and terminal (P = 0.025) groups compared with the early group. The PGRP levels were elevated only in the terminal group compared with the early group (P = 0.018). The ratio of Enterococcaceae to Bifidobacteriaceae was significantly associated with the levels of REG3α, LBP, sCD14, and PGRPs. With HCC progression, increased levels of inflammatory cytokines accompanied by a T cell-immunosuppressive response and microbial translocation were observed. Conclusion Gut microbiota compositional and functional shift, together with elevated gut damage and microbial translocation, may promote HCC development by stimulating inflammatory response and suppressing T cell response.

A field study on correlations between macroscopic gut health scoring, histological measurements and performance parameters in broilers

ABSTRACT Optimal intestinal health is a prerequisite for sustainable poultry production. Intestinal health can be evaluated by scoring macroscopic intestinal abnormalities and by histological measurements. The aim of this study was to evaluate correlations between macroscopic gut appearance scoring (GAS), coccidiosis lesion scoring, histological measurements and performance parameters in broilers under field conditions. Therefore, a cross-sectional study was performed on 50 broiler farms where birds were sampled at 28 days of age. The GAS was determined by scoring the absence or presence of 10 macroscopically visible parameters of the gastrointestinal tract, yielding a GAS between 0 and 10, with 0 meaning no gut abnormalities. On individual bird level, when birds had a GAS score of 6 or higher, significantly shorter villi were found in the duodenum. Also, CD3+ T-lymphocyte area percentage in the duodenal mucosa was significantly negatively correlated to villus length. On farm level, the average feed conversion ratio (FCR) was 1.59 ± 0.04 [1.52–1.73]. However, no correlations were found between the GAS at the age of 28 days and the prevalence of coccidiosis, nor did coccidiosis lesion scoring correlate with the FCR. Also, a higher GAS could not be associated with a higher FCR. In conclusion, on all farms a certain degree of macroscopic visible gut and coccidiosis lesions were present in birds of 28 days of age, while this did not correlate with the FCR. This suggests that broilers are able to cope with a certain level of gut damage before it influences the overall performance.

Sodium nitroprusside protects HFD induced gut dysfunction via activating AMPK\u03b1/SIRT1 signaling

BackgroundActivation of Adenosine 5′-monophosphate-activated protein kinase/Sirtuin1 (AMPK/SIRT1) exerts an effect in alleviating obesity and gut damage. Sodium nitroprusside (SNP), a nitric oxide (NO) donor, has been reported to activate AMPK. This study was to investigate the effect of SNP on HFD induced gut dysfunction and the mechanism.MethodsSNP was applied on lipopolysaccharide (LPS) stimulated Caco-2 cell monolayers which mimicked intestinal epithelial barrier dysfunction and HFD-fed mice which were complicated by gut dysfunction. Then AMPKα/SIRT1 pathway and gut barrier indicators were investigated.ResultsSNP rescued the loss of tight junction proteins ZO-1 and occludin, the inhibition of AMPKα/SIRT1 in LPS stimulated Caco-2 cell monolayers, and the effects were not shown when AMPKa1 was knocked-down by siRNA. SNP also alleviated HFD induced obesity and gut dysfunction in mice, as indicated by the decreasing of intestinal permeability, the increasing expression of ZO-1 and occludin, the decreasing levels of pro-inflammatory cytokine IL-6, and the repairing of gut microbiota dysbiosis. These effects were complicated by the increased colonic NO content and the activated AMPKα/SIRT1 signaling.ConclusionsThe results may imply that SNP, as a NO donor, alleviates HFD induced gut dysfunction probably by activating the AMPKα/SIRT1 signaling pathway.

Supplementation of Kiwifruit Polyphenol Extract Attenuates High Fat Diet Induced Intestinal Barrier Damage and Inflammation via Reshaping Gut Microbiome.

Background: Impaired intestinal integrity and barrier function is associated with various diseases, including inflammatory bowel disease and metabolic syndrome. In recent years, plant-derived polyphenols have attracted much attention on regulating intestinal barrier function. Kiwifruit was recorded as a traditional Chinese medicine which can treat gastrointestinal diseases, but the mechanism was still unclear. In this study we investigated the effects of kiwifruit polyphenol extracts (KPE) on high fat diet induced intestinal permeability and its possible mechanism.Results: Dietary supplementation of KPE with 50 or 100 mg/kg bw could inhibit the increase of intestinal permeability caused by HFD and promote the expression of tight junction protein (Claudin-1, Occludin and ZO-1). From microbial diversity and RT-PCR, KPE administration reshaping gut microbiome, the relative abundance of Lactobacillus and Bifidobacterium were increased, and the relative abundance of Clostridium and Desulfovibrionaceae were decreased. The changes in microbe may influence intestinal inflammatory status. Then the expression of TLRs and cytokines were detected. KPE supplementation showed anti-inflammatory effect, the expression of IL-10 was increased and the expression of TLR-2, TLR-4, TNF-α and IL-1β were decreased. Correlation analysis indicated that the expression of tight junction protein was negative correlation with TLR-2, TLR-4, TNF-α and IL-1β expression, but positively correlated with Bacteroidete, Bifidobacterium and IL-10 expression; the expression of Bacteroidete, Lactobacillusand and Bifidobacterium were negative correlation with TLR4, TNF-α, and IL-1β expression.Conclusion: KPE treatment relieve the intestinal damage caused by HFD, which was related to the regulation of Bacteroidete, Lactobacillusand, and Bifidobacterium expression and inhibit intestinal inflammation. KPE could be a functional component for preventing gut damage and its related disease.

Effects of extremely low-frequency electromagnetic field on different developmental stages of Drosophila melanogaster

Purpose The model biological organism Drosophila melanogaster has been utilized to assess the effect of extremely low-frequency electromagnetic field (ELF-EMF) on locomotion, longevity, developmental dynamics, cell viability and oxidative stress. Materials and method Developmental stages of Drosophila melanogaster (Oregon R strain) individually exposed to ELF-EMF (75 Hz, 550 µT) for 6 h once for acute exposure. For chronic exposure, complete life cycle of fly, that is, egg to adult fly was exposed to ELF-EMF for 6 h daily. The effect of exposure on their crawling and climbing ability, longevity, development dynamics, cellular damage and oxidative stress (generation of reactive oxygen species (ROS)) was evaluated. Results The crawling ability of larvae was significantly (p < .05) reduced on acute (third stage instar larvae) as well as chronic exposure (F0 and F1 larvae). When locomotion of flies was tested using climbing assay, no alteration was observed in their climbing ability under both acute and chronic exposure; however, when their speed of climbing was compared, a significant decrease in speed of F1 flies was observed (p = .0027) on chronic exposure. The survivability of flies was significantly affected under chronic and acute exposure (at third stage instar larvae). In case of acute exposure of the third stage instar larvae, although all the flies were eclosed by the 17th day, there was a significant decline in the number of flies (p = .007) in comparison to control. While in case of chronic exposure apart from low number of flies eclosed in comparison to control, there was delay in eclosion by one day (p = .0004). Using trypan blue assay, the internal gut damage of third stage instar larvae was observed. Under acute exposure condition at third stage instar larvae, 30% larvae has taken up trypan blue, while only 10% larvae from acute exposure at adult stage. On chronic exposure, 50% larvae of the F1 generation have taken up trypan blue. On evaluation of oxidative stress, there is a significant rise in ROS in case of acute exposure at third stage instar larvae (p = .0004), adult fly stage (p = .0004) and chronic exposure (p = .0001). Conclusion ELF-EMF has maximum effects on acute exposure of third stage instar larvae and chronic exposure (egg to adult fly stage). These results suggest that electromagnetic radiations, though, have become indispensible part of our lives but they plausibly affect our health.

Circulating intestinal fatty acid binding protein and intestinal toxicity in russell’s viper envenomation

Objective Abdominal pain is known to be an early clinical predictor of severe systemic Russell’s viper (RV) envenomation and is often associated with the later development of coagulopathy and neurotoxicity. The mechanism of abdominal pain is unknown, but we postulated it might be due to intestinal microvascular endothelial gut damage. Gut-toxicity can be detected using the novel biomarker Intestinal Fatty Acid Binding Protein (IFABP). We also wanted to explore the mechanisms and consequences of this toxicity by measuring procalcitonin as a specific marker of sepsis triggered by bacterial endotoxin, and serum cystatin-C (CysC) as a measure of acute kidney injury. We hypothesised that severe gut-injury might lead to gut-barrier failure, translocation of gastrointestinal microorganisms, associated sepsis and systemic inflammatory response syndrome (SIRS), with a possible exacerbation of snake-bite severity, including acute kidney injury that was previously attributed to direct venom effects. Methods Serial plasma samples previously collected from 16 RV envenomations with abdominal pain, 15 RV envenomations without abdominal pain and 25 healthy controls were assayed for IFABP. A subgroup of these RV envenomations were assayed for procalcitonin (n = 24) and serum CysC (n = 11). Results The median peak IFABP for RV envenomations was much higher than healthy controls [3703.0 pg/mL (IQR 2250.1–13702.0 pg/mL) vs. 270.1 pg/mL (IQR 153.5–558.0 pg/mL) (p < 0.001)]. There was no difference in those with and without abdominal pain [3801.4 pg/mL (IQR 2080.5–22446.3 pg/mL) vs. 3696.6 pg/mL (IQR 2280.3–4664.7 pg/mL) (p = 1.0)]. Peak procalcitonin levels were elevated in envenomed patients 30.1 ng/ml (IQR: 13.1–59.7 ng/ml) with a level >2ng/mL indicative of severe sepsis] and also correlated with peak IFABP (r = 0.55, p = 0.006, n = 24). Peak serum CysC was also elevated and also correlated with IFABP (r = 0.71, p = 0.037, n = 9). Conclusion IFABP is significantly elevated indicating enterocyte damage occurs in RV envenomation. IFABP correlated with markers of sepsis (procalcitonin) and acute kidney injury (serum CysC) suggesting that enterocyte damage resulting in translocation of microbial associated molecular patterns (MAMPs) contributes to RV envenomation associated SIRS and sepsis.

Microbiota modulate Doxorubicin induced cardiotoxicity

Chemotherapy has several adverse effects to patients, some of which are life-threatening. We hypothesized that Doxorubicin induced microbiome imbalance and intestinal damage may contribute to Doxorubicin induced cardiac dysfunction. Male adult (2–3 months) C57BL/6 mice were administered 3 mg/kg, 5 mg/kg, 7.5 mg/kg,15 mg/kg, 20 mg/kg doses of Doxorubicin. Echocardiography was performed at 7 and 14 days after Doxorubicin administration. 16S rRNA amplicon sequencing was used to characterize microbiome changes. Fecal microbiota transplantation (FMT) was performed to evaluate the role of the microbiota on Doxorubicin induced cardiac dysfunction.Doxorubicin dose dependently increases mortality rate and induces cardiac dysfunction. 5 mg/kg-Doxorubicin significantly induces decreased left ventricular ejection fraction (LVEF) and fraction shortening (FS) as well as increased cardiac fibrosis, inflammation and oxidative stress respond without increasing mortality. 5 mg/kg-Doxorubicin induces significant decreased colorectum length, increased loss of goblet cells, numbers of ulcers and infiltration of lymphocyte clusters and decreased tight junction protein ZO-1, as well as increased plasma endotoxin level measured by ELISA assay. 16S rRNA microbiota analysis shows that Doxorubicin-induced microbiota dysbiosis with decreased community richness compared with normal control mice. FMT to Doxorubicin-5 mg treated mice significantly improved cardiac function by increasing LVEF and FS as well as decreased perivascular and interstitial fibrosis; increased colorectum length, decreased the loss of goblet cells,infiltration of lymphocyte clusters,the number of ulcers and plasma endotoxin level; improved microbiota composition, function and diversity with increased abundance of Alloprevotella, Prevotellaceae_UCG−001 and Rikenellaceae_RC9_gut_group. We find that normal fecal transplantation improves cardiac function, decreases gut damage and alter microbiota composition induced by Doxorubicin. The microbiota appears to contribute to heart-gut interaction.

Therapeutic implications of SARS-CoV-2 dysregulation of the gut-brain-lung axis.

The emergence and rapid spread of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused over 180 million confirmed cases resulting in over 4 million deaths worldwide with no clear end in sight for the coronavirus disease 19 (COVID-19) pandemic. Most SARS-CoV-2 exposed individuals experience mild to moderate symptoms, including fever, cough, fatigue, and loss of smell and taste. However, many individuals develop pneumonia, acute respiratory distress syndrome, septic shock, and multiorgan dysfunction. In addition to these primarily respiratory symptoms, SARS-CoV-2 can also infiltrate the central nervous system, which may damage the blood-brain barrier and the neuron's synapses. Resultant inflammation and neurodegeneration in the brain stem can further prevent efferent signaling to cranial nerves, leading to the loss of anti-inflammatory signaling and normal respiratory and gastrointestinal functions. Additionally, SARS-CoV-2 can infect enterocytes resulting in gut damage followed by microbial dysbiosis and translocation of bacteria and their byproducts across the damaged epithelial barrier. As a result, this exacerbates pro-inflammatory responses both locally and systemically, resulting in impaired clinical outcomes. Recent evidence has highlighted the complex interactions that mutually modulate respiratory, neurological, and gastrointestinal function. In this review, we discuss the ways SARS-CoV-2 potentially disrupts the gut-brain-lung axis. We further highlight targeting specific responses to SARS-CoV-2 for the development of novel, urgently needed therapeutic interventions. Finally, we propose a prospective related to the individuals from Low- and Middle-Income countries. Here, the underlying propensity for heightened gut damage/microbial translocation is likely to result in worse clinical outcomes during this COVID-19 pandemic.