Astragalus membranaceus Polysaccharide Regulates Small Intestinal Microbes and Activates IL-22 Signal Pathway to Promote Intestinal Stem Cell Regeneration in Aging Mice.

Aging can cause degenerative changes in multiple tissues and organs. Gastrointestinal diseases and dysfunctions are common in the elderly population. In this study, we investigated the effects of Astragalus membranaceus polysaccharide (APS) and Astragalus membranaceus ethanol extract (AEE) on age-related intestinal dysfunction and gut microbiota dysbiosis in naturally aging mice. The energy expenditure and physical activity of 23-month-old C57BL6/J mice were recorded using a metabolic cage system. Pathological changes in the intestine were evaluated using Alcian blue staining. The protein levels of leucine-rich repeats containing G protein-coupled receptor 5 (Lgr5) and Stat3 in the small intestine were determined using immunohistochemistry. The intestinal cell migration distance was assessed using bromodeoxyuridine (BrdU) immunofluorescence staining. The gene transcription levels of intestinal stem cell (ISC) markers and ISC-related signaling pathways were detected using quantitative real-time PCR (qRT-PCR). Microbiota analysis based on 16S rDNA was performed to evaluate the composition of the gut microbiota. APS and AEE improved a series of aging phenotypes in female but not in male aging mice. APS and AEE ameliorate intestinal dysfunction and histopathological changes in aging mice. APS had a more significant anti-aging effect than AEE, particularly on intestinal dysfunction. APS promotes ISC regeneration by activating the IL-22 signaling pathway. Cohousing (CH) experiments further confirmed that APS induced the IL-22 signaling pathway by increasing the abundance of Lactobacillus, thereby promoting the regeneration of ISCs. Our results show that APS may serve as a promising agent for improving age-related intestinal dysfunction.

Polystyrene microplastics with absorbed nonylphenol induce intestinal dysfunction in human Caco-2 cells.

Due to the massive production and use of plastic, the chronic and evolving exposure to microplastics in our daily lives is omnipresent. Nonylphenol (NP), a persistent organic pollutant, may change toxicity when it co-exists with microplastics. In this study, polystyrene microplastics (PS-MPs), either alone or with pre-absorbed NP, generated oxidative stress and inflammatory lesions to Caco-2 cells, as well as affecting proliferation via the MAPK signaling pathway and causing apoptosis. Damage to cell membrane integrity and intestinal barrier (marked by lower transepithelial electric resistance, greater bypass transport, and tight junction structural changes) leads to enhanced internalization risk of PS-MPs. Some important intestinal functions including nutrient absorption and xenobiotic protection were also harmed. It is worth noting that the exposure of PS-MPs with a diameter of 0.1 µm improved intestinal functions quickly but acted as a chemosensitizer for a long time, inhibiting cell perception of other toxic substances and making the cells more vulnerable.

[The complex effect of polyphenols on the gut microbiota and triggers of neurodegeneration in Parkinson's disease]. / Kompleksnoe vliyanie polifenolov na mikrobiom kishechnika i puskovye mekhanizmy neirodegeneratsii pri bolezni Parkinsona.

Intestinal dysfunction and microbiome changes are actively discussed in the modern literature as the most important link in the development of neurodegenerative changes in Parkinson's disease. The article discusses the pathogenetic chain «microbiome- intestine-brain¼, as well as factors that affect the development of intestinal dysbiosis. A promising direction for influencing microflora and inflammatory changes in the intestine is the use of polyphenols, primarily curcumin. The review of experimental, laboratory, clinical research proving the pleiotropic effect of curcumin, including its antioxidant, anti-inflammatory, neuroprotective effects, realized both through peripheral and central mechanisms is presented.

Systemic mapping of organ plasma extravasation at multiple stages of chronic heart failure.

Introduction: Chronic Heart failure (CHF) is a highly prevalent disease that leads to significant morbidity and mortality. Diffuse vasculopathy is a commonmorbidity associated with CHF. Increased vascular permeability leading to plasma extravasation (PEx) occurs in surrounding tissues following endothelial dysfunction. Such micro- and macrovascular complications develop over time and lead to edema, inflammation, and multi-organ dysfunction in CHF. However, a systemic examination of PEx in vital organs among different time windows of CHF has never been performed. In the present study, we investigated time-dependent PEx in several major visceral organs including heart, lung, liver, spleen, kidney, duodenum, ileum, cecum, and pancreas between sham-operated and CHF rats induced by myocardial infarction (MI). Methods: Plasma extravasation was determined by colorimetric evaluation of Evans Blue (EB) concentrations at 3 days, ∼10 weeks and 4 months following MI. Results: Data show that cardiac PEx was initially high at day 3 post MI and then gradually decreased but remained at a moderately high level at ∼10 weeks and 4 months post MI. Lung PEx began at day 3 and remained significantly elevated at both ∼10 weeks and 4 months post MI. Spleen PExwas significantly increased at ∼10 weeks and 4 months but not on day 3 post MI. Liver PEx occurred early at day 3 and remain significantly increased at ∼10 weeks and 4 months post MI. For the gastrointestinal (GI) organs including duodenum, ileum and cecum, there was a general trend that PEx level gradually increased following MI and reached statistical significance at either 10 weeks or 4 months post MI. Similar to GI PEx, renal PEx was significantly elevated at 4 months post MI. Discussion: In summary, we found that MI generally incites a timedependent PEx of multiple visceral organs. However, the PEx time window for individual organs in response to the MI challenge was different, suggesting that different mechanisms are involved in the pathogenesis of PEx in these vital organs during the development of CHF.

The Effect of Maternal Probiotic or Synbiotic Supplementation on Sow and Offspring Gastrointestinal Microbiota, Health, and Performance.

The increasing prevalence of antimicrobial-resistant pathogens has prompted the reduction in antibiotic and antimicrobial use in commercial pig production. This has led to increased research efforts to identify alternative dietary interventions to support the health and development of the pig. The crucial role of the GIT microbiota in animal health and performance is becoming increasingly evident. Hence, promoting an improved GIT microbiota, particularly the pioneer microbiota in the young pig, is a fundamental focus. Recent research has indicated that the sow's GIT microbiota is a significant contributor to the development of the offspring's microbiota. Thus, dietary manipulation of the sow's microbiota with probiotics or synbiotics, before farrowing and during lactation, is a compelling area of exploration. This review aims to identify the potential health benefits of maternal probiotic or synbiotic supplementation to both the sow and her offspring and to explore their possible modes of action. Finally, the results of maternal sow probiotic and synbiotic supplementation studies are collated and summarized. Maternal probiotic or synbiotic supplementation offers an effective strategy to modulate the sow's microbiota and thereby enhance the formation of a health-promoting pioneer microbiota in the offspring. In addition, this strategy can potentially reduce oxidative stress and inflammation in the sow and her offspring, enhance the immune potential of the milk, the immune system development in the offspring, and the sow's feed intake during lactation. Although many studies have used probiotics in the maternal sow diet, the most effective probiotic or probiotic blends remain unclear. To this extent, further direct comparative investigations using different probiotics are warranted to advance the current understanding in this area. Moreover, the number of investigations supplementing synbiotics in the maternal sow diet is limited and is an area where further exploration is warranted.

The Effect of Prebiotic Supplements on the Gastrointestinal Microbiota and Associated Health Parameters in Pigs.

Establishing a balanced and diverse microbiota in the GIT of pigs is crucial for optimizing health and performance throughout the production cycle. The post-weaning period is a critical phase, as it is often associated with dysbiosis, intestinal dysfunction and poor performance. Traditionally, intestinal dysfunctions associated with weaning have been alleviated using antibiotics and/or antimicrobials. However, increasing concerns regarding the prevalence of antimicrobial-resistant bacteria has prompted an industry-wide drive towards identifying natural sustainable dietary alternatives. Modulating the microbiota through dietary intervention can improve animal health by increasing the production of health-promoting metabolites associated with the improved microbiota, while limiting the establishment and proliferation of pathogenic bacteria. Prebiotics are a class of bioactive compounds that resist digestion by gastrointestinal enzymes, but which can still be utilized by beneficial microbes within the GIT. Prebiotics are a substrate for these beneficial microbes and therefore enhance their proliferation and abundance, leading to the increased production of health-promoting metabolites and suppression of pathogenic proliferation in the GIT. There are a vast range of prebiotics, including carbohydrates such as non-digestible oligosaccharides, beta-glucans, resistant starch, and inulin. Furthermore, the definition of a prebiotic has recently expanded to include novel prebiotics such as peptides and amino acids. A novel class of -biotics, referred to as "stimbiotics", was recently suggested. This bioactive group has microbiota-modulating capabilities and promotes increases in short-chain fatty acid (SCFA) production in a disproportionally greater manner than if they were merely substrates for bacterial fermentation. The aim of this review is to characterize the different prebiotics, detail the current understating of stimbiotics, and outline how supplementation to pigs at different stages of development and production can potentially modulate the GIT microbiota and subsequently improve the health and performance of animals.

Emodin protects against intestinal dysfunction and enhances survival in rat model of septic peritonitis through anti-inflammatory actions.

BACKGROUND: Sepsis is a significant contributor to organ function damage or failure that results in intestinal dysfunction. Emodin (Emo) has received much attention for its notable anti-inflammatory and antibacterial properties. We aimed to explore the function of Emo on sepsis. METHODS: Sprague Dawley (SD) rats were pretreated with 20 or 40 mg/kg of Emo, followed by using cecal ligation and perforation to establish sepsis models. Hereafter, blood glucose levels, biochemical parameters, and inflammatory cytokines were measured. Additionally, ileal myeloperoxidase (MPO) activity was also measured. Diamine oxidase (DAO) level in plasma, fluorescein isothiocyanate-dextran 40 (FD-40) level in serum, bacteria number in blood and peritoneal fluid, histopathological changes of ileum, and tight junction (TJ) protein expressions in ileum were tested to evaluate the barrier function. Furthermore, CD4+ and CD8+ T cells' percentages were evaluated by flow cytometry. Finally, rats' survival rate was calculated as live rats divided by the total number of rats. RESULTS: Emo pretreatment not only decreased blood glucose level, but also downregulated triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine (SCr), blood urea nitrogen (BUN) contents for sepsis rats, especially for the high dose of Emo (p < .05). Furthermore, Emo inhibited MPO activity and inflammatory factor release (p < .05). Crucially, after Emo administration, the barrier function of ileum was enhanced, evidenced by the reduced DAO, FD-40 levels, decreased bacteria number, alleviated pathological damage in ileum and increased TJ protein expressions (p < .05). Rats treated with Emo exhibited increased percentages of CD8+ and CD4+ T cells (p < .05), as well as an improved survival rate. CONCLUSION: Emo exhibited a remarkable ability to attenuate sepsis by restoring intestinal dysfunction and improving survival rates, and the mechanism was closely related to anti-inflammatory properties, which provided new solid evidence for the use of Emo in treating sepsis.

6PPD and its metabolite 6PPDQ induce different developmental toxicities and phenotypes in embryonic zebrafish.

The automobile tire antioxidant N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and its quinone metabolite 6PPDQ have recently received much attention for their acute aquatic toxicity. The present study investigated the mechanistic developmental toxicity of 6PPD and 6PPDQ in embryonic zebrafish. Neither compound induced significant mortality but significantly decreased spontaneous embryo movement and heart rate. Both compounds induced malformations with different phenotypes; the 6PPD-exposed larvae manifested a myopia-like phenotype with a convex eyeball and fusion vessels, while the 6PPDQ-exposed embryonic zebrafish manifested enlarged intestine and blood-coagulated gut, activated neutrophils, and overexpressed enteric neurons. mRNA-Seq and quantitative real-time PCR assays showed that 6PPD- and 6PPDQ-induced distinct differential gene expression aligned with their toxic phenotype. 6PPD activated the retinoic acid metabolic gene cyp26a, but 6PPDQ activated adaptive cellular response to xenobiotics gene cyp1a. 6PPD suppressed the gene expression of the eye involved in retinoic acid metabolism, phototransduction, photoreceptor function and visual perception. In contrast, 6PPDQ perturbed genes involved in inward rectifier K+ and voltage-gated ion channels activities, K+ import across the plasma membrane, iron ion binding, and intestinal immune network for IgA production. The current study advances the present understanding the reason of why many fish species are so adversely impacted by 6PPD and 6PPDQ.

Lactulose regulates gut microbiota dysbiosis and promotes short-chain fatty acids production in acute pancreatitis patients with intestinal dysfunction.

BACKGROUND: Intestinal dysfunction is one of the common complications in the early stage of acute pancreatitis (AP), which often associates with bad outcome. Lactulose, as a prebiotic, has been widely used to improve gut health, yet its effect on AP is unclear. METHODS: This was a prospective, randomized trial of moderate severe AP patients complicated with intestinal dysfunction. A total of 73 participants were randomly assigned to receive either lactulose or Chinese herb rhubarb for 1 week. The primary efficacy endpoint was the recovery of intestinal function. The serum levels of inflammatory cytokines and gut barrier indexes were examined. The fecal samples from patients before and after treatment were collected. 16 S rRNA gene sequencing analysis was performed to explore the composition of gut microbiota and the amount of short-chain fatty acids (SCFAs) were detected by gas chromatography-mass spectrometry (GC-MS). RESULTS: The intestinal dysfunction was prominently improved after 7 days of treatment with either lactulose or rhubarb. The serum levels of cytokines and gut permeability index were decreased after treatment, with stronger down-regulated degree in lactulose group than rhubarb. The potential beneficial genus Bifidobacterium was enriched in lactulose group, while pathogenic bacteria including Escherichia-Shigella and Neisseria were abundant in rhubarb group. Of note, the level of SCFAs was remarkably increased after treatment, with higher amount in lactulose group than rhubarb group. CONCLUSIONS: Lactulose could not only restore intestinal function but also regulate gut microbiota and promote the production of SCFAs.

[The neuro-urological expert opinion in statutory accident insurance : Consensual recommendations for diagnostics and for the assessment of reduction of earning capacity]. / Das neurourologische Gutachten in der gesetzlichen Unfallversicherung : Konsentierte Empfehlungen zur Diagnostik und zur Bewertung der Minderung der Erwerbsfähigkeit.

BACKGROUND: Previous assessment guidelines from standard sources for urologic expert opinions show considerable differences in the recommended percentages for the assessment of reduction of earning capacity (MdE) for accident sequelae in the neuro-urological specialty. OBJECTIVES: To develop a "revised and standardized version of the MdE assessments of neuro-urological accident sequelae (in tabular form) as a guideline/manual" for expert opinions in the legal area of the German and Austrian Statutory Accident Insurance ( www.dguv.de , www.auva.at ). MATERIALS AND METHODS: A working group of neuro-urologists from spinal cord injury centers of different BG ("Berufsgenossenschaft") clinics was formed within the working group Neuro-Urology of DMGP (German-speaking Medical Society for Paraplegiology; www.dmgp.de ). Between January 2017 and September 2022, a total of 7 working meetings and 2 video conferences were held. The consensus of the developed documents was reached by formal consensus finding in a nominal group process and in a final consensus conference. RESULTS: The necessary bases for a targeted, legally sound diagnosis of accident consequences in the neuro-urological field were elaborated and, based on the experience of many years of expert opinion activity, a "matrix" for a uniform, graduated assessment of the level of reduction of earning capacity in the (neuro-)urological field in the case of confirmed neuro-urological accident consequences was created. CONCLUSION: In the interest of equal treatment of all insured persons, it is of great importance to make a uniform and comprehensible assessment of the amount of the MdE on the basis of "table values" that reflect the available empirical values.

Escin alleviates stress-induced intestinal dysfunction to protect brain injury by regulating the gut-brain axis in ischemic stroke rats.

Hyperactivity of HPA axis results in intestinal dysfunction, which may play a role in brain injury caused by ischemic stroke (IS). Escin shows a neuroprotective effect but it may not penetrate blood brain barrier (BBB). Previous work in our laboratory showed that escin ameliorated intestinal injury in animals. The aim of this study is to investigate whether escin attenuates brain injury by improving intestinal dysfunction in middle cerebral artery occlusion (MCAO) rats, to mimic IS. MCAO rats and lipopolysaccharides (LPS)-induced Caco-2 cells were used to evaluate the effects of escin in vivo and in vitro. The results showed that escin could not penetrate BBB but reduced brain infarct volume, improved neurological function, inhibited neuroinflammation, ameliorated intestinal dysfunction and tissue integrity by increasing the expression of the tight junction protein in vivo and in vitro. Escin reduced the increased corticosterone and endotoxin level in blood of MCAO rats, regulated GR/p38 MAPK/NF-κB signaling pathway in ileal tissue and LPS/TLR4/NF-κB signaling pathway in ischemic brain tissue. These findings suggest that escin could attenuate ischemic brain injury by improving intestinal dysfunction, and it may be a promising way to protect brain injury by protecting intestine, instead of targeting the brain directly after IS.

Intestinal permeability evaluation in patients with chronic Chagas heart failure.

AIMS: We analysed intestinal permeability in patients with chronic Chagas cardiomyopathy (CCC) and evaluated its association with clinical manifestations, haemodynamic parameters measured by echocardiogram, and disease outcome. Intestinal permeability was compared between CCC patients and a group of healthy controls. BACKGROUND: Intestinal dysfunction may contribute to a more severe disease presentation with worse outcome in patients with CCC and heart failure. METHODS: Fifty patients with CCC and left ventricular ejection fraction (LVEF) of less than 55% were prospectively selected and followed for a mean period of 18 ± 8 months. A group of 27 healthy volunteers were also investigated. One patient was excluded from the analysis since he died before completing the intestinal permeability test. Intestinal permeability was evaluated with the sugar probe drink test. It consists in the urinary recovery of previously ingested sugar probes: mannitol, a monosaccharide, and lactulose, a disaccharide. RESULTS: Patient's mean age was 53.4 ± 10.4 years, and 31(63%) were male. Differential urinary excretion of lactulose/mannitol ratio did not differ significantly between healthy controls and CCC patients, regardless of clinical signs of venous congestion, haemodynamic parameters, and severity of presentation and outcome. CONCLUSIONS: The present study could not show a disturbance of the intestinal barrier in CCC patients with LVEF <55%, measured by lactulose/mannitol urinary excretion ratio. Further investigations are needed to verify if in patients with LVEF <40% intestinal permeability is increased.

Sestrin2 suppresses ferroptosis to alleviate septic intestinal inflammation and barrier dysfunction.

OBJECTIVE: Alterations in intestinal function play a crucial role in the pathogenesis of sepsis, and the repair of the intestinal barrier is a potential strategy for the treatment of sepsis. Sestrin2 (SESN2), a highly conserved stress-responsive protein, can be induced in response to stress. AIM: This paper aimed to explore the role and mechanism of SESN2 in septic intestinal dysfunction. METHODS: Blood samples were collected from patients with septic intestinal dysfunction, and Caco-2 cells were subjected to lipopolysaccharide (LPS) to construct in vitro models. The expression level of SESN2 was determined in the blood samples and cells. The impacts of SESN2 overexpression on cell inflammation, oxidative stress, barrier integrity, and MAPK/Nrf2 signaling were evaluated. To determine the mediated role of MAPK signaling and ferroptosis, AMPK inhibitor (Compound C) and ferroptosis inducer (erastin) were separately used to treat cells, and the influences on the above aspects in cells were assessed. RESULTS: The expression level of SESN2 was down-regulated in patients with septic intestinal dysfunction and LPS-induced cells. SESN2 overexpression was found to suppress cell inflammation and oxidative stress, maintain barrier integrity, and activate AMPK/Nrf2 signaling. Following the AMPK signaling was inhibited or the ferroptosis was triggered, the effects of SESN2 overexpression on the cells were both reversed. CONCLUSION: Reduced SESN2 contributed to inflammatory response and barrier dysfunction in septic intestinal dysfunction by promoting ferroptosis via activating the AMPK/Nrf2 signaling pathway.

Preoperative bowel preparation promotes intestinal functional recovery after esophagectomy.

Background: Patients are prone to intestinal dysfunction after esophagectomy. The value of preoperative bowel preparation before esophagectomy is controversial. There is a lack of evidence as to whether preoperative bowel preparation can help patients improve bowel function and shorten the recovery time of bowel function. Objectives: The objectives of this study were to explore whether preoperative bowel preparation can promote the recovery of intestinal function after esophagectomy. Methods: We analysed 139 patients who underwent elective radical esophagectomy in the Department of Thoracic Surgery at the Second Affiliated Hospital of Xi'an Jiaotong University from May 2016 to December 2018. The enrolled patients were divided into the study group (bowel preparation group) and the control group (no bowel preparation group) of 71 cases and 68 cases. Patients in the study group were given dissolved polyethylene glycol electrolyte powder and a cleansing enema the day before surgery. Patients in the control group were neither given polyethylene glycol electrolyte powder nor cleansing enemas before surgery. The postoperative recovery of the two groups were compared. Results: Postoperative bed rest time, bowel function recovery time and the time of first flatus and defecation after surgery were significantly shorter in patients with bowel preparation than in those without bowel preparation, and the differences were statistically significant. (P=0.038, P<0.001, P<0.001, P<0.001; respectively). Conclusions: Preoperative bowel preparation can promote the recovery of patients with esophageal cancer, especially the recovery of bowel function, which can reduce the pain caused by abdominal distension and improve the quality of life of patients.

Pathogenetic justification of digestive tract dysfunction correction to reduce the risk of ventricular extrasystoles after coronary bypass grafting.

Introduction: In heart pathology, abdominal pathology is often detected, but due attention has not been paid to this issue, and algorithms for predicting, preventing, and correcting the coefficient of endothelial dysfunction (CED) after coronary artery bypass grafting (CABG) with the use of artificial circulation (AC) have not been developed. Aim: To substantiate the pathogenetic expediency of correction of postoperative intestinal paresis after coronary artery bypass grafting for the prevention of functional cardiac complications. Material and methods: 147 men were divided into 2 groups. Statistical processing of the obtained data was performed using Windows Microsoft Excel software and parametric methods of variational statistics, and the reliability of differences was determined using Student's formula and table. Results: It was found that in group II, after coronary artery bypass grafting, the clinical symptoms of intestinal dysfunction were significantly less (p = 0.019), and the recovery of defecation was significantly faster (p = 0.033) than in group I. After coronary artery bypass grafting, the frequency of high-grade extrasystoles in group II was significantly lower than in group I (p = 0.033). Conclusions: The application of the digestive tract dysfunction correction program is pathogenetically justified because it provides a reduction in the frequency of intestinal paresis and hence a reduction in the frequency of development of ventricular extrasystoles of high gradations after coronary artery bypass grafting.

Treatment of postoperative intestinal dysfunction of hirschsprung's disease based on the principle of "anorectal balance".

Purpose: Radical surgery is the most effective treatment for Hirschsprung's disease. However, some children still have symptoms of intestinal dysfunction such as constipation, abdominal distension, and recurrent enterocolitis after operation. The purpose of this study was to evaluate treatment outcomes of postoperative intestinal dysfunction in children with Hirschsprung's disease by using the principle of "anorectal balance". Methods: The clinical data of postoperative intestinal dysfunction in children with Hirschsprung's disease in the single treatment group from July 2019 to July 2021 were retrospectively analyzed. All the enrolled children underwent botulinum toxin injection (2.5 U/kg); 3 to 6 months later, the injection was performed again; the children who had received more than two botulinum toxin injections underwent the internal sphincter myectomy. Anorectal manometry was performed routinely after operation, and abdominal distension and defecation were recorded. Results: A total of thirty children with postoperative intestinal dysfunction underwent radical surgery for Hirschsprung's disease were included in this study. Symptoms of constipation, abdominal distension and enterocolitis were improved after botulinum toxin injections in most children compared to before surgery (P < 0.01). After re-injection of botulinum toxin in twelve children, the frequency of defecation increased, the anal resting pressure decreased, and the clinical symptoms were relieved again (P < 0.05). Eleven children underwent internal sphincter myectomy, and the symptoms of constipation, abdominal distension and enterocolitis were significantly improved after the operation (P < 0.01). Conclusion: Botulinum toxin injection and internal sphincter myectomy based on the principle of "anorectal balance" can effectively reduce the resting pressure of the anus and relieve intestinal dysfunction, and have satisfactory clinical effect.

Gut dysfunction may be the source of pathological aggregation of alpha-synuclein in the central nervous system through Paraquat exposure in mice.

BACKGROUND: One of the most common types of neurodegenerative diseases (NDDs) is Lewy body disease (LBD), which is characterized by excessive accumulation of α-synuclein (α-syn) in the neurons and affects around 6 million individuals globally. In recent years, due to the environmental factors that can affect the development of this condition, such as exposure to herbicides and pesticides, so it has become a younger disease. Currently, the vast majority of studies on the neurotoxic effects of paraquat (PQ) focus on the late mechanisms of neuronal-glial network regulation, and little is known about the early origins of this environmental factor leading to LBD. OBJECTIVE: To observe the effect of PQ exposure on intestinal function and to explore the key components of communicating the gut-brain axis by establishing a mouse model. METHODS AND RESULTS: In this study, C57BL/6J mice were treated by intraperitoneal injection of 15 mg/kg PQ to construct an LBD time-series model, and confirmed by neurobehavioral testing and pathological examination. After PQ exposure, on the one hand, we found that fecal particle counts and moisture content were abnormal. on the other hand, we found that the expression levels of colonic tight junction proteins decreased, the expression levels of inflammatory markers increased, and the diversity and abundance of gut microbiota altered. In addition, pathological aggregation of α-syn was consistent in the colon and midbrain, and the metabolism and utilization of short-chain fatty acids (SCFAs) were also markedly altered. This suggests that pathological α-syn and SCFAs form the gut may be key components of the communicating gut-brain axis. CONCLUSION: In this PQ-induced mouse model, gut microbiota disruption, intestinal epithelial barrier damage, and inflammatory responses may be the main causes of gut dysfunction, and pathological α-syn and SCFAs in the gut may be key components of the communicating gut-brain axis.

Melanin-concentrating hormone promotes anxiety and intestinal dysfunction via basolateral amygdala in mice.

The limbic system plays a pivotal role in stress-induced anxiety and intestinal disorders, but how the functional circuits between nuclei within the limbic system are engaged in the processing is still unclear. In our study, the results of fluorescence gold retrograde tracing and fluorescence immunohistochemistry showed that the melanin-concentrating hormone (MCH) neurons of the lateral hypothalamic area (LHA) projected to the basolateral amygdala (BLA). Both chemogenetic activation of MCH neurons and microinjection of MCH into the BLA induced anxiety disorder in mice, which were reversed by intra-BLA microinjection of MCH receptor 1 (MCHR1) blocker SNAP-94847. In the chronic acute combining stress (CACS) stimulated mice, SNAP94847 administrated in the BLA ameliorated anxiety-like behaviors and improved intestinal dysfunction via reducing intestinal permeability and inflammation. In conclusion, MCHergic circuit from the LHA to the BLA participates in the regulation of anxiety-like behavior in mice, and this neural pathway is related to the intestinal dysfunction in CACS mice by regulating intestinal permeability and inflammation.

The Intestinal Microbiota and Metabolites in the Gut-Kidney-Heart Axis of Chronic Kidney Disease.

Emerging evidences demonstrate the involvement of gut microbiota in the progression of chronic kidney disease (CKD) and CKD-associated complications including cardiovascular disease (CVD) and intestinal dysfunction. In this review, we discuss the interactions between the gut, kidney and heart in CKD state, and elucidate the significant role of intestinal microbiota in the gut-kidney-heart axis hypothesis for the pathophysiological mechanisms of these diseases, during which process mitochondria may serve as a potential therapeutic target. Dysregulation of this axis will lead to a vicious circle, contributing to CKD progression. Recent studies suggest novel therapies targeting gut microbiota in the gut-kidney-heart axis, including dietary intervention, probiotics, prebiotics, genetically engineered bacteria, fecal microbiota transplantation, bacterial metabolites modulation, antibiotics, conventional drugs and traditional Chinese medicine. Further, the identification of specific microbial communities and their corresponding pathophysiological metabolites and the illumination of the gut-kidney-heart axis may contribute to innovative basic research, clinical trials and therapeutic strategies against CKD progression and uremic complications in CKD patients.

Factores que afectan la meta calórica en pacientes de cuidados intensivos con insuficiencia o falla intestinal. Revisión sistemática / Factors affecting caloric goal in intensive care patients with intestinalinsufficiency or failure. Systematic review

Introducción: La insuficiencia y falla intestinal hacenparte de la disfunción gastrointestinal y ocurren en cerca del60% de los pacientes hospitalizados en cuidado intensivo, locual afecta el cumplimiento de las metas nutricionales. Objetivo: Establecer los factores que afectan el cumpli-miento de la meta calórica del soporte nutricional en pa-cientes de cuidado intensivo con insuficiencia o falla intes-tinal. Métodos: Se consultó en las bases de datos de MEDLINE,SCOPUS y COCHRANE, desde enero del 2015 hasta septiem-bre del 2020, sobre meta calórica e insuficiencia y falla intes-tinal en pacientes críticos. Dos investigadores realizaron labúsqueda, aplicaron los criterios de selección, extrajeron losdatos, y evaluaron la calidad metodológica de los estudios. Sehizo una matriz de comparación para los artículos encontra-dos y se evaluó su validez. Resultados: Los artículos evaluados fueron heterogeneose incluyeron pacientes críticos con diferentes trastornos gas-trointestinales. Los determinantes identificados como factoresque afectan la meta calórica fueron: intolerancia gástrica, nutrición postpilórica, uso de opioides, uso de proquinéticos,diarrea y equipo multidisciplinario. Conclusiones: Esta revisión, resalta la ausencia de pará-metros validados para calificar la insuficiencia o falla intesti-nal en pacientes con enfermedades críticas. Los seis aspectosidentificados que afectan el cumplimiento de la meta calóricase deben evaluar prospectivamente en esta población.(AU)

Introduction: Insufficiency and intestinal failure are partof gastrointestinal dysfunction and the occurrence of some ofthese situations is frequent in about 60% of patients hospi-talized in intensive care, which affects the fulfillment of nutri-tional goals. Objective: To establish the factors that affect the fulfill-ment of the caloric goal of nutritional support in intensive carepatients with intestinal insufficiency or failure. Methods: The MEDLINE, SCOPUS and COCHRANE data-bases were consulted, from January 2015 to September2020, on caloric goal and intestinal insufficiency and failure incritically ill patients. Two investigators conducted the search,applied the selection criteria, extracted the data, and as-sessed the methodological quality of the studies. A comparison matrix was made for the articles found and its validity wasevaluated. Results: The articles evaluated included critical patients,but with different gastrointestinal disorders according to thecut-off points used in each one. The determinants identifiedas factors that affect caloric goal were: gastric intolerance,post-pyloric nutrition, use of opioids, use of prokinetics, diar-rhea, and multidisciplinary team. No unified parameters werefound to measure caloric goal and intestinal insufficiency orfailure in most of the studies. Discussion: The articles evaluated were heterogeneousand included critical patients with different gastrointestinaldisorders. The determinants identified as factors that affectcaloric goal were: gastric intolerance, post-pyloric nutrition,use of opioids, use of prokinetics, diarrhea, and multidiscipli-nary team. Conclusions: This review highlights the absence of vali-dated parameters to qualify intestinal insufficiency or failurein critically ill patients. The six identified aspects that affectthe fulfillment of the caloric goal should be evaluatedprospectively in this population.