Gut Immune System Research Articles

Non-Coding RNAs and Gut Microbiota in the Pathogenesis of Cardiac Arrhythmias: The Latest Update.

Non-coding RNAs (ncRNAs) are indispensable for adjusting gene expression and genetic programming throughout development and for health as well as cardiovascular diseases. Cardiac arrhythmia is a frequent cardiovascular disease that has a complex pathology. Recent studies have shown that ncRNAs are also associated with cardiac arrhythmias. Many non-coding RNAs and/or genomes have been reported as genetic background for cardiac arrhythmias. In general, arrhythmias may be affected by several functional and structural changes in the myocardium of the heart. Therefore, ncRNAs might be indispensable regulators of gene expression in cardiomyocytes, which could play a dynamic role in regulating the stability of cardiac conduction and/or in the remodeling process. Although it remains almost unclear how ncRNAs regulate the expression of molecules for controlling cardiac conduction and/or the remodeling process, the gut microbiota and immune system within the intricate networks might be involved in the regulatory mechanisms. This study would discuss them and provide a research basis for ncRNA modulation, which might support the development of emerging innovative therapies against cardiac arrhythmias.

Development of Gut Microbiota in the First 1000 Days after Birth and Potential Interventions.

The first 1000 days after birth represent a critical window for gut microbiome development, which is essential for immune system maturation and overall health. The gut microbiome undergoes major changes during this period due to shifts in diet and environment. Disruptions to the microbiota early in life can have lasting health effects, including increased risks of inflammatory disorders, autoimmune diseases, neurological disorders, and obesity. Maternal and environmental factors during pregnancy and infancy shape the infant gut microbiota. In this article, we will review how maintaining a healthy gut microbiome in pregnancy and infancy is important for long-term infant health. Furthermore, we briefly include fungal colonization and its effects on the host immune function, which are discussed as part of gut microbiome ecosystem. Additionally, we will describe how potential approaches such as hydrogels enriched with prebiotics and probiotics, gut microbiota transplantation (GMT) during pregnancy, age-specific microbial ecosystem therapeutics, and CRISPR therapies targeting the gut microbiota hold potential for advancing research and development. Nevertheless, thorough evaluation of their safety, effectiveness, and lasting impacts is crucial prior to their application in clinical approach. The article emphasizes the need for continued research to optimize gut microbiota and immune system development through targeted early-life interventions.

Polystyrene may alter the cooperation mechanism of gut microbiota and immune system through co-exposure with DCBQ

The toxicity of Polystyrene (PS) may be higher through co-exposure with other pollutants. Human can simultaneously face the challenges from the various pollutants. Nevertheless, little research has been done on the combined effects of PS and 2,6-dichloro-p-benzoquinone (DCBQ) disinfection byproduct. Considering the potential risk of PS and DCBQ, we aimed to illustrate the effects of PS in combination with DCBQ on the immune responses of mice. We found that cotreatment of DCBQ and PS may inhibit the activity of spleen CD4+ T cells and interfere with the normal function of the immune system. Further research found that DCBQ + PS resulted in increasing amount of the inflammatory cells in intestine via histopathological evaluation. The reason might be that DCBQ + PS has changed the composition of intestinal flora, abnormally activated intestinal macrophage, and inhibited the expression of immune-related genes, thus leading to intestinal immune disorders and triggering intestinal inflammation. In summary, PS may alter the cooperation mechanism of gut microbiota and immune system through co-exposure with DCBQ. Current results suggested that more attention should be paid to the combined toxic effects of environmental contaminants.

Use of Spirulina platensis and Curcuma longa as Nutraceuticals in Poultry

Since the banning of antibiotics in animal feeds (2006), there has been an increase in the number of studies looking for alternatives to stimulate the gut immune system. The main objective of our review article is to underline the nutraceutical properties of Curcuma longa and Spirulina platensis in the broiler chicken industry, and the experimental data were obtained by analyzing literature sources. Spirulina platensis is widely recognized as a valuable protein source, containing approximately 55–70% protein, 25% carbohydrates, essential amino acids, and 18% fatty acids. It is also rich in various vitamins like thiamin, riboflavin, pyridoxine, vitamin B12, vitamin C, gamma-linolenic acid, phycocyanins, tocopherols, chlorophyll, beta-carotenes, carotenoids, exhibiting positive effects on growth performance, gut integrity, and immunity. The anti-inflammatory effect of spirulina supplementation at different levels showed a decrease in caspase-3 and the TNF-α immunolabeling index; a reduction in IL-1β, IL-2 and IFN-γ; and an increase in the expression of the anti-inflammatory cytokine IL-4. Spirulina inhibits the synthesis of cytokines IL-1, IL-6, and TNF-gamma in addition to the activities of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) enzymes. Turmeric also positively influences the growth, egg production, and overall health of chickens. Curcumin, the most potent component of turmeric, possesses additional pharmacological activities, including hepatoprotective, immunostimulant, and anticancer effects. Its immunomodulatory properties greatly enhance the immune system response, acting as a natural antibiotic against pathogens and decreasing levels of proinflammatory interleukins IL-1β, IL-6, IL-2, IL-18, and TNF-α.

What's gut got to do with it? The role of the microbiota and inflammation in the development of adiposity and obesity.

Obesity is a complex and heterogeneous disease characterized by increased adiposity, ie, the accumulation of lipids and the growth of adipose tissue. In this mini-review, we explore the important role of the gut microbiota and immune system in the development of adiposity. Dysbiosis of the microbiota leads to increased permeability of the gut barrier and bacterial products in the bloodstream, which triggers metabolic inflammation of adipose tissue, muscle, and liver. Inflammation in these highly metabolic organs exacerbates adiposity and contributes to the development of comorbidities associated with obesity. Studies in animal models that manipulate the microbiota and/or inflammation have shown promise in the treatment of obesity.

Intestinal Colonization of Campylobacter jejuni and Its Hepatic Dissemination Are Associated with Local and Systemic Immune Responses in Broiler Chickens.

Campylobacter jejuni is an important foodborne pathogen. Despite the lack of clinical signs associated with its colonization in poultry, it has been reported to interact with the intestinal immune system. However, little is known about the interaction between C. jejuni and the chicken immune system, especially in the context of hepatic dissemination. Therefore, to follow up on our previous study showing intestinal colonization and hepatic spread of C. jejuni, cecal tonsils and liver samples were collected from these birds to determine the mRNA levels of chemokines and cytokines. Serum samples were also collected to determine serum amyloid A (SAA) concentrations and specific IgY titers. Lack of Th17 induction was observed in the cecal tonsils of only the liver-contaminated groups. This hepatic dissemination was accompanied by innate, Th1 and Th2 immune responses in livers, as well as an increase in SAA concentrations and specific IgY levels in sera. Campylobacter appears to be able to restrain the induction of the chicken gut immunity in particular conditions, possibly enhancing its hepatic dissemination and thus eliciting systemic immune responses. Although Campylobacter is often recognized as a commensal-like bacterium in chickens, it seems to modulate the gut immune system and induce systemic immunity.

Polysaccharides from Paecilomyces hepiali Prevent Acute Colitis in Association with Modulating Gut Microbiota and Treg/Th17 Immune Balance in Mice

Cordyceps exopolysaccharide (CEP) has shown emerging potential in adjustment of gut microbiota and immune cell function. In this study, a water-soluble CEP with a molecular weight of 58.14 kDa was extracted from the fermentation broth of Paecilomyces hepiali, an endophytic fungus of Cordyceps sinensis. Our results indicated that Paecilomyces hepiali polysaccharide (PHP) showed significantly preventive potential on dextran sulfate sodium (DSS)-induced colitis in mice, which can prevent colon shortening, reduce intestinal epithelial cell (IEC) destruction, suppress inflammatory cell infiltration, and regulate the balance between regulatory T (Treg) cells and T helper type 17 (Th17) cells. Meanwhile, the disturbed gut microbiota was partially restored after PHP treatment. Further Pearson correlation coefficient analyses exhibited that the alteration of the gut microbiota was significantly related to adjustment of the IEC barrier and Treg/Th17 balance. In conclusion, all findings proposed that purified PHP has the potential to develop into a promising agent for colitis prevention and adjuvant therapy via maintaining intestinal homeostasis of gut microbiota and immune system.

Gut microbiome-mediated mechanisms in aging-related diseases: are probiotics ready for prime time?

Chronic low-grade inflammation affects health and is associated with aging and age-related diseases. Dysregulation of the gut flora is an important trigger for chronic low-grade inflammation. Changes in the composition of the gut flora and exposure to related metabolites have an effect on the inflammatory system of the host. This results in the development of crosstalk between the gut barrier and immune system, contributing to chronic low-grade inflammation and impairment of health. Probiotics can increase the diversity of gut microbiota, protect the gut barrier, and regulate gut immunity, thereby reducing inflammation. Therefore, the use of probiotics is a promising strategy for the beneficial immunomodulation and protection of the gut barrier through gut microbiota. These processes might positively influence inflammatory diseases, which are common in the elderly.

The Effects of a High-Fat Diet on Inflammatory Bowel Disease

The interactions among diet, intestinal immunity, and microbiota are complex and play contradictory roles in inflammatory bowel disease (IBD). An increasing number of studies has shed light on this field. The intestinal immune balance is disrupted by a high-fat diet (HFD) in several ways, such as impairing the intestinal barrier, influencing immune cells, and altering the gut microbiota. In contrast, a rational diet is thought to maintain intestinal immunity by regulating gut microbiota. In this review, we emphasize the crucial contributions made by an HFD to the gut immune system and microbiota.

Dysfunction of the Gut Microbiome and its Onset Progression of Chronic and Mental Health Disorders

The gut microbiome is a complex community of microbes that inhabits the gastrointestinal tract and plays a crucial role in maintaining human health. Recent research has demonstrated that gut dysbiosis, or an imbalance in the microbiome, is associated with the development of various chronic and psychiatric diseases, such as obesity, cardiovascular disease, and depression. The mechanisms by which gut dysbiosis contributes to disease development involve alterations in the gut-brain axis, gut-liver axis, and gut-immune system interactions. Studies have shown that gut microbiome dysbiosis can cause up-regulation of certain pathways involved in disease development, including systemic inflammation, oxidative stress, and intestinal permeability. Additionally, gut dysbiosis has been linked to alterations in neurotransmitter synthesis and gut hormone secretion, which can influence the brain and contribute to mood and cognitive disorders. Further research is necessary to fully comprehend the mechanisms underlying this relationship and to develop effective strategies for the prevention and treatment of chronic and psychiatric diseases. In conclusion, gut microbiome dysbiosis plays a critical role in the up-regulation and development of chronic and psychiatric diseases and is an area of growing interest in the scientific community. Further investigation is needed to fully understand the mechanisms underlying this relationship and to develop effective treatments and interventions. Keywords: Gut microbiome , chronic, mental health, dysfunction

The Dietary Sugars Intake: The Role In Alzheimer’s Disease Pathomechanism

Alzheimer’s disease is a common neurodegenerative disease that affect elderly and it became a serious global burden for years. Despite many studies have been performed, an effective cure for Alzheimer’s was still not be found. Therefore, it is necessary to not only focus on curative methods but also preventive methods with modifiable risk factors and underlying disease, for example lifestyle and metabolic disease, as potential approach in Alzheimer’s disease prevention in the future. The excessive dietary sugar intake has been suggested as a risk factor of many diseases such as metabolic disease and cognitive impairment disease. It may promote cognitive declines through some pathways such as induce alteration of gut microbiomes, metabolism and immune system. These abnormal processes may evoke amyloid β plaque formation and neurofibrillary tangles in brain cells as the effect of chronic inflammation. Chronic inflammation has been widely studied as the hallmark of Alzheimer’s disease pathology. Therefore, the correlation between dietary sugar and impairment cognitive, specifically Alzheimer’s disease will be summarized.

E. coli Nissle 1917 ameliorates mitochondrial injury of granulosa cells in polycystic ovary syndrome through promoting gut immune factor IL-22 via gut microbiota and microbial metabolism.

Gut microbiota and its metabolites have regulatory effects on PCOS related ovarian dysfunction and insulin resistance. Escherichia coli Nissle 1917 (EcN) is a genetically controlled probiotic with an excellent human safety record for improving gut microbiome metabolic disorders and immune system disorders. Here we focused to explore the application and effect of probiotic EcN on the gut microbiota-metabolism-IL-22-mitochondrial damage axis in PCOS. PCOS mice were constructed with dehydroepiandrosterone (DHEA) and treated with EcN, FMT or IL-22 inhibitors. Clinically control and PCOS subjects were included for further analysis. Serum and follicular fluid supernatant levels of sex hormones, insulin, glucose, cholesterol, and inflammatory factors were detected by ELISA and biochemical reagents. The pathological changes of ovarian tissues were observed by HE staining. The JC-1 level and COX4 gene expression in granulosa cells was detected by ELISA and RT-qPCR. The expressions of progesterone receptor A (PR-A), LC3II/I, Beclin1, p62 and CytC were detected by western blot. The number of autophagosomes in granulosa cells was observed by electron microscopy. 16S rRNA and LC-MS/MS were used to analyze the changes of gut microbiota and metabolism. EcN promoted the recovery of sex hormone levels and ovarian tissue morphology, promoted the expression of IL-22, COX4 and PR-A in granulosa cells, and inhibited mitophagy in PCOS mice. EcN decreased the number of gut microbiota, and significantly increased the abundance of Adlercreutzia, Allobaculum, Escherichia-Shigella and Ileibacterium in PCOS mice. EcN improved metabolic disorders in PCOS mice by improving Amino sugar and nucleotide sugar metabolism pathways. IL-22 was positively associated with Ileibacterium, Adlercreutzia and Progesterone, negatively associated with RF39, Luteinizing hormone, Testosterone, N-Acetylglucosamin, L-Fucose and N-Acetylmannosamin. FMT reconfirmed that EcN ameliorated mitochondrial damage in granulosa cells of PCOS mice by gut microbiota, but this process was blocked by IL-22 inhibitor. Clinical trials have further demonstrated reduced IL-22 levels and mitochondrial damage in granulosa cells in PCOS patients. EcN improved IL-22 level and mitochondrial damage of granulosa cells in PCOS mice by promoting the recovery of sex hormone levels and ovarian tissue morphology, inhibiting the amount of gut microbiota, and promoting amino sugar and nucleotide sugar metabolism.

Altered endocannabinoidome bioactive lipid levels accompany reduced DNBS-induced colonic inflammation in germ-free mice

BackgroundGut microbiota are involved in the onset and development of chronic intestinal inflammation. The recently described endocannabinoidome (eCBome), a diverse and complex system of bioactive lipid mediators, has been reported to play a role in various physio-pathological processes such as inflammation, immune responses and energy metabolism. The eCBome and the gut microbiome (miBIome) are closely linked and form the eCBome - miBIome axis, which may be of special relevance to colitis.MethodsColitis was induced in conventionally raised (CR), antibiotic-treated (ABX) and germ-free (GF) mice with dinitrobenzene sulfonic acid (DNBS). Inflammation was assessed by Disease Activity Index (DAI) score, body weight change, colon weight-length ratio, myeloperoxidase (MPO) activity and cytokine gene expression. Colonic eCBome lipid mediator concentrations were measured by HPLC-MS /MS.ResultsGF mice showed increased levels of anti-inflammatory eCBome lipids (LEA, OEA, DHEA and 13- HODE-EA) in the healthy state and higher MPO activity. DNBS elicited reduced inflammation in GF mice, having lower colon weight/length ratios and lower expression levels of Il1b, Il6, Tnfa and neutrophil markers compared to one or both of the other DNBS-treated groups. Il10 expression was also lower and the levels of several N-acyl ethanolamines and 13-HODE-EA levels were higher in DNBS-treated GF mice than in CR and ABX mice. The levels of these eCBome lipids negatively correlated with measures of colitis and inflammation.ConclusionsThese results suggest that the depletion of the gut microbiota and subsequent differential development of the gut immune system in GF mice is followed by a compensatory effect on eCBome lipid mediators, which may explain, in part, the observed lower susceptibility of GF mice to develop DNBS-induced colitis.

Oral exposure to Escherichia colitoxin protects against lung allergen-induced inflammation

Abstract Recent studies suggest that the intestinal microenvironment regulate lung immune cells. Conversely, changes in the lung can modulate the gut immune system. Yet, mucosal-associated immune responses have been studied in a compartmentalized manner, as if there is no communication between different organs. Thus, the role of the gut-lung axis in mucosal immune responses is poorly understood. Using enterotoxigenic Escherichia coli (ETEC), we established a model of intestine-localized infection without translocation to any other tissue. In response to ETEC, type 2 innate lymphoid cells (ILC2s) and eosinophils accumulated in the intestinal lamina propria, even after bacterial clearance. In addition, oral ETEC transiently increased the numbers of ILC2 and eosinophils in the lung parenchyma. To test if oral ETEC promote lung immune responses to allergen, we exposed mice that recently cleared ETEC to intranasal papain/ovalbumin allergy induction model. Unexpectedly, ETEC-exposed mice were significantly resistant to allergen-induced lung inflammation, with reduced number of ILC2, Type 2 effector CD4 +T cells (Th2) and eosinophils. Paradoxically, oral ETEC-induced protection against lung allergen exposure was dependent on IL-33: IL-33KO mice developed partial lung inflammation in this model, and no protection induced by ETEC exposure was observed. Importantly, protection from allergy was achieved with ETEC heat-labile toxin (LT) oral exposure; we also found that the toxicity domain of LT is needed for this protection. Our results indicate that gastrointestinal bacterial infection mediators (toxins) negatively regulate the onset of allergic inflammation and may provide a novel immunological basis for the “hygiene hypothesis”. R01AI170649 FAPESP 2021/15185-2

Effect of Nanomaterials on Gut Microbiota.

Nanomaterials are widely employed in everyday life, including food and engineering. Food additives on a nanoscale can enter the body via the digestive tract. The human gut microbiota is a dynamically balanced ecosystem composed of a multitude of microorganisms that play a crucial role in maintaining the proper physiological function of the digestive tract and the body's endocrine coordination. While the antibacterial capabilities of nanomaterials have received much interest in recent years, their impacts on gut microbiota ought to be cautioned about and explored. Nanomaterials exhibit good antibacterial capabilities in vitro. Animal studies have revealed that oral exposure to nanomaterials inhibits probiotic reproduction, stimulates the inflammatory response of the gut immune system, increases opportunistic infections, and changes the composition and structure of the gut microbiota. This article provides an overview of the impacts of nanomaterials, particularly titanium dioxide nanoparticles (TiO2 NPs), on the gut microbiota. It advances nanomaterial safety research and offers a scientific foundation for the prevention, control, and treatment of illnesses associated with gut microbiota abnormalities.

Probiotics Influence Gut Microbiota and Tumor Immune Microenvironment to Enhance Anti-Tumor Efficacy of Doxorubicin.

Probiotics have been reported to influence the gut microbiota and immune system in various diseases. Now, the potential impacts of probiotics on tumor treatment still need to be investigated. In this study, three strains of probiotics, Bifidobacterium breve BBr60 (BBr60), Pediococcus pentosaceus PP06 (PP06), and Bifidobacterium longum subsp. longum BL21 (BL21) were investigated for their combination with chemotherapeutic drugs doxorubicin (DOX). Our study showed that PP06 and BL21 have good performance in gastric acid, bile salt, and intestinal fluid tolerance, antimicrobial activity to pathogenic Staphylococcus aureus, and adhesion to Caco-2 cells. Besides, the probiotics all exhibited antioxidant effect, especially BL21. In vitro cytotoxicity and in vivo animal studies revealed that probiotics used alone could not directly induce anti-tumor effects, but the combination of PP06/BL21 and DOX exhibits a higher inhibition rate than DOX alone, via recruitment and infiltration of immune cells in the tumor region. After 16S rRNA analysis of fecal samples from animal models, it was found that BL21 could increase the abundance of Akkermansia, which may also play a role in regulating the tumor microenvironment to improve immune response. In conclusion, BL21 and PP06 in this study could enhance the anti-tumor efficacy by influencing the gut microbiota and tumor immune microenvironment.

Agaricus subrufescens fermented rye affects the development of intestinal microbiota, local intestinal and innate immunity in suckling-to-nursery pigs

BackgroundAgaricus subrufescens is considered as one of the most important culinary-medicinal mushrooms around the world. It has been widely suggested to be used for the development of functional food ingredients to promote human health ascribed to the various properties (e.g., anti-inflammatory, antioxidant, and immunomodulatory activities). In this context, the interest in A. subrufescens based feed ingredients as alternatives for antibiotics has also been fuelled during an era of reduced/banned antibiotics use. This study aimed to investigate the effects of a fermented feed additive -rye overgrown with mycelium (ROM) of A. subrufescens—on pig intestinal microbiota, mucosal gene expression and local and systemic immunity during early life. Piglets received ROM or a tap water placebo (Ctrl) perorally every other day from day 2 after birth until 2 weeks post-weaning. Eight animals per treatment were euthanized and dissected on days 27, 44 and 70.ResultsThe results showed ROM piglets had a lower inter-individual variation of faecal microbiota composition before weaning and a lower relative abundance of proteobacterial genera in jejunum (Undibacterium and Solobacterium) and caecum (Intestinibacter and Succinivibrionaceae_UCG_001) on day 70, as compared to Ctrl piglets. ROM supplementation also influenced gut mucosal gene expression in both ileum and caecum on day 44. In ileum, ROM pigs showed increased expression of TJP1/ZO1 but decreased expression of CLDN3, CLDN5 and MUC2 than Ctrl pigs. Genes involved in TLR signalling (e.g., TICAM2, IRAK4 and LY96) were more expressed but MYD88 and TOLLIP were less expressed in ROM pigs than Ctrl animals. NOS2 and HIF1A involved in redox signalling were either decreased or increased in ROM pigs, respectively. In caecum, differentially expressed genes between two groups were mainly shown as increased expression (e.g., MUC2, PDGFRB, TOLLIP, TNFAIP3 and MYD88) in ROM pigs. Moreover, ROM animals showed higher NK cell activation in blood and enhanced IL-10 production in ex vivo stimulated MLN cells before weaning.ConclusionsCollectively, these results suggest that ROM supplementation in early life modulates gut microbiota and (local) immune system development. Consequently, ROM supplementation may contribute to improving health of pigs during the weaning transition period and reducing antibiotics use.

Gut dysbiosis in autoimmune diseases: Association with mortality.

To better understand the impact of gut dysbiosis on four autoimmune diseases [Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS)], this review investigated the altered gut bacteria in each disease and the shared ones among the four diseases. The enriched gut bacteria shared by three of the four autoimmune diseases were Streptococcus, Prevotella, and Eggerthella, which are associated with autoantibody production or activation of Th17 cells in immune-related diseases. On the other hand, Faecalibacterium comprises depleted gut bacteria shared by patients with SLE, MS, and SS, which is associated with various anti-inflammatory activities. The indexes of gut dysbiosis, defined as the number of altered gut bacterial taxa divided by the number of studies in SLE, MS, RA, and SS, were 1.7, 1.8, 0.7, and 1.3, respectively. Interestingly, these values presented a positive correlation trend with the standardized mortality rates -2.66, 2.89, 1.54, and 1.41, respectively. In addition, shared altered gut bacteria among the autoimmune diseases may correlate with the prevalence of polyautoimmunity in patients with SLE, SS, RA, and MS, that is, 41 percent, 32.6 percent, 14 percent, and 1-16.6 percent, respectively. Overall, this review suggests that gut dysbiosis in autoimmune diseases may be closely related to the failure of the gut immune system to maintain homeostasis.

Alterations in gut immunological barrier in SARS-CoV-2 infection and their prognostic potential.

Although coronavirus disease 2019 (COVID-19) is primarily associated with mild respiratory symptoms, a subset of patients may develop more complicated disease with systemic complications and multiple organ injury. The gastrointestinal tract may be directly infected by SARS-CoV-2 or secondarily affected by viremia and the release of inflammatory mediators that cause viral entry from the respiratory epithelium. Impaired intestinal barrier function in SARS-CoV-2 infection is a key factor leading to excessive microbial and endotoxin translocation, which triggers a strong systemic immune response and leads to the development of viral sepsis syndrome with severe sequelae. Multiple components of the gut immune system are affected, resulting in a diminished or dysfunctional gut immunological barrier. Antiviral peptides, inflammatory mediators, immune cell chemotaxis, and secretory immunoglobulins are important parameters that are negatively affected in SARS-CoV-2 infection. Mucosal CD4+ and CD8+ T cells, Th17 cells, neutrophils, dendritic cells, and macrophages are activated, and the number of regulatory T cells decreases, promoting an overactivated immune response with increased expression of type I and III interferons and other proinflammatory cytokines. The changes in the immunologic barrier could be promoted in part by a dysbiotic gut microbiota, through commensal-derived signals and metabolites. On the other hand, the proinflammatory intestinal environment could further compromise the integrity of the intestinal epithelium by promoting enterocyte apoptosis and disruption of tight junctions. This review summarizes the changes in the gut immunological barrier during SARS-CoV-2 infection and their prognostic potential.

Effects of pair-housing pubertal and adult male and female mice on LPS-induced age-dependent immune responses: A potential role for the gut microbiota

Puberty is a critical period of development that is marked by the maturation of the stress and immune systems. There are marked age and sex differences in peripheral and central inflammatory responses to an immune challenge between pubertal and adult mice. Given the strong link between the gut microbiome and immune system, it is possible that the age and sex differences in immune responses are mediated by age and sex differences in gut microbial composition. The current study investigated whether cohousing adult and pubertal CD1 mice through three weeks of pair-housing, with the potential for microbiome exchange via coprophagy and other close contact, could mitigate age-dependent immune responses. Cytokine concentrations in the blood and cytokine mRNA expression in the brain were assessed following exposure to the immune challenge lipopolysaccharide (LPS). The results show that all mice displayed increased cytokine concentrations in serum and central cytokine mRNA expression in the hippocampus, hypothalamus and prefrontal cortex (PFC) at eight hours following LPS treatment. Pubertal male and female mice, that were pair-housed with a pubertal counterpart, displayed lower cytokine concentrations in serum and lower cytokine mRNA expression in the brain compared to adult mice that were pair-housed with an adult counterpart. However, when adult and pubertal mice were pair-housed, the age differences in both peripheral cytokine concentrations and central cytokine mRNA expression were mitigated. We also found that pair-housing adult and pubertal mice eliminated the age difference in gut bacterial diversity. These results suggest that microbial composition could be involved in modulating these age-associated immune responses and thus may represent a potential therapeutic target.