Gut Microbial Homeostasis Research Articles

Effects of ex situ conservation on diversity and function of the gut microbiota of the Tibetan wild ass (Equus kiang).

Ex situ conservation is the main method for the protection of endangered wildlife. To explore the effect of ex situ conservation on the gut microbiota of the kiang (Equus kiang), metagenomic sequencing combined with bioinformatics analysis was used to investigate the composition and function of the gut microbiota of the kiang. The results showed that ex situ conservation not only protected wildlife, but also affected the composition and function of gut microbiota, as well as the health of animals. In the zoo, the ratio of the relative abundance of Firmicutes to that of Bacteroidetes (F/B) is higher, clusters of potentially pathogenic bacteria (such as Catonella, Catonella, and Mycoplasma) are more numerous, the abundance of resistance genes is higher, and the abundance of metabolic functions is increased. The dynamic changes of the gut microbiota also played an important role in the nutritional absorption, energy metabolism, and environmental adaptation of the kiang. Improving the rearing environment and increasing food diversity play important roles for increasing the diversity of gut microbiota, reducing the spread of potentially pathogenic bacteria, and reducing diseases. In the wild, especially in winter and in food-deficient areas, food supplementation can enhance the gut microbial homeostasis of wild animals and reduce the impact of crises. In depth studies of the gut microbial function of wildlife have important implications for improving ex situ conservation.

Synergistic Target of Intratumoral Microbiome and Tumor by Metronidazole–Fluorouridine Nanoparticles

Clinical and experimental evidence confirmed bacterial infiltration in a variety of tumors, which is related to the progression and therapeutic effects of the tumors. Although the administration of antibiotics inhibits the growth of bacteria inside the tumor, systemic distribution of antibiotics induces an imbalance of other microbiomes in the body, which in turn leads to the development of new diseases. To address this clinical challenge, we nanonized an antibiotic in this study. Metronidazole, an antibiotic against broad anaerobes, was linked to fluorouridine to form an amphiphilic small molecule, metronidazole-fluorouridine, which further autoassembled as metronidazole-fluorouridine nanoparticles (MTI-FDU) in a hydrophilic solution. The disulfide bond in the linker cleaves in response to high levels of glutathione (GSH) in the tumor microenvironment. The synergistic antitumor effect of MTI-FDU was observed in two animal models of gut cancer with intratumoral bacteria. Analysis revealed that metronidazole delivered by nanoparticles attacked bacteria inside the tumor, while it had minimal effect on gut microbial homeostasis. Further experiments at the cellular and molecular levels disclosed that MTI-FDU shaped the tumor immune microenvironment through clearance of bacteria and bacterial products. In conclusion, we achieved a synergistic antitumor effect by a dual target of both the intratumoral microbiome and tumor cells. Antibiotic-composed nanoparticles have a clinical advantage in the treatment of tumors with bacteria infiltration, which kill pro-tumor bacteria efficiently as well as keep a balanced microbiota of the patient.

Jinhong decoction protects sepsis-associated acute lung injury by reducing intestinal bacterial translocation and improving gut microbial homeostasis.

Background: Currently no specific treatments are available for sepsis and the associated syndromes including acute lung injury (ALI). Jinhong Decoction (JHD) is a traditional Chinese prescription, and it has been applied clinically as an efficient and safe treatment for sepsis, but the underlying mechanism remains unknown. The aim of the study was to explore the potential mechanisms of JHD ameliorating sepsis and concurrent ALI. Methods: The cecum ligation puncture (CLP)- induced murine sepsis model was established for determining the efficacy of JHD protecting CLP and ALI. The role of gut microbiota involved in the efficacy of JHD was evaluated by 16S rRNA sequencing and fecal microbiota transplantation (FMT). Translocation of intestinal Escherichia coli (E. coli) to lungs after CLP was verified by qPCR and in vivo-imaging. Intestinal permeability was analyzed by detecting FITC-dextran leakness. Junction proteins were evaluated by Western blotting and immunofluorescence. Results: JHD treatment remarkably increased survival rate of septic mice and alleviated sepsis-associated lung inflammation and injury. FMT suggested that the protective role for JHD was mediated through the regulation of gut microbiota. We further revealed that JHD administration partially restored the diversity and configuration of microbiome that was distorted by CLP operation. Of interest, the intestinal bacteria, E. coli particularly, was found to translocate into the lungs upon CLP via disrupting the intestinal mucosal barrier, leading to the inflammatory response and tissue damage in lungs. JHD impeded the migration and hence lung accumulation of intestinal E. coli, and thereby prevented severe ALI associated with sepsis. This effect is causatively related with the ability of JHD to restore intestinal barrier by up-regulating tight junctions. Conclusion: Our study unveils a mechanism whereby the migration of gut bacteria leads to sepsis-associated ALI, and we demonstrate the potential of JHD as an effective strategy to block this bacterial migration for treating sepsis and the associated immunopathology in the distal organs.

Microbiome-liver crosstalk: A multihit therapeutic target for liver disease

Liver disease has become a leading cause of death, particularly in the West, where it is attributed to more than two million deaths annually. The correlation between gut microbiota and liver disease is still not fully understood. However, it is well known that gut dysbiosis accompanied by a leaky gut causes an increase in lipopolysaccharides in circulation, which in turn evoke massive hepatic inflammation promoting liver cirrhosis. Microbial dysbiosis also leads to poor bile acid metabolism and low short-chain fatty acids, all of which exacerbate the inflammatory response of liver cells. Gut microbial homeostasis is maintained through intricate processes that ensure that commensal microbes adapt to the low oxygen potential of the gut and that they rapidly occupy all the intestinal niches, thus outcompeting any potential pathogens for available nutrients. The crosstalk between the gut microbiota and its metabolites also guarantee an intact gut barrier. These processes that protect against destabilization of gut microbes by potential entry of pathogenic bacteria are collectively called colonization resistance and are equally essential for liver health. In this review, we shall investigate how the mechanisms of colonization resistance influence the liver in health and disease and the microbial-liver crosstalk potential as therapeutic target areas.

Salt-contaminated water exposure induces gut microbial dysbiosis in chickens

Microbes play a crucial role in maintaining health by aiding in digestion, regulating the immune system, producing essential vitamins, and preventing the colonization of harmful bacteria. The stability of the microbiota is, therefore, necessary for overall well-being. However, several environmental factors can negatively affect the microbiota, including exposure to industrial waste, i.e., chemicals, heavy metals, and other pollutants. Over the past few decades, industries have grown significantly, but the wastewater from those industries has seriously harmed the environment and the health of living beings both locally and globally. The current study investigated the effects of salt-contaminated water exposure on gut microbiota in chickens. According to our findings, amplicon sequencing showed 453 OTUs across control and salt-contaminated water exposure groups. Proteobacteria, Firmicutes, and Actinobacteriota were the most dominant phyla in the chickens regardless of treatment. However, exposure to salt-contaminated water resulted in a remarkable decline in gut microbial diversity. While, the beta diversity revealed substantial differences in major gut microbiota components. Moroever, microbial taxonomic investigation indicated that the proportions of one bacterial phylum and nineteen bacterial genera significantly decreased. Also, the levels of one bacterial phylum and thirty three bacterial genera markedly increased under salt-contaminated water exposure, which indicates a disruption in gut microbial homeostasis. Hence the current study provides a basis to explore the effects of salt-contaminated water exposure on the health of vertebrate species.

DEHP exposure elevated cardiovascular risk in obese mice by disturbing the arachidonic acid metabolism of gut microbiota

Phthalate esters (PAEs) are one of the significant classes of emerging contaminants that are increasingly detected in environmental and human samples. Nevertheless, the current toxicity studies rarely report how PAEs affect the cardiovascular system, especially in obese individuals. In this study, diet-induced obese mice and corresponding normal mice were exposed to di(2-ethylhexyl) phthalate (DEHP) by oral gavage at environmentally relevant concentrations and key characteristics of cardiovascular risk were examined. The 16S rRNA and high-resolution mass spectrometry were used to investigate the alterations in the gut microbial profile and metabolic homeostasis. The results indicated that the cardiovascular system of fat individuals was more susceptible to DEHP exposure than mice in the lean group. 16S rRNA-based profiling and correlation analysis collectively suggested DEHP-induced gut microbial remodeling in fed a high-fat diet mice, represented by the abundance of the genus Faecalibaculum. Using metagenomic approaches, Faecalibaculum rodentium was identified as the top-ranked candidate bacterium. Additionally, metabolomics data revealed that DEHP exposure altered the gut metabolic homeostasis of arachidonic acid (AA), which is associated with adverse cardiovascular events. Finally, cultures of Faecalibaculum rodentium were treated with AA in vitro to verify the role of Faecalibaculum rodentium in altering AA metabolism. Our findings provide novel insights into DEHP exposure induced cardiovascular damage in obese individuals and suggest that AA could be used as a potential modulator of gut microbiota to prevent related diseases.

Associated long-term effects of decabromodiphenyl ethane on the gut microbial profiles and metabolic homeostasis in Sprague-Dawley rat offspring

Decabromodiphenyl ethane (DBDPE) as a widely used brominated flame retardant is harmful to human health due to its toxicity, including cardiovascular toxicity, reproductive toxicity, and hepatotoxicity. However, the knowledge of the long-term effects and structural and metabolic function influence on gut microbiota from DBDPE exposure remains limited. This study was mainly aimed at the gut microbiome and fecal metabolome of female rats and their offspring exposed to DBDPE in early life. 16S rRNA gene sequencing demonstrated that maternal DBDPE exposure could increase the α-diversity of gut microbiota in immature offspring while decreasing the abundance of Bifidobacterium, Clostridium, Muribaculum, Escherichia, and Lactobacillus in adult offspring. The nonmetric multidimensional scaling showed a consistency in the alternation of β-diversity between pregnant rats and their adult offspring. Furthermore, the short-chain fatty acids produced by gut microbiota dramatically increased in adult offspring after maternal DBDPE exposure, revealing that DBDPE treatment disrupted the gut microbial compositions and altered the gut community's metabolic functions. Untargeted metabolomics identified 41 differential metabolites and seven metabolic pathways between adult offspring from various groups. Targeted metabolomic showed that maternal high dose DBDPE exposure obviously decreased the level of glutathione, taurine, and l-carnitine in their adult offspring, which verified the correlation between weight loss and amino acid metabolites. An interesting link between some gut bacteria (especially the Firmicutes) and fecal metabolites demonstrated the shifts in gut microbiota may drive the metabolic process of fecal metabolites. The current findings provide new insight into long-term effects on human health.

Seaweed polysaccharide relieves hexavalent chromium-induced gut microbial homeostasis.

Heavy metals released in the environment pose a huge threat to soil and water quality, food safety and public health. Additionally, humans and other mammals may also be directly exposed to heavy metals or exposed to heavy metals through the food chain, which seriously threatens the health of animals and humans. Chromium, especially hexavalent chromium [Cr (VI)], as a common heavy metal, has been shown to cause serious environmental pollution as well as intestinal damage. Thus, increasing research is devoted to finding drugs to mitigate the negative health effects of hexavalent chromium exposure. Seaweed polysaccharides have been demonstrated to have many pharmacological effects, but whether it can alleviate gut microbial dysbiosis caused by hexavalent chromium exposure has not been well characterized. Here, we hypothesized that seaweed polysaccharides could alleviate hexavalent chromium exposure-induced poor health in mice. Mice in Cr and seaweed polysaccharide treatment group was compulsively receive K2Cr2O7. At the end of the experiment, all mice were euthanized, and colon contents were collected for DNA sequencing analysis. Results showed that seaweed polysaccharide administration can restore the gut microbial dysbiosis and the reduction of gut microbial diversity caused by hexavalent chromium exposure in mice. Hexavalent chromium exposure also caused significant changes in the gut microbial composition of mice, including an increase in some pathogenic bacteria and a decrease in beneficial bacteria. However, seaweed polysaccharides administration could ameliorate the composition of gut microbiota. In conclusion, this study showed that seaweed polysaccharides can restore the negative effects of hexavalent chromium exposure in mice, including gut microbial dysbiosis. Meanwhile, this research also lays the foundation for the application of seaweed polysaccharides.

Leonurine Regulates Hippocampal Nerve Regeneration in Rats with Chronic and Unpredictable Mild Stress by Activating SHH/GLI Signaling Pathway and Restoring Gut Microbiota and Microbial Metabolic Homeostasis.

Depression is a highly prevalent and heterogeneous disorder that requires new strategies to overcome depression. In this study, we aimed to investigate whether leonurine modulated hippocampal nerve regeneration in chronic and unpredictable mild stress (CUMS) rats through the SHH/GLI signaling pathway and restoring gut microbiota and microbial metabolic homeostasis. The CUMS rat model was constructed and treated with leonurine. The body weight of rats was recorded, and a series of tests were performed. Western blot was utilized to measure the expression of BDNF and 5-HT in the hippocampus. Then the expression of SHH, GLI, PTCH, and SMO were measured by qRT-PCR and western blot. The colocalization of BrdU+DCX and BrdU+NeuN was evaluated by IF. 16S rDNA high-throughput sequencing was applied to detect the composition and distribution of gut microbiota. The differential metabolites were analyzed by untargeted metabolomics. The correlation between gut microbiota and microbial metabolites was analyzed by Pearson correlation coefficient. After CUMS modeling, the body weight of rats was decreased, and the expression of BDNF and 5-HT were decreased, while the body weight was recovered, and the expression of BDNF and 5-HT were increased after leonurine treatment. Leonurine reversed the reduction in the colocalization of BrdU+DCX and BrdU+NeuN and the reduction in the levels of SHH, GLI, PTCH, and SMO induced by CUMS modeling. Leonurine also restored gut microbiota and microbial metabolites homeostasis in CUMS rats. Furthermore, Prevotellaceae_Ga6A1_group was negatively correlated with 3-Oxocholic acid, nutriacholic acid, and cholic acid. Collectively, leonurine regulated hippocampal nerve regeneration in CUMS rats by activating the SHH/GLI signaling pathway and restoring gut microbiota and microbial metabolic homeostasis.

Acid-tolerant Lactiplantibacillus plantarum ZDY2013 shows a colonization niche preference and interacts with enterotoxigenic Bacillus cereus in specific-pathogen-free mice.

Probiotics have long been utilized as functional food and modulate gut microbial homeostasis, but their colonization niche is mostly unclear and transient, which restrains the development of microbiome-targeted strategies. Lactiplantibacillus (L.) plantarum ZDY2013 is an allochthonous species of the human gastrointestinal tract with acid-tolerant properties. It serves as an antagonistic agent against the food-borne pathogen Bacillus (B.) cereus and a potent regulator of the gut microbiota. However, there is a knowledge gap regarding the colonization dynamics of L. plantarum ZDY2013 in the host intestine and the colonization niche of its interaction with pathogens. Here, we designed a pair of specific primers targeting L. plantarum ZDY2013 based on its whole genome sequence. We evaluated their accuracy and sensitivity with other host-derived strains and confirmed their availability with artificially spiked fecal samples from different mouse models. Additionally, the content of L. plantarum ZDY2013 was quantified by qPCR in fecal samples from BALB/c mice, followed by the analysis of its colonization niche preference. Moreover, the interactions between L. plantarum ZDY2013 and enterotoxigenic B. cereus HN001 were also elucidated. The results revealed that the newly designed primers could identify L. plantarum ZDY2013 with high specificity and were resistant to the influence of the complex fecal matrix and gut microbes from different hosts. Interestingly, the content of mixed L. plantarum ZDY2013 and B. cereus HN001 when orally administered remained higher when compared with the single strain group in BALB/c mice upon discontinuation of intragastric administration. In addition, L. plantarum ZDY2013 was mainly enriched in the large intestine during the ingestion period and maintained the highest content in the stomach after discontinuing supplementation on day 7. Moreover, L. plantarum ZDY2013 colonization neither damaged the intestine nor ameliorated the damage triggered by B. cereus in BALB/c mice. Overall, our study constructed two efficient specific primers targeting L. plantarum ZDY2013 and provided the potential to explore the underlying mechanism of competition between L. plantarum ZDY2013 and pathogens in host species.

Potential Ability of Probiotics in the Prevention and Treatment of Colorectal Cancer.

Colorectal cancer (CRC) is the third most common cancer in the world, and its incidence rate and mortality are on the rise in many countries. In recent years, with the improvement of economic conditions, people's living habits have changed, including lack of physical activity, poor diet patterns and circadian rhythm disorder. These risk factors can change the colon environment and the composition of intestinal microbiota. This state is called intestinal imbalance, which increases the risk of cancer. Probiotics, a class of microorganisms that help maintain gut microbial homeostasis and alleviate dysbiosis, may help prevent inflammation and colorectal cancer. These probiotics inhibit or ameliorate the effects of dysbiosis through the production of short-chain fatty acids (SCFAs), modulation of immunity, maintenance of the intestinal epithelial barrier, pro-apoptotic mechanisms, and other mechanisms. This review aims to explain the interaction between probiotics, the gut microenvironment and the gut microbiota, and summarize reports on the possibility of probiotics in the prevention and treatment of colorectal cancer.

A Comprehensive Review of Thyroid Hormone Metabolism in the Gut and Its Clinical Implications.

Background: The gut is a target organ of thyroid hormone (TH) that exerts its action via the nuclear thyroid hormone receptor α1 (TRα1) expressed in intestinal epithelial cells. THs are partially metabolized via hepatic sulfation and glucuronidation, resulting in the production of conjugated iodothyronines. Gut microbiota play an important role in peripheral TH metabolism as they produce and secrete enzymes with deconjugation activity (β-glucuronidase and sulfatase), via which TH can re-enter the enterohepatic circulation. Summary: Intestinal epithelium homeostasis (the finely tuned balance between cell proliferation and differentiation) is controlled by the crosstalk between triiodothyronine and TRα1 and the presence of specific TH transporters and TH-activating and -inactivating enzymes. Patients and experimental murine models with a dominant-negative mutation in the TRα exhibit gross abnormalities in the morphology of the intestinal epithelium and suffer from severe symptoms of a dysfunctional gastrointestinal tract. Over the past decade, gut microbiota has been identified as an essential factor in health and disease, depending on its compositional and functional profile. This has led to a renewed interest in the so-called gut-thyroid axis. Disruption of gut microbial homeostasis (dysbiosis) is associated with autoimmune thyroid disease (AITD), including Hashimoto's thyroiditis, Graves' disease, and Graves' orbitopathy. These studies reviewed here provide new insights into the gut microbiota roles in thyroid disease pathogenesis and may be an initial step toward microbiota-based therapies in AITD. However, it should be noted that cause-effect mechanisms remain to be proven, for which prospective cohort studies, randomized clinical trials, and experimental studies are needed. Conclusion: This review aims at providing a comprehensive insight into the interplay between TH metabolism and gut homeostasis.

Pasture intake protects against commercial diet-induced lipopolysaccharide production facilitated by gut microbiota through activating intestinal alkaline phosphatase enzyme in meat geese.

Diet strongly affects gut microbiota composition, and gut bacteria can influence the intestinal barrier functions and systemic inflammation through metabolic endotoxemia. In-house feeding system (IHF, a low dietary fiber source) may cause altered cecal microbiota composition and inflammatory responses in meat geese via increased endotoxemia (lipopolysaccharides) with reduced intestinal alkaline phosphatase (ALP) production. The effects of artificial pasture grazing system (AGF, a high dietary fiber source) on modulating gut microbiota architecture and gut barrier functions have not been investigated in meat geese. Therefore, this study aimed to investigate whether intestinal ALP could play a critical role in attenuating reactive oxygen species (ROS) generation and ROS facilitating NF-κB pathway-induced systemic inflammation in meat geese. The impacts of IHF and AGF systems on gut microbial composition via 16 sRNA sequencing were assessed in meat geese. The host markers analysis through protein expression of serum and cecal tissues, hematoxylin and eosin (H&E) staining, localization of NF-қB and Nrf2 by immunofluorescence analysis, western blotting analysis of ALP, and quantitative PCR of cecal tissues was evaluated. In the gut microbiota analysis, meat geese supplemented with pasture showed a significant increase in commensal microbial richness and diversity compared to IHF meat geese demonstrating the antimicrobial, antioxidant, and anti-inflammatory ability of the AGF system. A significant increase in intestinal ALP-induced Nrf2 signaling pathway was confirmed representing LPS dephosphorylation mediated TLR4/MyD88 induced ROS reduction mechanisms in AGF meat geese. Further, the correlation analysis of top 44 host markers with gut microbiota showed that artificial pasture intake protected gut barrier functions via reducing ROS-mediated NF-κB pathway-induced gut permeability, systemic inflammation, and aging phenotypes. In conclusion, the intestinal ALP functions to regulate gut microbial homeostasis and barrier function appear to inhibit pro-inflammatory cytokines by reducing LPS-induced ROS production in AGF meat geese. The AGF system may represent a novel therapy to counteract the chronic inflammatory state leading to low dietary fiber-related diseases in animals.

Dietary fibers with low hydration properties exacerbate diarrhea and impair intestinal health and nutrient digestibility in weaned piglets

BackgroundThis study aimed to investigate the hydration properties of different-source fibrous materials by comparing their water-binding capacity (WBC), water swelling capacity (WSC), viscosity, and in vivo effects of selected samples on growth performance, nutrient digestibility, diarrhea, and intestinal health in weaned piglets.MethodsA total of 13 commercially available fibrous materials were first compared in chemical composition and in vitro hydration property. Subsequently, 40 weaned piglets were randomized to five experimental dietary groups (8 piglets per group): control diet (a basal diet without dietary fiber, CON), basal diet supplemented with 5% microcrystalline cellulose (MCC), 5% wheat bran (WB), 5% Moringaoleifera leaf powder (MOLP), or 5% sugar beet pulp (SBP), followed by analyzing their growth performance and diarrhea rate in a 28-d experiment. After the feeding experiment, anaesthetized piglets were killed, and their intestinal and colon content or plasma samples were analyzed in nutrient digestibility, intestinal morphology, intestinal barrier, short-chain fatty acids (SCFAs), and bacterial population.ResultsIn vitro studies showed low hydration properties for WB and MCC, while medium hydration properties for MOLP and SBP. In vivo studies indicated that compared with medium hydration property groups, low hydration property groups showed (1) exacerbated diarrhea, impaired intestinal health, and reduced apparent fecal digestibility of dry matter, gross energy, acid detergent fiber, and neutral detergent fiber; (2) decreased SCFAs concentration and relative levels of Lactobacillus and Bifidobacterium, but increased levels of Escherichia coli and Brachyspira hyodysenteriae in colon contents. Additionally, SBP showed optimal performance in reducing diarrhea and increasing SCFAs production. Correlation analysis revealed a positive correlation of fiber hydration properties with in vitro SCFAs production, and diarrhea index and nutrient digestibility were negatively and positively correlated with SCFAs levels in the colon contents of weaned piglets, respectively.ConclusionsDifferent-source dietary fibers varied in their hydration properties and impacts on diarrhea, microbial composition and SCFAs production in weaned piglets. WB and MCC could exacerbate diarrhea and impair nutrient digestibility, probably because their low hydration properties were detrimental to gut microbial homeostasis and fermentation. Our findings provide new ideas for rational use of fiber resources in weaned piglets.

Female reproductive dysfunctions and the gut microbiota.

The gut microbiome is considered an endocrine organ that can influence distant organs and associated biological pathways. Recent advances suggest that gut microbial homeostasis is essential for reproductive health and that perturbations in the gut microbiota can lead to reproductive pathologies. This review provides an updated overview of the relationship between the gut microbiome and female reproductive diseases. Specifically, we highlight the most recent findings on the gut microbiome in gynecological pathologies including polycystic ovarian syndrome, endometriosis, and endometrial cancer. Most studies revealed associations between altered gut microbial compositions and these reproductive diseases, though few have suggested cause-effect relationships. Future studies should focus on determining the molecular mechanisms underlying associations between gut microbiota and reproductive diseases. Understanding this bidirectional relationship could lead to the development of novel and effective strategies to prevent, diagnose, and treat female reproductive organ-related diseases.

Necrotic Enteritis in Broiler Chickens: A Review on the Pathogen, Pathogenesis, and Prevention.

Clostridium perfringens type A and C are the primary etiological agents associated with necrotic enteritis (NE) in poultry. The predisposing factors implicated in the incidence of NE changes the physical properties of the gut, immunological status of birds, and disrupt the gut microbial homeostasis, causing an over-proliferation of C. perfringens. The principal virulence factors contributing to the pathogenesis of NE are the α-toxin, β-toxin, and NetB toxin. The immune response to NE in poultry is mediated by the Th1 pathway or cytotoxic T-lymphocytes. C. perfringens type A and C are also pathogenic in humans, and hence are of public health significance. C. perfringens intoxications are the third most common bacterial foodborne disease after Salmonella and Campylobacter. The restrictions on the use of antibiotics led to an increased incidence of NE in poultry. Hence, it is essential to develop alternative strategies to keep the prevalence of NE under check. The control strategies rely principally on the positive modulation of host immune response, nutritional manipulation, and pathogen reduction. Current knowledge on the etiology, pathogenesis, predisposing factors, immune response, effect on the gut microbial homeostasis, and preventative strategies of NE in this post-antibiotic era is addressed in this review.

Environmental microplastics exposure decreases antioxidant ability, perturbs gut microbial homeostasis and metabolism in chicken

The widespread presence and accumulation of microplastics (MPs) in organisms has led to their recognition as a major global ecological issue. There is a lot of data on how MPs affect the physiology and behavior of aquatic species, but the effects of MPs on poultry are less understood. Therefore, we aimed to explore the adverse effects and mechanisms of MPs exposure to chicken health. Results indicated that MPs exposure decreased growth performance and antioxidant ability and impaired chickens' intestine, liver, kidney, and spleen. Additionally, the gut microbiota in chickens exposed to MPs showed a significant decrease in alpha diversity, accompanied by significant alternations in taxonomic compositions. Microbial taxonomic investigation indicated that exposure to MPs resulted in a significant increase in the relative proportions of 11 genera and a distinct decline in the relative percentages of 3 phyla and 52 genera. Among decreased bacterial taxa, 11 genera even couldn't be detected in the gut microbiota of chickens exposed to MPs. Metabolomics analysis indicated that 2561 (1190 up-regulated, 1371 down-regulated) differential metabolites were identified, mainly involved in 5 metabolic pathways, including D-amino acid metabolism, ABC transporters, vitamin digestion and absorption, mineral absorption, and histidine metabolism. Taken together, this study indicated that MPs exposure resulted in adverse health outcomes for chickens by disturbing gut microbial homeostasis and intestinal metabolism. This study also provided motivation for environmental agencies worldwide to regulate the application and disposal of plastic products and decrease environmental contamination.

Chenodeoxycholic acid suppresses AML progression through promoting lipid peroxidation via ROS/p38 MAPK/DGAT1 pathway and inhibiting M2 macrophage polarization

PurposeBile acids are steroid synthesized in liver, which are essential for fat emulsification, cholesterol excretion and gut microbial homeostasis. However, the role of bile acids in leukemia progression remains unclear. We aim at exploring the effects and mechanisms of chenodeoxycholic acid (CDCA), a type of bile acids, on acute myeloid leukemia (AML) progression. ResultsHere, we found that CDCA was decreased in feces and plasma of AML patients, positively correlated with the diversity of gut microbiota, and negatively associated with AML prognosis. We further demonstrated that CDCA suppressed AML progression both in vivo and in vitro. Mechanistically, CDCA bound to mitochondria to cause mitochondrial morphology damage containing swelling and reduction of cristae, decreased mitochondrial membrane potential and elevated mitochondrial calcium level, which resulted in the production of excessive reactive oxygen species (ROS). Elevated ROS further activated p38 MAPK signaling pathway, which collaboratively promoted the accumulation of lipid droplets (LDs) through upregulating the expression of the diacylglycerol O-acyltransferase 1 (DGAT1). As the consequence of the abundance of ROS and LDs, lipid peroxidation was enhanced in AML cells. Moreover, we uncovered that CDCA inhibited M2 macrophage polarization and suppressed the proliferation-promoting effects of M2 macrophages on AML cells in co-cultured experiments. ConclusionOur findings demonstrate that CDCA suppresses AML progression through synergistically promoting LDs accumulation and lipid peroxidation via ROS/p38 MAPK/DGAT1 pathway caused by mitochondrial dysfunction in leukemia cells and inhibiting M2 macrophage polarization.

Prebiotic-like cyclodextrin assisted silybin on NAFLD through restoring liver and gut homeostasis.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease with no currently approved treatment. The natural compound silybin (SLN) has versatile hepatoprotective efficacy with negligible adverse effects; however, poor absorption limits its clinical applications. Gut microbiota has been proposed to play a crucial role in the pathophysiology of NAFLD and targeted for disease control. Cyclodextrins, the cyclic oligosaccharides, were documented to have various health benefits with potential prebiotic properties. This study aimed to develop a silybin-2-hydroxypropyl-β-cyclodextrin inclusion (SHβCD) to improve the therapeutic efficacy of SLN and elucidate the mechanisms of improvement. The results showed that SLN formed a 1:1 stoichiometric inclusion complex with HP-β-CD. The solubility of SLN was increased by generating SHβCD, resulting in improved drug permeability and bioavailability. In high-fat diet (HFD)-fed hamsters, SHβCD modulated gut health by restoring the gut microbiota and intestinal integrity. SHβCD showed superior anti-lipid accumulation, antioxidant, and anti-inflammatory effects compared with SLN alone. Transcriptome analysis in the liver tissue implied that the improved inflammation and/or energy homeostasis was the potential mechanism. Therefore, SHβCD may be a promising alternative for the treatment of NAFLD, attributing to the dual functions of HβCD on drug absorption and gut microbial homeostasis.

Targeting Gut Microbiota and Host Metabolism with Dendrobium officinale Dietary Fiber to Prevent Obesity and Improve Glucose Homeostasis in Diet-Induced Obese Mice.

Obesity is becoming a major public health problem due to excess dietary fat intake. Dendrobium officinale (D. officinale) is a medicinefoodhomology plant and exerts multiple health-promoting effects. However, its antiobesity effects and the potential mechanisms remain unclear. High-fat diet (HFD)-fed mice are administered D. officinale dietary fiber (DODF) daily by gavage for 11 weeks. The results show that treatment with DODF alleviates obesity, liver steatosis, inflammation, and oxidant stress in HFD-induced obese mice. Improved glucose homeostasis in obese mice after DODF treatment is achieved by enhancing insulin pathway and hepatic glycogen synthesis. DODF restructures the gut microbiota in obese mice by decreasing the relative abundance of Bilophila and increasing the relative abundances of Akkermansia, Bifidobacterium, and Muribaculum. Also, DODF reshapes the metabolic phenotype of obese mice as indicated by up-regulating energy metabolism, increasing acetate and taurine, and reducing serum low density/very low density lipoproteins (LDL/VLDL). These beneficial effects are partly transferred by FMT, implying the gut microbiota as a target for the protective effect of DODF on obesity-related symptoms. The results suggest that DODF can be used as a novel prebiotics to maintain the gut microbial homeostasis and improve metabolic health, preventing obesity and related metabolic syndrome.