Exploring the effects of environmentally relevant concentrations of tris(2-chloroethyl) phosphate on tadpole health: A comprehensive analysis of intestinal microbiota and hepatic transcriptome.

Tris(2-chloroethyl) phosphate (TCEP), a chlorinated organophosphate ester, is commonly found in aquatic environments. Due to its various toxic effects, it may pose a risk to the health of aquatic organisms. However, the potential impacts of TCEP exposure on the intestinal microbiota and hepatic function in amphibians have not been reported. This study investigated the impact of long-term exposure to environmentally relevant concentrations of TCEP (0, 3, and 90 µg/L) on the intestinal microbiota and hepatic transcriptome of Polypedates megacephalus tadpoles. The results showed that the body size of the tadpoles decreased significantly with an increase in TCEP concentration. Additionally, TCEP exposure affected the diversity and composition of the intestinal microbiota in tadpoles, leading to significant changes in the relative abundance of certain bacterial groups (the genera Aeromonas decreased and Citrobacter increased) and potentially promoting a more even distribution of microbial species, as indicated by a significant increase in the Simpson index. Moreover, the impact of TCEP on hepatic gene expression profiles in tadpoles was significant, with the majority of differentially expressed genes (DEGs) (709 out of 906 total DEGs in 3 µg/L of TCEP versus control, and 344 out of 387 DEGs in 90 µg/L of TCEP versus control) being significantly down-regulated, which were primarily related to immune response and immune system process. Notably, exposure to TCEP significantly reduced the relative abundance of the genera Aeromonas and Cetobacterium in the tadpole intestine. This reduction was positively correlated with the down-regulated expression of immune-related genes in the liver of corresponding tadpoles. In summary, these findings provide empirical evidence of the potential health risks to tadpoles exposed to TCEP at environmentally relevant concentrations.

Effects of dietary salidroside on intestinal health, immune parameters and intestinal microbiota in largemouth bass (Micropterus salmoides).

The largemouth bass has become one of the economically fish in China, according to the latest China Fishery Statistical Yearbook. The farming scale is constantly increasing. Salidroside has been found in past studies to have oxidative stress reducing and immune boosting properties. In this study, the addition of six different levels of salidroside supplements were 0、40、80、120、160 and 200 mg kg-1. A 56-day feeding trial was conducted to investigate the effects of salidroside on the intestinal health, immune parameters and intestinal microbiota composition of largemouth bass. Dietary addition of salidroside significantly affected the Keap-1ß/Nrf-2 pathway as well as significantly increased antioxidant enzyme activities resulting in a significant increase in antioxidant capacity of largemouth bass. Dietary SLR significantly reduced feed coefficients. The genes related to tight junction proteins (Occludin, ZO-1, Claudin-4, Claudin-5) were found to be significantly upregulated in the diet supplemented with salidroside, indicating that salidroside can improve the intestinal barrier function (p < 0.05). The dietary administration of salidroside was found to significantly reduce the transcription levels of intestinal tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) (p < 0.05). Furthermore, salidroside was observed to reduce the transcription levels of intestinal apoptosis factor Bcl-2 associated death promoter (BAD) and recombinant Tumor Protein p53 (P53) (p < 0.05). Concomitantly, the beneficial bacteria, Fusobacteriota and Cetobacterium, was significantly increased in the SLR12 group, while that of pathogenic bacteria, Proteobacteria, was significantly decreased (p < 0.05). In conclusion, the medium-sized largemouth bass optimal dosage of salidroside in the diet is 120mg/kg-1.

Jianpi Jiedu decoction suppresses colorectal cancer growth by inhibiting M2 polarization of TAMs through the tryptophan metabolism-AhR pathway.

BACKGROUND: Traditional Chinese medicine, JianpiJiedu decoction (JPJDF), has been utilized in colorectal cancer (CRC) treatment for over forty years. The potential of JPJDF to inhibit CRC through modulation of intestinal microbiota and their metabolites remains uncertain. AIMS: This study aims to further investigate the therapeutic mechanisms of JPJDF in CRC. METHODS: CAC mouse models were developed using azoxymethane (AOM) and dextran sulfate sodium (DSS). Intestinal tissues and contents underwent 16S rRNA gene sequencing and untargeted metabolomics analysis. Serum levels of IL-1ß and TNF-α were measured using ELISA. Immunohistochemistry was utilized to assess the expression of Ki67, ZO-1, Occludin, CD68, and CD206. Furthermore, western blotting was performed to evaluate the protein expression of AhR and NF-κB. RESULTS: JPJDF inhibited colorectal tumourigenesis in AOM/DSS treated mice, while also suppressing tumor cell proliferation and upregulating the expression of tight junction proteins. The results of 16S rRNA gene sequencing analysis revealed that JPJDF altered intestinal microbiota composition by increasing the abundance of beneficial bacteria. Additionally, JPJDF reduced tryptophan metabolites, effectively alleviating inflammation and significantly restoring intestinal barrier function in CAC mice. Molecular biology experiments confirmed that JPJDF suppressed the expression levels of AhR and M2-type tumor-associated macrophages, thereby promoting anti-tumor immunity and exerting inhibitory effects on CAC growth. CONCLUSION: JPJDF can regulate the tryptophan metabolism-AhR pathway by modulating the gut microbiota, reducing intestinal inflammation, improving intestinal barrier function, enhancing anti-tumor immunity, and effectively inhibiting CAC growth.

Dietary lauric acid promoted antioxidant and immune capacity by improving intestinal structure and microbial population of swimming crab (Portunus trituberculatus).

Lauric acid (LA), a saturated fatty acid with 12 carbon atoms, is widely regarded as a healthy fatty acid that plays an important role in disease resistance and improving immune physiological function. The objective of this study was to determine the effects of dietary lauric acid on the growth performance, antioxidant capacity, non-specific immunity and intestinal microbiology, and evaluate the potential of lauric acids an environmentally friendly additive in swimming crab (Portunus trituberculatus) culture. A total of 192 swimming crabs with an initial body weight of 11.68 ± 0.02 g were fed six different dietary lauric acid levels, the analytical values of lauric acid were 0.09, 0.44, 0.80, 1.00, 1.53, 2.91 mg/g, respectively. There were four replicates per treatment and 8 juvenile swimming crabs per replicate. The results indicated that final weight, percent weight gain, specific growth rate, survival and feed intake were not significantly affected by dietary lauric acid levels; however, crabs fed diets with 0.80 and 1.00 mg/g lauric acid showed the lowest feed efficiency among all treatments. Proximate composition in hepatopancreas and muscle were not significantly affected by dietary lauric acid levels. The highest activities of amylase and lipase in hepatopancreas and intestine were found at crabs fed diet with 0.80 mg/g lauric acid (P<0.05), the activity of carnitine palmityl transferase (CPT) in hepatopancreas and intestine significantly decreased with dietary lauric acid levels increasing from 0.09 to 2.91 mg/g (P<0.05). The lowest concentration of glucose and total protein and the activity of alkaline phosphatase in hemolymph were observed at crabs fed diets with 0.80 and 1.00 mg/g lauric acid among all treatments. The activity of GSH-Px in hepatopancreas significantly increased with dietary lauric acid increasing from 0.09 to 1.53 mg/g, MDA in hepatopancreas and hemolymph was not significantly influenced by dietary lauric acid levels. The highest expression of cat and gpx in hepatopancreas were exhibited in crabs fed diet with 1.00 mg/g lauric acid, however, the expression of genes related to the inflammatory signaling pathway (relish, myd88, traf6, nf-κB ) were up-regulated in the hepatopancreas with dietary lauric acid levels increasing from 0.09 to 1.00 mg/g, moreover, the expression of genes related to intestinal inflammatory, immune and antioxidant were significantly affected by dietary lauric acid levels (P<0.05). Crabs fed diet without lauric acid supplementation exhibited higher lipid drop area in hepatopancreas than those fed the other diets (P<0.05). The expression of genes related to lipid catabolism was up-regulated, however, and the expression of genes related to lipid synthesis was down-regulated in the hepatopancreas of crabs fed with 0.80 mg/g lauric acid. Lauric acid improved hepatic tubular integrity, and enhanced intestinal barrier function by increasing peritrophic membrane (PM) thickness and upregulating the expression of structural factors (per44, zo-1) and intestinal immunity-related genes. In addition, dietary 1.00 mg/g lauric acid significantly improved the microbiota composition of the intestinal, increased the abundance of Actinobacteria and Rhodobacteraceae, and decreased the abundance of Vibrio, thus maintaining the microbiota balance of the intestine. The correlation analysis showed that there was a relationship between intestinal microbiota and immune-antioxidant function. In conclusion, the dietary 1.00 mg/g lauric acid is beneficial to improve the antioxidant capacity and intestinal health of swimming crab.

The diet-intestinal microbiota dynamics and adaptation in an elevational migration bird, the Himalayan bluetail (Tarsiger rufilatus).

Migratory birds experience changes in their environment and diet during seasonal migrations, thus requiring interactions between diet and gut microbes. Understanding the co-evolution of the host and gut microbiota is critical for elucidating the rapid adaptations of avian gut microbiota. However, dynamics of gut microbial adaptations concerning elevational migratory behavior, which is prevalent but understudied in montane birds remain poorly understood. We focused on the Himalayan bluetail (Tarsiger rufilatus) in the montane forests of Mt. Gongga to understand the diet-gut microbial adaptations of elevational migratory birds. Our findings indicate that elevational migratory movements can rapidly alter gut microbial composition and function within a month. There was a significant interaction between an animal-based diet and gut microbiota across migration stages, underscoring the importance of diet in shaping microbial communities. Furthermore, the gut microbial composition of T. rufilatus may be potentially altered by high-altitude acclimatization. An increase in fatty acid and amino acid metabolism was observed in response to low temperatures and limited resources, resulting in enhanced energy extraction and nutrient utilization. Moreover, microbial communities in distinct gut segments varied in relative abundance and responses to environmental changes. While the bird jejunum exhibited greater susceptibility to food and environmental fluctuations, there was no significant difference in metabolic capacity among gut segments. This study provides initial evidence of rapid diet-gut microbial changes in distinct gut segments of elevational migratory birds and highlights the importance of seasonal sample collection. Our findings provide a deeper understanding of the unique high-altitude adaptation patterns of the gut microbiota for montane elevational migratory birds.

Revealing the effect of sea buckthorn oil, fish oil and structured lipid on intestinal microbiota, colonic short chain fatty acid composition and serum lipid profiles in vivo.

In this study, the effects of sea buckthorn oil (SBO), fish oil (FO) and an enzymatically synthesized structured lipid (SL) on serum, short-chain fatty acids (SCFAs) and intestinal microbiota in Sprague-Dawley (SD) rats were investigated. The results demonstrated that FO, SBO, and SL effectively reduced the levels of high-density lipoprotein cholesterol and low-density lipoprotein cholesterol in the serum of SD rats. SBO increased serum triglyceride levels, while FO elevated total cholesterol levels. Furthermore, all three dietary lipids decreased short-chain fatty acid production and enhanced intestinal microbiota diversity. FO increased the abundance of intestinal microbiota including Romboutsia, Lactobacillus, Escherichia-Shigella, and Lachnospiraceae_NK4A136_group. Conversely, all three dietary lipids reduced the abundance of Klebsiella and Blautia. These findings provide a foundation for understanding the functionality of SBO and FO as well as their potential application in synthesizing novel SLs to regulate intestinal microbiota.

Unlocking the therapeutic potential of Huoxiang Zhengqi San in cold and high humidity-induced diarrhea: Insights into intestinal microbiota modulation and digestive enzyme activity.

Huoxiang Zhengqi San (HXZQS), a traditional Chinese herbal formula, enjoys widespread use in Chinese medicine to treat diarrhea with cold-dampness trapped spleen syndrome (CDSS), which is induced by exposure to cold and high humidity stress. This study aimed to explore its therapeutic mechanisms in mice, particularly focusing on the intestinal microbiota. Forty male SPF-grade KM mice were allocated into two groups: the normal control group (H-Cc, n = 10) and the CDSS group (H-Mc, n = 30). After modeling, H-Mc was subdivided into H-Mc (n = 15) and HXZQS treatment (H-Tc, n = 15) groups. Intestinal samples were analyzed for enzyme activity and microbiota composition. Our findings demonstrated a notable reduction in intestinal lactase activity post-HXZQS treatment (P < 0.05). Lactobacillus johnsonii, Lactobacillus reuteri, and Lactobacillus murinus emerged as the main dominant species across most groups. However, in the H-Mc group, Clostridium sensu stricto 1 was identified as the exclusive dominant bacteria. LEfSe analysis highlighted Clostridiales vadinBB60 group and Corynebacterium as differential bacteria in the H-Tc group, and Cyanobacteria unidentified specie in the H-Mc group. Predicted microbiota functions aligned with changes in abundance, notably in cofactors and vitamins metabolism. The collinear results of the intestinal microbiota interaction network showed that HXZQS restored cooperative interactions among rare bacteria by mitigating their mutual promotion. The HXZQS decoction effectively alleviates diarrhea with CDSS by regulating intestinal microbiota, digestive enzyme activity, and microbiota interaction. Notably, it enhances Clostridium vadinBB60 and suppresses Cyanobacteria unidentified specie, warranting further study.

Effects of dietary ginger (Zingiber officinale) polysaccharide on the growth, antioxidant, immunity response, intestinal microbiota, and disease resistance to Aeromonas hydrophila in crucian carp (Carassius auratus).

Ginger polysaccharides (GP) promote growth and development in fish. However, the effects of GP on crucian carp remain unclear. The present study investigated the effects of GP on the growth performance, immunity, intestinal microbiota, and disease resistance in crucian carp. Four treatment groups were established with different concentrations of GP (0.1 %, 0.2 %, 0.4 %, and 0.8 %). GP was not added as the control group, and the feeding period lasted for 56 d, followed by a 96-h anti-infection treatment using Aeromonas hydrophila. The results showed that dietary GP significantly improved growth performance, especially in the 0.4 % GP group. Furthermore, GP administration notably increased serum lysozyme (LMZ) activity, digestive enzyme performance, and antioxidant capacity of crucian carp. Moreover, dietary inclusion of GP up-regulated the expression of tumour necrosis factor-α (TNF-α), interleukin-8 (IL-8), interferon-γ (IFN-γ), and nuclear factor kappa-B (NF-κB) genes while down-regulating IL-10 and transforming growth factor-ß (TGF-ß) gene expressions, thus promoting liver health in crucian carp. Additionally, incorporating GP into the diet regulated both the diversity and composition of the intestinal microbiota in crucian carp, explicitly enhancing the relative abundance of beneficial bacteria, such as Fusobacteriota and Firmicutes. Therefore, GP reduces the mortality of crucian carp infected with A. hydrophila. In conclusion, this study provides novel insights into the application of dietary GP in cultured fish and evaluates the value of traditional Chinese medicinal polysaccharides against pathogenic bacteria.

Modulation of gut microbiota composition and predicted metabolic capacity after nutritional programming with a plant-rich diet in Atlantic salmon (Salmo salar): insights across developmental stages.

To promote sustainable aquaculture, the formulation of Atlantic salmon (Salmo salar) feeds has changed in recent decades, focusing on replacing standard marine-based ingredients with plant-based alternatives, increasingly demonstrating successful outcomes in terms of fish performance. However, little is known about how these plant-based diets may impact the gut microbiota at first feeding and onwards. Nutritional programming (NP) is one strategy applied for exposing fish to a plant-based (V) diet at an early stage in life to promote full utilisation of plant-based ingredients and prevent potential adverse impacts of exposure to a plant-rich diet later in life. We investigated the impact of NP on gut microbiota by introducing fish to plant ingredients (V fish) during first feeding for a brief period of two weeks (stimulus phase) and compared those to fish fed a marine-based diet (M fish). Results demonstrated that V fish not only maintained growth performance at 16 (intermediate phase) and 22 (challenge phase) weeks post first feeding (wpff) when compared to M fish but also modulated gut microbiota. PERMANOVA general effects revealed gut microbiota dissimilarity by fish group (V vs. M fish) and phases (stimulus vs. intermediate vs. challenge). However, no interaction effect of both groups and phases was demonstrated, suggesting a sustained impact of V diet (nutritional history) on fish across time points/phases. Moreover, the V diet exerted a significant cumulative modulatory effect on the Atlantic salmon gut microbiota at 16 wpff that was not demonstrated at two wpff, although both fish groups were fed the M diet at 16 wpff. The nutritional history/dietary regime is the main NP influencing factor, whereas environmental and host factors significantly impacted microbiota composition in M fish. Microbial metabolic reactions of amino acid metabolism were higher in M fish when compared to V fish at two wpff suggesting microbiota played a role in digesting the essential amino acids of M feed. The excessive mucin O-degradation revealed in V fish at two wpff was mitigated in later life stages after NP, suggesting physiological adaptability and tolerance to V diet. Future studies are required to explore more fully how the microbiota functionally contributes to the NP.

Uncovering the mechanism of Clostridium butyricum CBX 2021 to improve pig health based on in vivo and in vitro studies.

Introduction: As a symbiotic probiotic for the host, Clostridium butyricum (CB) has the potential to strengthen the body's immune system and improve intestinal health. However, the probiotic mechanism of CB is not completely understood. The Clostridium butyricum CBX 2021 strain isolated by our team from a health pig independently exhibits strong butyric acid production ability and stress resistance. Therefore, this study comprehensively investigated the efficacy of CBX 2021 in pigs and its mechanism of improving pig health. Methods: In this study, we systematically revealed the probiotic effect and potential mechanism of the strain by using various methods such as microbiome, metabolites and transcriptome through animal experiments in vivo and cell experiments in vitro. Results: Our in vivo study showed that CBX 2021 improved growth indicators such as daily weight gain in weaned piglets and also reduced diarrhea rates. Meanwhile, CBX 2021 significantly increased immunoglobulin levels in piglets, reduced contents of inflammatory factors and improved the intestinal barrier. Subsequently, 16S rRNA sequencing showed that CBX 2021 treatment implanted more butyric acid-producing bacteria (such as Faecalibacterium) in piglets and reduced the number of potentially pathogenic bacteria (like Rikenellaceae RC9_gut_group). With significant changes in the microbial community, CBX 2021 improved tryptophan metabolism and several alkaloids synthesis in piglets. Further in vitro experiments showed that CBX 2021 adhesion directly promoted the proliferation of a porcine intestinal epithelial cell line (IPEC-J2). Moreover, transcriptome analysis revealed that bacterial adhesion increased the expression of intracellular G protein-coupled receptors, inhibited the Notch signaling pathway, and led to a decrease in intracellular pro-inflammatory molecules. Discussion: These results suggest that CBX 2021 may accelerate piglet growth by optimizing the intestinal microbiota, improving metabolic function and enhancing intestinal health.

Metagenomic comparison of intestinal microbiota between normal and liver fibrotic rhesus macaques (Macaca mulatta).

Liver fibrosis is an important pathological process in chronic liver disease and cirrhosis. Recent studies have found a close association between intestinal microbiota and the development of liver fibrosis. To determine whether there are differences in the intestinal microbiota between rhesus macaques with liver fibrosis (MG) and normal rhesus macaques (MN), fecal samples were collected from 8 male MG and 12 male MN. The biological composition of the intestinal microbiota was then detected using 16S rRNA gene sequencing. The results revealed statistically significant differences in ASVs and Chao1 in the alpha-diversity and the beta-diversity of intestinal microbiota between MG and MN. Both groups shared Prevotella and Lactobacillus as common dominant microbiota. However, beneficial bacteria such as Lactobacillus were significantly less abundant in MG (P = 0.02). Predictive functional analysis using PICRUSt2 gene prediction revealed that MG exhibited a higher relative abundance of functions related to substance transport and metabolic pathways. This study may provide insight into further exploration of the mechanisms by which intestinal microbiota affect liver fibrosis and its potential future use in treating liver fibrosis.

Is it time to revise the fighting strategy toward type 2 diabetes? Sex and pollution as new risk factors.

Diabetes mellitus, a metabolic condition affecting around 537 million individuals worldwide, poses significant challenges, particularly among the elderly population. The etiopathogenesis of type 2 diabetes (T2D) depends on a combination of the effects driven by advancing age, genetic background, and lifestyle habits, e.g. overnutrition. These factors influence the development of T2D differently in men and women, with an obvious sexual dimorphism possibly underlying the diverse clinical features of the disease in different sexes. More recently, environmental pollution, estimated to cause 9 million deaths every year, is emerging as a novel risk factor for the development of T2D. Indeed, exposure to atmospheric pollutants such as PM2.5, O3, NO2, and Persistent Organic Pollutants (POP)s, along with their combination and bioaccumulation, is associated with the development of T2D and obesity, with a 15 % excess risk in case of exposure to very high levels of PM2.5. Similar data are available for plasticizer molecules, e.g. bisphenol A and phthalates, emerging endocrine-disrupting chemicals. Even though causality is still debated at this stage, preclinical evidence sustains the ability of multiple pollutants to affect pancreatic function, promote insulin resistance, and alter lipid metabolism, possibly contributing to T2D onset and progression. In addition, preclinical findings suggest a possible role also for plastic itself in the development of T2D. Indeed, pioneeristic studies evidenced that micro- or nanoplastics (MNP)s, particles in the micro- or nano- range, promote cellular damage, senescence, inflammation, and metabolic disturbances, leading to insulin resistance and impaired glucose metabolism in animal and/or in vitro models. Here we synthesize recent knowledge relative to the association between air-related or plastic-derived pollutants and the incidence of T2D, discussing also the possible mechanistic links suggested by the available literature. We then anticipate the need for future studies in the field of candidate therapeutic strategies limiting pollution-induced damage in preclinical models, such as SGLT-2 inhibitors. We finally postulate that future guidelines for T2D prevention should consider pollution and sex an additional risk factors to limit the diabetes pandemic.

Structural characterization of the glucan from Gastrodia elata Blume and its ameliorative effect on DSS-induced colitis in mice.

The polysaccharide glucan was extracted from Gastrodia elata Blume, and its structural characterizations and beneficial effects against acute dextran sulfate sodium (DSS)-induced ulcerative colitis were investigated. The results showed that a polysaccharide GP with a molecular weight of 811.0 kDa was isolated from G. elata Blume. It had a backbone of α-D-1,4-linked glucan with branches of α-d-glucose linked to the C-6 position. GP exhibited protective effects against DSS-induced ulcerative colitis, and reflected in ameliorating weight loss and pathological damages in mice, increasing colon length, inhibiting the expression of inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß), decreasing the levels of inflammatory related proteins NLRP3 and ASC, and elevating the anti-inflammatory cytokine interleukin-10 (IL-10) level in mouse colon tissues. GP supplementation also reinforced the intestinal barrier by promoting the expression of ZO-1, Occludin, and MUC2 of colon tissues, and positively regulated intestinal microbiota. Thus, GP treatment possessed a significant improvement in ulcerative colitis in mice, and it was expected to be developed as a functional food.

Lactococcus lactis MA5 is a potential autochthonous probiotic for nutrient digestibility enhancement and bacterial pathogen inhibition in hybrid catfish (Ictalurus punctatus × I. furcatus).

With the emergence of diseases, the U.S. catfish industry is under challenge. Current trends prefer autochthonous bacteria as potential probiotic candidates owing to their adaptability and capacity to effectively colonize the host's intestine, which can enhance production performance and bolster disease resistance. The objective of this study was to isolate an autochthonous bacterium as probiotic for hybrid catfish. Initially, an analysis of the intestinal microbiota of hybrid catfish reared in earthen ponds was conducted for subsequent probiotic development. Twenty lactic acid bacteria were isolated from the digesta of overperforming catfish, and most of the candidates demonstrated probiotic traits, including proteolytic and lipolytic abilities; antagonistic inhibition of catfish enteric bacterial pathogens, negative haemolytic activity and antibiotic susceptibility. Subsequent to this screening process, an isolate of Lactococcus lactis (MA5) was deemed the most promising probiotic candidate. In silico analyses were conducted, and several potential probiotic functions were predicted, including essential amino acids and vitamin synthesis. Moreover, genes for three bacteriocins, lactococcin A, enterolysin A and sactipeptide BmbF, were identified. Lastly, various protectant media for lyophilization of MA5 were assessed. These findings suggest that Lactococcus lactis MA5 can be an autochthonous probiotic from hybrid catfish, holding promise to be further tested in feeding trials.

Gut Microbiome and colorectal cancer: discovery of bacterial changes with metagenomics application in Turkish population.

BACKGROUND: Colorectal cancer (CRC) is the 3rd most common cancer in the world and colonic carcinogenesis is a multifactorial disease that involves environmental and genetic factors. Gut microbiota plays a critical role in the regulation of intestinal homeostasis. Increasing evidence shows that the gut microbiome plays a role in CRC development and may be a biomarker for early diagnosis. OBJECTIVE: This study aimed to determine the clinical prognostic significance of gut microbiota in CRC patients in the Turkish population by metagenomic analysis and to determine the microbial composition in tumor tissue biopsy samples. METHODS: Tissue biopsies were taken from the participants with sterile forceps during colonoscopy and stored at -80 °C. Then, DNA isolation was performed from the tissue samples and the V3-V4 region of the 16 S rRNA gene was sequenced on the Illumina MiSeq platform. Quality control of the obtained sequence data was performed. Operational taxonomic units (OTUs) were classified according to the Greengenes database. Alpha diversity (Shannon index) and beta diversity (Bray-Curtis distance) analyses were performed. The most common bacterial species in CRC patients and healthy controls were determined and whether there were statistically significant differences between the groups was tested. RESULTS: A total of 40 individuals, 13 CRC patients and 20 healthy control individuals were included in our metagenomic study. The mean age of the patients was 64.83 and BMI was 25.85. In CRC patients, the level of Bacteroidetes at the phylum taxonomy was significantly increased (p = 0.04), the level of Clostridia at the class taxonomy was increased (p = 0.23), and the level of Enterococcus at the genus taxonomy was significantly increased (p = 0.01). When CRC patients were compared with the control group, significant increases were detected in the species of Gemmiger formicilis (p = 0.15), Prevotella copri (p = 0.02) and Ruminococcus bromii (p = 0.001) at the species taxonomy. CONCLUSIONS: Metagenomic analysis of intestinal microbiota composition in CRC patients provides important data for determining the treatment options for these patients. The results of this study suggest that it may be beneficial in terms of early diagnosis, poor prognosis and survival rates in CRC patients. In addition, this metagenomic study is the first study on the colon microbiome associated with CRC mucosa in the Turkish population.

Indigo Naturalis in Inflammatory Bowel Disease: mechanisms of action and insights from clinical trials.

This study investigates the therapeutic potential of Indigo Naturalis (IN) in treating a Inflammatory Bowel Disease (IBD). The objective is to comprehensively examine the effects and pharmacological mechanisms of IN on IBD, assessing its potential as an novel treatment for IBD. Analysis of 11 selected papers is conducted to understand the effects of IN, focusing on compounds like indirubin, isatin, indigo, and tryptanthrin. This study evaluates their impact on Disease Activity Index (DAI) score, colon length, mucosal damage, and macrophage infiltration in Dextran Sulfate Sodium (DSS)-induced colitis mice. Additionally, It investigate into the anti-inflammatory mechanisms, including Aryl hydrocarbon Receptor (AhR) pathway activation, Nuclear Factor kappa B (NF-κB)/nod-like receptor family pyrin domain containing 3 (NLRP3)/Interleukin 1 beta (IL-1ß) inhibition, and modulation of Toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MYD88)/NF-κB and Mitogen Activated Protein Kinase (MAPK) pathways. Immunomodulatory effects on T helper 17 (Th17)/regulatory T cell (Treg cell) balance and Glycogen synthase kinase-3 beta (GSK3-ß) expression are also explored. Furthermore, the study addresses the role of IN in restoring intestinal microbiota diversity, reducing pathogenic bacteria, and increasing beneficial bacteria. The findings reveal that IN, particularly indirubin and indigo, demonstrates significant improvements in DAI score, colon length, mucosal damage, and macrophage infiltration in DSS-induced colitis mice. The anti-inflammatory effects are attributed to the activation of the AhR pathway, inhibition of inflammatory pathways, and modulation of immune responses. These results exhibit the potential of IN in IBD treatment. Notably, the restoration of intestinal microbiota diversity and balance further supports its efficacy. IN emerges as a promising and effective treatment for IBD, demonstrating anti-inflammatory effects and positive outcomes in preclinical studies. However, potential side effects necessitate further investigation for safe therapeutic development. The study underscores the need for future research to explore a broader range of active ingredients in IN to enhance therapeutic efficacy and safety.

Synergistic impacts of antibiotics and heavy metals on Hermetia illucens: Unveiling dynamics in larval gut bacterial communities and microbial metabolites.

Hermetia illucens larvae showcases remarkable bioremediation capabilities for both antibiotics and heavy metal contaminants. However, the distinctions in larval intestinal microbiota arising from the single and combined effects of antibiotics and heavy metals remain poorly elucidated. In this study, we delved into the details of larval intestinal bacterial communities and microbial metabolites when exposed to single and combined contaminants of oxytetracycline (OTC) and hexavalent chromium (Cr(VI)). After conversion, single contaminant-spiked substrate showed 75.5% of OTC degradation and 95.2% of Cr(VI) reductiuon, while combined contaminant-spiked substrate exhibited 71.3% of OTC degradation and 93.4% of Cr(VI) reductiuon. Single and combined effects led to differences in intestinal bacterial communities, mainly reflected in the genera of Enterococcus, Pseudogracilibacillus, Gracilibacillus, Wohlfahrtiimonas, Sporosarcina, Lysinibacillus, and Myroide. Moreover, these effects also induced differences across various categories of microbial metabolites, which categorized into amino acid and its metabolites, benzene and substituted derivatives, carbohydrates and its metabolites, heterocyclic compounds, hormones and hormone-related compounds, nucleotide and its metabolites, and organic acid and its derivatives. In particular, the differences induced OTC was greater than that of Cr(VI), and combined effects increased the complexity of microbial metabolism compared to that of single contaminant. Correlation analysis indicated that the bacterial genera, Preudogracilibacillus, Enterococcus, Sporosarcina, Lysinibacillus, Wohlfahrtiimonas, Ignatzschineria, and Fusobacterium exhibited significant correlation with significant differential metabolites, these might be used as indicators for the resistance and bioremediation of OTC and Cr(VI) contaminants. These findings are conducive to further understanding that the metabolism of intestinal microbiota determines the resistance of Hermetia illucens to antibiotics and heavy metals.

Guava polysaccharides attenuate high fat and STZ-induced hyperglycemia by regulating gut microbiota and arachidonic acid metabolism.

This study investigated the hypoglycemic mechanism of guava polysaccharides (GP) through the gut microbiota (GM) and related metabolites. Our findings demonstrated that GP significantly mitigated high-fat diet- and streptozotocin-induced hyperglycemia, insulin resistance, hyperlipidemia, elevated alanine aminotransferase, high hepatic inflammation levels, and prevented pancreatic atrophy and hepatomegaly. Interestingly, the benefits of GP were attributed to alterations in the GM. GP decreased the ratio of Firmicutes to Bacteroidetes, significantly inhibiting deleterious bacteria, including Uncultured_f_Desulfovibrionaceae, Bilophila, and Desulfovibrio, while promoting the proliferation of probiotic Bifidobacterium and Bacteroides. In addition, GP promoted the generation of short-chain fatty acids. Notably, the arachidonic acid (AA) metabolism pathway was enriched in liver metabolites. GP significantly elevated hepatic AA and 15-hydroxyeicosatetraenoic acid, while reducing prostaglandin E2 and 5- and 12-hydroxyeicosatetraenoic acid. This modulation is accompanied by the downregulation of hepatic cyclooxygenase-1, 12-lipoxygenase, P38, and c-Jun N-terminal kinase mRNA expression, and the upregulation of cytochrome P4502J5 and insulin receptor substrate 1/2 mRNA expression. However, GP antibiotic treatment did not induce significant alterations in FBG and AA levels or gene expression. Overall, our findings suggest that the hypoglycemic effect of GP may be intricately linked to alterations in AA metabolism, which depends on the GM.

Regulating effect of Qifu Yin on intestinal microbiota in mice with memory impairment induced by scopolamine hydrobromide.

ETHNOPHARMACOLOGICAL RELEVANCE: Qifu Yin (QFY) originates from "Jingyue Quanshu · Volume 51 · New Fang Bazhen · Buzhen" a work by Zhang Jingyue, a distinguished Chinese medical practitioner from the Ming Dynasty. QFY is composed of Ginseng Radix et Rhizoma, Rehmanniae Radix Praeparata, Angelicae Sinensis Radix, Atractylodis Macrocephalae Rhizoma, Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle, Ziziphi Spinosae Semen, and Polygalae Radix. QFY is frequently employed to address memory loss and cognitive impairment stemming from vascular dementia, Alzheimer's disease (AD), and related conditions. Our findings indicate that QFY can mitigate nerve cell damage. Moreover, the study explores the impact of QFY on the calcium ion pathway and sphingolipid metabolism in mice with myocardial infarction, presenting a novel perspective on QFY's mechanism in ameliorating myocardial infarction through lipidomics. While this research provides an experimental foundation for the clinical application of QFY, a comprehensive and in-depth analysis of its improvement mechanism remains imperative. AIM OF THE STUDY: To clarify the regulatory mechanism of QFY on intestinal microecology in mice with memory impairment (MI). MATERIAL AND METHODS: The memory impairment mouse model was established by intraperitoneal injection of scopolamine hydrobromide. Kunming (KM) mice were randomly divided into blank group, Ginkgo tablet group (0.276 g/kg), QFY high, medium and low dose groups (17.2 g/kg, 8.6 g/kg, 4.3 g/kg). The effect on memory ability was evaluated by open field and step-down behavioral experiments. The morphological changes of nerve cells in the hippocampus of mice were observed by pathological method. The contents of superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT) and glutathione peroxidase (GSH-Px) in the brain tissue of mice were detected. The expression levels of CREB, Brain-Derived Neurotrophic Factor (BDNF) and Recombinant Amyloid Precursor Protein (APP) in the hippocampus of mice were determined using immunohistochemistry. The expression of N-methyl-D-aspartate receptor (NMDAR) and cAMP response element binding protein (CREB) related factors in the serum of mice was analyzed by ELISA. The levels of apoptosis signal-regulating kinase-1 (ASK1) and c-Jun N-terminal kinase (JNK) mRNA in the hippocampus were detected by quantitative real-time fluorescence polymerase chain reaction (qPCR). The intestinal feces of mice were collected, and the 16 S rDNA technology was used to detect the changes in intestinal microbiota microecological structure of feces in each group. RESULTS: Behavioral experiments showed that the high-dose QFY group exhibited a significant increase in exercise time (P<0.05) and a decrease in diagonal time (P<0.05) compared to the model group. The medium-dose group of QFY showed a reduction in diagonal time (P<0.05). Additionally, the latency time significantly increased in the medium and high-dose groups of QFY (P<0.01). The number of errors in the low, medium and high dose groups was significantly decreased (P<0.05, P<0.01, P<0.01). The nerve cells in the CA1 and CA3 regions of QFY-treated mice demonstrated close arrangement and clear structure. Furthermore, the content of SOD significantly increased (P<0.01) and the content of MDA significantly decreased (P<0.05) in the low and high-dose QFY groups. The content of CAT in the medium-dose group significantly increased (P < 0.05). Immunohistochemical analysis showed a significant reduction in the number of APP expression particles in the CA1 and CA3 regions of all QFY groups. Moreover, BDNF expression significantly increased in the medium and high-dose groups, while CREB expression significantly increased in the low and medium-dose groups of QFY within the CA1 and CA3 regions. Serum analysis revealed significant increases in CREB content in the low, medium, and high dose groups of QFY (P<0.01, P<0.05, P<0.05), and decreases in NMDAR content across all QFY dose groups (P<0.01). PCR analysis showed a significant decrease in the contents of ASK1 and JNK in the medium-dose group (P<0.01). Microecological analysis of intestinal microbiota demonstrated a significant restoration trend in the relative abundance of Fusobacteria, Planctomycetes, and Verrucomicrobia (P<0.01 or P<0.05) at the phylum level in the QFY groups. At the genus level, Akkermansia, Paramuribaculum, Herminiimonas, Erysipelatoclostridium and other genera in the QFY groups showed a significant trend of relative abundance restoration (P<0.01 or P<0.05). CONCLUSION: QFY can improve the memory of MI animals induced by scopolamine hydrobromide by restoring the homeostasis of intestinal microbiota and regulating related indexes in serum and brain tissue.

Embryo injected with Ochratoxin A induced jejunum injury in ducklings by activating the TLR4 signaling pathway: Involvement of intestinal microbiota.

Ochratoxin A (OTA) is a common mycotoxin that causes intestinal injury in humans and various animal species. OTA may lead to intestinal injury in offspring due to the maternal effect. The aim of this study was to investigate the mechanism of embryo injected with OTA induced jejunum injury in ducklings. The results showed that OTA disrupted the jejunum tight junctions in hatching ducklings, and promoted the secretion of inflammatory cytokines. And this inflammatory response was caused by the activation of the TLR4 signaling pathway. Moreover, embryo injected with OTA could cause damage to the intestinal barrier in 21-day-old ducks, characterized by shortened villi, crypt hyperplasia, disrupted intestinal tight junctions, increased level of LPS in the jejunum, activation of the TLR4 signaling pathway, and increased levels of pro-inflammatory cytokines. Meanwhile, OTA induced oxidative stress in the jejunum. And dysbiosis of gut microbiota was mainly characterized by an increased the relative abundance of Bacteroides, Megamonas, Fournierella, and decreased the relative abundance of Alistipes and Weissella. Interestingly, embryo injected with OTA did not induce these changes in the jejunum of antibiotics-treated 21-day-old ducks. In conclusion, embryo injected with OTA induced jejunum injury in ducklings by activating the TLR4 signaling pathway, which involvement of intestinal microbiota.