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Background/objectives: This study investigated the effects of palmitoleic acid (POA) consumption on liver function, intestinal microbiota, and trimethylamine- N -oxide (TMAO) levels in the serum of mice treated with 3% L-carnitine drinking water. The purpose was to highlight the impact of POA on liver injury associated with high L-carnitine intake., Methods: A correlation analysis was carried out. The physiological and biochemical results showed that the administration of POA could alleviate liver injury induced by high L-carnitine ingestion, as reflected by a reduction in liver function indices (ALT, AST, AKP, and TBA activities) and modulation of antioxidant enzyme activities (SOD, GSH-Px, MDA, and RAHFR). The study also monitored the levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Additionally, to assess the impact of POA on intestinal microbiota, we conducted a 16S rRNA high-throughput sequencing analysis., Results: The findings indicated that POA administration resulted in lower levels of TMAO in treated mice. Furthermore, POA could regulate the composition of intestinal microbiota in L-carnitine mice, particularly affecting Bacteroides vulgatus , Parabacteroides distasonis , Alistipes shahii , Lachnospiraceae NK4A136 group, and Parasutterella secunda , which were closely related to liver injury., Conclusions: In summary, POA could repair liver damage caused by high intake of L-carnitine by regulating the distribution of intestinal flora and subsequently decreasing serum TMAO levels.

Cortisone can enter aquatic ecosystems and pose a risk to organisms therein. However, few studies have explored the effects of cortisone on the gut microbiota of aquatic organisms. Here, we exposed zebrafish (Danio rerio) to cortisone at environmentally relevant concentrations (5.0, 50.0, or 500.0 ng L -1 ) for 60 days to explore its toxicological effects and their association with gut microbiota changes. The terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling assay revealed that exposure to 50 ng L -1 cortisone significantly increased the intestinal cell apoptosis rate, 8-hydroxydeoxyguanosine contents, and caspase-3 and caspase-8 activities. Moreover, the transcriptome analysis results demonstrated a notable downregulation in the expression of most differentially expressed genes associated with apoptosis pathways, as well as changes in DNA replication, oxidative stress, and drug metabolism pathways; these results indicated the occurrence of cortisone-induced stress response in zebrafish. Molecular docking analysis revealed that cortisone can bind to caspase-3 through hydrogen bonds and hydrophobic interactions but that no such interactions occur between cortisone and caspase-8. Thus, cortisone may induce oxidative DNA damage and apoptosis by activating caspase-3. Finally, the 16S rRNA sequencing results demonstrated that cortisone significantly affected microbial community structures and functions in the intestinal ecosystem. These changes may indicate gut microbiota response to cortisone-induced intestinal damage and inflammation. In conclusion, the current results clarify the mechanisms underlying intestinal response to cortisone exposure and provide a basis for evaluating the health risks of cortisone in animals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Astragali Radix (AS) is a widely used herb in traditional Chinese medicine, with calycosin as its main isoflavonoid. Our previous study discovered that calycosin triggers host defense peptide (HDP) production in IPEC-J2 cells. The aim of this study is to investigate the alleviation effects of AS total flavone and AS calycosin on growth performance, intestinal immunity, and microflora in weaned piglets. Sixty-four piglets were assigned randomly to 4 treatment groups, (1) CON: the basal diet, (2) P-CON: the basal diet plus antibiotics (1 g/kg), (3) AS-TF: the basal diet plus AS total flavone at 60 mg/day per piglet, (4) AS-CA: the basal diet plus AS calycosin at 30 mg/day per piglet. Each treatment consists of 4 replicates with 4 piglets per replicate. Results showed that treatment with AS-TF and AS-CA enhanced average daily growth and average daily feed intake compared to the CON group ( P < 0.01), while AS-CA significantly reduced the diarrhea rate ( P < 0.05). Both AS-TF and AS-CA significantly increased serum immunoglobulin (Ig) A and IgG levels, with AS-CA further boosting intestinal mucosal secretory IgA levels ( P < 0.05). Histological analysis revealed improvements in the morphology of the jejunum and ileum and goblet cell count by AS-TF and AS-CA ( P < 0.05). Supplementation of AS-TF and AS-CA promoted the expression of several intestinal HDPs ( P < 0.05), and the effect of AS-CA was better than that of AS-TF. In addition, the AS-TF and AS-CA regulated jejunal microbial diversity and composition, with certain differential bacteria genera were showing high correlation with serum cytokines and immunoglobulin levels, suggesting that the intestinal flora affected by AS-TF and AS-CA may contribute to host immunity. Overall, AS CA and AS TF all improved growth performance and health, likely by enhancing nutrition digestibility, serum and intestinal immunity, and intestinal microbial composition. They showed the similar beneficial effect, indicating AS CA appears to be a major compound contributing to the effects of AS TF. This study demonstrated the positive effect of AS flavonoids on weaned piglets and provided a scientific reference for the efficient use of AS products., Competing Interests: Author LD was employed by the company Feed Branch of Beijing Sanyuan Breeding Technology Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Che, Li, Kong, Geng, Wang, Li, Deng, Chen and Wang.)

This study was performed to investigate the effects of potassium diformate (KDF) on growth performance, apparent digestibility of nutrients, serum biochemical indices, and intestinal microflora of Cherry Valley ducks. In total, 144 female healthy 1-day-old Cherry Valley ducks were divided into 3 groups with 6 replicates per group and 8 ducks per replicate according to the principle of similar body weight. The control group was fed a basic diet. In the 2 experimental groups, 0.8% and 1.2% KDF was added to the basic diet, respectively. The trial period was 6 wk and the pretrial period was 3 wk. The final weight and ADG were significantly higher in the 0.8% KDF group than in the control group (P < 0.05). The feed-to-gain ratio was significantly lower in both KDF groups than in the control group (P < 0.05). The apparent digestibility of CP was significantly higher in both KDF groups than in the control group (P < 0.05). The apparent digestibility of calcium was also significantly higher in the 0.8% KDF group (P < 0.05). The serum levels of alkaline phosphatase, cholesterol, and total protein were significantly lower in the 0.8% KDF group than in the control group (P < 0.05), the IgM content was significantly higher (P < 0.05), the low-density lipoprotein cholesterol, triglyceride, and urea levels were significantly lower (P < 0.01), and the glucose level was significantly higher (P < 0.01). The serum total protein level was significantly higher in the 1.2% KDF group than in the control group (P < 0.05). The relative abundance of Firmicutes and Patescibacteria in the gut of ducks was significantly higher in the 0.8% KDF group than in the control group (P < 0.05), the relative abundance of unclassified Erysipelotrichaceae and Lactobacillus was significantly higher (P < 0.01), and the relative abundance of Fusobacteriota was significantly lower (P < 0.05). However, the relative abundance of Firmicutes in the gut of ducks was significantly higher in the 1.2% KDF group than in the control group (P < 0.05). The relative abundance of unclassified Erysipelotrichaceae and Clostridium sensu stricto 1 was significantly higher (P < 0.01), as was the relative abundance of Fusobacteriota and Proteobacteria (P < 0.05). These findings indicate that the addition of 0.8% KDF to the diet can improve the growth performance of Cherry Valley ducks, promote the absorption of nutrients, change the structure of the microflora in the cecum, and increase the relative abundance of dominant bacteria. It was also shown that there was a significant difference between the 0.8% and 1.2% KDF levels which suggest that the safety margin for overdosing is quite low., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The intestinal microbiota interacts with the host and plays an important role in the immune response, digestive physiology, and regulation of body functions. In addition, it is also well documented that the intestinal microbiota of aquatic animals are closely related to their growth rate. However, whether it resulted in different sizes of crayfish in the rice-crayfish coculture model remained vague. Here, we analyzed the intestinal microbiota characteristics of crayfish of three sizes in the same typical rice-crayfish coculture field by high-throughput sequencing technology combined with quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme activity, investigating the relationship between intestinal microbiota in crayfish and water and sediments. The results showed that the dominant intestinal microbiota of crayfish was significantly different between the large size group (BS), normal size group (NS), and small size group (SS), where Bacteroides and Candidatus&#95;Bacilloplasma contributed to the growth of crayfish by facilitating food digestion through cellulolysis, which might be one of the potential factors affecting the difference in sizes. Follow-up experiments confirmed that the activity of lipase (LPS) and protease was higher in BS, and the relative expression of development-related genes, including alpha-amylase (α-AMY), myocyte-specific enhancer factor 2a (MEF2a), glutathione reductase (GR), chitinase (CHI), and ecdysone receptor (EcR), in BS was significantly higher than that in SS. These findings revealed the intestinal microbiota characteristics of crayfish of different sizes and their potential impact on growth, which is valuable for managing and manipulating the intestinal microbiota in crayfish to achieve high productivity in practice. KEY POINTS: • Significant differences in the dominant microflora of BS, NS, and SS in crayfish. • Cellulolysis might be a potential factor affecting different sizes in crayfish. • Adding Bacteroides and Candidatus&#95;Bacilloplasma helped the growth of crayfish., (© 2024. The Author(s).)

Methionine is an important sulfur-containing amino acid. Health effects of both methionine restriction (MR) and methionine supplementation (MS) have been studied. This study aimed to investigate the impact of a high-methionine diet (HMD) (1.64% methionine) on both the gut and liver functions in mice through multi-omic analyses. Hepatic steatosis and compromised gut barrier function were observed in mice fed the HMD. RNA-sequencing (RNA-seq) analysis of liver gene expression patterns revealed the upregulation of lipid synthesis and degradation pathways, cholesterol metabolism and inflammation-related nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway. Metagenomic sequencing of cecal content demonstrated a shift in gut microbial composition with an increased abundance of opportunistic pathogens and gut microbial functions with up-regulated lipopolysaccharide (LPS) biosynthesis in mice fed HMD. Metabolomic study of cecal content showed an altered gut lipid profile and the level of bioactive lipids, including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), palmitoylethanolamide (PEA), linoleoyl ethanolamide (LEA) and arachidonoyl ethanolamide (AEA), that carry anti-inflammatory effects significantly reduced in the gut of mice fed the HMD. Correlation analysis demonstrated that gut microbiota was highly associated with liver and gut functions and gut bioactive lipid content. In conclusion, this study suggested that the HMD exerted negative impacts on both the gut and liver, and an adequate amount of methionine intake should be carefully determined to ensure normal physiological function without causing adverse effects.

Probiotics can regulate gut microbiota and protect against acute alcohol-induced liver injury through the gut-liver axis. However, efficacy is strain-dependent, and their mechanism remains unclear. This study investigated the effect of lactic acid bacteria (LAB), including Lacticaseibacillus paracasei E10 (E10), Lactiplantibacillus plantarum M (M), Lacticaseibacillus rhamnosus LGG (LGG), Lacticaseibacillus paracasei JN-1 (JN-1), and Lacticaseibacillus paracasei JN-8 (JN-8), on the prevention of acute alcoholic liver injury in mice. We found that LAB pretreatment reduced serum alanine transaminase (ALT) and aspartate transaminase (AST) and reduced hepatic total cholesterol (TC) and triglyceride (TG). JN-8 pretreatment exhibited superior efficacy in improving hepatic antioxidation. LGG and JN-8 pretreatment significantly attenuated hepatic and colonic inflammation by decreasing the expression of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) and increasing the expression of interleukin 10 (IL-10). JN-1 and JN-8 pretreatments have better preventive effects than other LAB pretreatment on intestinal barrier dysfunction. In addition, the LAB pretreatment improved gut microbial dysbiosis and bile acid (BA) metabolic abnormality. All of the strains were confirmed to have bile salt deconjugation capacities in vitro , where M and JN-8 displayed higher activities. This study provides new insights into the prevention and mechanism of LAB strains in preventing acute alcoholic liver injury.

Feed efficiency (FE) is essential for pig production, has been reported to be partially explained by gut microbiota. Despite an extensive body of research literature to this topic, studies regarding the regulation of feed efficiency by gut microbiota remain fragmented and mostly confined to disorganized or semi-structured unrestricted texts. Meanwhile, structured databases for microbiota analysis are available, yet they often lack a comprehensive understanding of the associated biological processes. Therefore, we have devised an approach to construct a comprehensive knowledge graph by combining unstructured textual intelligence with structured database information and applied it to investigate the relationship between pig gut microbes and FE. Firstly, we created the pgmReading knowledge base and the domain ontology of pig gut microbiota by annotating, extracting, and integrating semantic information from 157 scientific publications. Secondly, we created the pgmPubtator by utilizing PubTator to expand the semantic information related to microbiota. Thirdly, we created the pgmDatabase by mapping and combining the ADDAGMA, gutMGene, and KEGG databases based on the ontology. These three knowledge bases were integrated to form the Pig Gut Microbial Knowledge Graph (PGMKG). Additionally, we created five biological query cases to validate the performance of PGMKG. These cases not only allow us to identify microbes with the most significant impact on FE but also provide insights into the metabolites produced by these microbes and the associated metabolic pathways. This study introduces PGMKG, mapping key microbes in pig feed efficiency and guiding microbiota-targeted optimization., (© 2024. The Author(s).)

Gallbladder cancer (GBC) is the most common malignant tumor of the biliary system with the worst prognosis. Even after radical surgery, the majority of patients with GBC have difficulty achieving a clinical cure. The risk of tumor recurrence remains more than 65%, and the overall 5-year survival rate is less than 5%. The gut microbiota refers to a variety of microorganisms living in the human intestine, including bacteria, viruses and fungi, which profoundly affect the host state of general health, disease and even cancer. Over the past few decades, substantial evidence has supported that gut microbiota plays a critical role in promoting the progression of GBC. In this review, we summarize the functions, molecular mechanisms and recent advances of the intestinal microbiota in GBC. We focus on the driving role of bacteria in pivotal pathways, such as virulence factors, metabolites derived from intestinal bacteria, chronic inflammatory responses and ecological niche remodeling. Additionally, we emphasize the high level of correlation between viruses and fungi, especially EBV and Candida spp., with GBC. In general, this review not only provides a solid theoretical basis for the close relationship between gut microbiota and GBC but also highlights more potential research directions for further research in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Li, Chen, Li, Geng, Liu and Wu.)

Colorectal cancer (CRC), a major global health concern, may be influenced by dietary protein digestibility impacting gut microbiota and metabolites, which is crucial for cancer therapy effectiveness. This study explored the effects of a casein protein diet (CTL) versus a free amino acid (FAA)-based diet on CRC progression, gut microbiota, and metabolites using carcinogen-induced (AOM/DSS) and spontaneous genetically induced ( Apc Min/+ mice) CRC mouse models. Comprehensive approaches including 16s rRNA gene sequencing, transcriptomics, metabolomics, and immunohistochemistry were utilized. We found that the FAA significantly attenuated CRC progression, evidenced by reduced colonic shortening and histopathological alterations compared to the CTL diet. Notably, the FAA enriched beneficial gut bacteria like Akkermansia and Bacteroides and reversed CRC-associated dysbiosis. Metabolomic analysis highlighted an increase in ornithine cycle metabolites and specific fatty acids, such as Docosapentaenoic acid (DPA), in FAA-fed mice. Transcriptomic analysis revealed that FAA up-regulated Egl-9 family hypoxia inducible factor 3 (Egln 3) and downregulated several cancer-associated pathways including Hippo, mTOR, and Wnt signaling. Additionally, DPA was found to significantly induce EGLN 3 expression in CRC cell lines. These results suggest that FAA modulate gut microbial composition, enhance protective metabolites, improve gut barrier functions, and inhibit carcinogenic pathways.

Given the burgeoning Nyctereutes procyonoides breeding industry and its growing scale, it is imperative to investigate the impact of high-fat diets on the health of these animals. This study involved 30 male Nyctereutes procyonoides of comparable weights (3 kg ±0.5), randomly assigned to either a control group or a high-fat diet group ( n = 15 each). The latter group was fed a mixture of lard and basal diet in a 2:5 ratio, establishing a high-fat diet model in Nyctereutes procyonoides. This diet induced diarrhea and histopathological changes in the Nyctereutes procyonoides. Analysis of the small intestine contents using 16S rRNA sequencing revealed a high-fat diet-induced disruption in the gut microbiota. Specifically, Escherichia-Shigella emerged as the biomarker in the high-fat diet group ( P = 0.049), while Vagococcus was prevalent in the control group ( P = 0.049), indicating a significant increase in harmful bacteria in the high-fat diet group. Furthermore, this disrupted gut flora correlated with inflammation and oxidative stress, as evidenced by marked increases in TNF-α ( P < 0.01), IL-1β ( P < 0.05), and IL-6 ( P < 0.05) levels, measured via q-PCR, Western blot, and oxidative stress assays. In addition, q-PCR analysis revealed significant upregulation of apoptosis and necrosis markers, including Bax, Caspase3, Caspase9, Caspase12, RIPK3, and RIPK1 ( P < 0.01 to P < 0.001), and a concurrent downregulation of the anti-apoptotic gene Bcl-2 ( P < 0.01) in the high-fat diet group, consistent with protein expression trends. These findings suggest that a high-fat diet alters the gut microbiome toward a more harmful bacterial composition, escalating inflammatory responses and intestinal tissue permeability, culminating in intestinal cell apoptosis and necrosis.IMPORTANCEThis study examines the impact of high-fat diets on Nyctereutes procyonoides. Our research established a Nyctereutes procyonoides model on a high-fat diet, revealing significant health impacts, such as diarrhea, histological anomalies, and alterations in the gut microbiota. These findings emphasize the importance of preventing health issues and promoting sustainable industry growth. They highlight the significant impact of diet on gut microbiota and overall animal health., Competing Interests: The authors declare no conflict of interest.

Microplastics (MPs) are ubiquitous environmental contaminants that have negative impacts on health and safety. The gut microbiota plays multiple roles as a newly discovered virtual metabolic organ. The objective of this study was to investigate the potential of MPs to cause liver injury by disrupting the balance of gut microbiota. The results indicated that exposure to MPs resulted in liver damage and disrupted the homeostasis of gut microbiota. MPs significantly reduced the liver organ coefficient, leading to liver cell injury and impaired function. Additionally, there was an increase in the expression of fibril-related proteins, which positively correlated with MPs concentration. Furthermore, MPs increased the relative abundances of Desulfovibrio, Clostridia, Enterorhabdus, Bacteroides, and Gemella while decreasing the abundance of Dubosoella. Different concentrations of MPs exhibited varying effects on specific bacterial groups, however, both concentrations resulted in an increase in pathogenic bacteria and a decrease in beneficial bacteria, as well as alterations in microbial structure. Moreover, MPs induced oxidative stress, inflammation, apoptosis and necrosis in liver cells. The study found that MPs disrupted gut microbiota homeostasis and activated TLR2/NF-κB/NLRP3 pathway in the liver, providing a new insight into the mechanism underlying MPs-induced liver injury. These findings serve as a warning regarding environmental pollution caused by MPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Endometriosis (EMs) is a prevalent gynecological disorder characterized by the growth of uterine tissue outside the uterine cavity, causing debilitating symptoms and infertility. Despite its prevalence, the exact mechanisms behind EMs development remain incompletely understood. This article presents a comprehensive overview of the relationship between gut microbiota imbalance and EMs pathogenesis. Recent research indicates that gut microbiota plays a pivotal role in various aspects of EMs, including immune regulation, generation of inflammatory factors, angiopoietin release, hormonal regulation, and endotoxin production. Dysbiosis of gut microbiota can disrupt immune responses, leading to inflammation and impaired immune clearance of endometrial fragments, resulting in the development of endometriotic lesions. The dysregulated microbiota can contribute to the release of lipopolysaccharide (LPS), triggering chronic inflammation and promoting ectopic endometrial adhesion, invasion, and angiogenesis. Furthermore, gut microbiota involvement in estrogen metabolism affects estrogen levels, which are directly related to EMs development. The review also highlights the potential of gut microbiota as a diagnostic tool and therapeutic target for EMs. Interventions such as fecal microbiota transplantation (FMT) and the use of gut microbiota preparations have demonstrated promising effects in reducing EMs symptoms. Despite the progress made, further research is needed to unravel the intricate interactions between gut microbiota and EMs, paving the way for more effective prevention and treatment strategies for this challenging condition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tang, Deng, Xu, Yang, Ji, Hao, Wang, Tian, Geng and Miao.)

Juice fermented with lactic acid bacteria (LAB) has received attention due to its health benefits, such as antioxidant and anti-inflammatory. Previous research on LAB-fermented goji juice mainly focused on exploring the changes in the metabolite profile and antioxidant activity in vitro , whereas the liver protection properties of LAB-fermented goji juice in vivo are still unknown. This study aimed to investigate the effects of Lacticaseibacillus paracasei E10-fermented goji juice (E10F), Lactiplantibacillus plantarum M-fermented goji juice (MF), Lacticaseibacillus rhamnosus LGG-fermented goji juice (LGGF) on preventing acute alcoholic liver injury with physiology, gut microbial, and metabolic profiles in mice. Compared with goji juice, E10F, MF, and LGGF enhanced the protective effect against liver injury by reducing serum alanine transaminase (ALT) levels, improving the hepatic glutathione (GSH) antioxidant system, and attenuating inflammation by decreasing the levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β. Furthermore, E10F, MF, and LGGF increased intestinal integrity, restructured the gut microbiota including Bacteroides and Lactobacillus , and altered gut microbial metabolites including kyotorphin, indolelactic acid, and N -methylserotonin. Pretreatment of different LAB-fermented goji juice in mice showed significant differences in gut microbiota and metabolism. The correlation analysis demonstrated that the increase of Lactobacillus , indolelactic acid, and N -methylserotonin by E10F, MF, and LGGF was positively correlated with reduced inflammation and improved liver and gut function. Taken together, E10F, MF, and LGGF all have the potential to be converted into dietary interventions to combat acute alcoholic liver injury. It provided a reference for the study of the hepatoprotective effect of LAB-fermented goji juice.

Diet is a key player in gut-liver axis. However, the effect of different dietary patterns on gut microbiota and liver functions remains unclear. Here, we used rodent standard chow and purified diet to mimic two common human dietary patterns: grain and plant-based diet and refined-food-based diet, respectively and explored their impacts on gut microbiota and liver. Gut microbiota experienced a great shift with notable increase in Desulfovibrio , gut bile acid (BA) levels elevated significantly, and liver inflammation was observed in mice fed with the purified diet. Liver inflammation and elevated gut BA levels also occurred in mice fed with the chow diet after receiving Desulfovibrio desulfuricans ATCC 29,577 (DSV). Restriction of sulfur-containing amino acids (SAAs) prevented liver injury mainly through higher hepatic antioxidant and detoxifying ability and reversed the elevated BA levels due to excess Desulfovibrio . Ex vivo fermentation of human fecal microbiota with primary BAs demonstrated that DSV enhanced production of secondary BAs. Higher concentration of both primary and secondary BAs were found in the gut of germ-free mice after receiving DSV. In conclusion, Restriction of SAAs in diet may become an effective dietary intervention to prevent liver injury associated with excess Desulfovibrio in the gut.

Metformin (Met), a first-line management for type 2 diabetes mellitus, has been expansively employed and studied with results indicating its therapeutic potential extending beyond glycemic control. Beyond its established role, this therapeutic drug demonstrates a broad spectrum of action encompassing over 60 disorders, encompassing metabolic conditions, inflammatory disorders, carcinomas, cardiovascular diseases, and cerebrovascular pathologies. There is clear evidence of Met's action targeting specific nodes in the molecular pathways of these diseases and, intriguingly, interactions with the intestinal microbiota and epigenetic processes have been explored. Furthermore, novel Met derivatives with structural modifications tailored to diverse diseases have been synthesized and assessed. This manuscript proffers a comprehensive thematic review of the diseases amenable to Met treatment, elucidates their molecular mechanisms, and employs informatics technology to prospect future therapeutic applications of Met. These data and insights gleaned considerably contribute to enriching our understanding and appreciation of Met's far-reaching clinical potential and therapeutic applicability., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Pingchuan formula is a traditional Chinese herbal prescription for asthma, but its components and underlying mechanisms remain unclear. Here, we evaluated its anti-asthmatic actvity and regulatory effects on the gut microbiota in mice based on the traditional Chinese medicine Zang-Fu theory, which proposed the exterior-interior relationship between the lung and the large intestine., Methods: Mouse model withovalbumin (OVA)-induced asthma was used to assess the protective effect of the water extract of Pingchuan formula (PC). The chemical compounds of PC and mouse serum metabolites were identified by Ultraperformance liquid chromatography-Q Exactive HF-X spectrometry. Gut microbiota was evaluated by 16 S rRNA gene sequencing. The gut microbiota was depleted with a broad-spectrum antibiotic mixture (Abx) to explore whether it plays a role in the protective effects of PC., Results: PC mainly contains phenols, flavonoids, alkaloids, carboxylic acids, and their derivatives. PC attenuated OVA-induced asthma in mice by alleviating inflammatory infiltration, indicated by decreased levels of IL-18, IL-6, IL-4, and Eotaxin in lung tissues. PC treatment altered the serum metabolites and affected the pyrimidine pathway. In addition, our results showed that acacetin and abscisic acid were the key serum metabolites PC treatment changed the composition of gut microbiota by increasing the relative abundance of Clostridia&#95;UCG&#95;014 and Akkermansia while decreasing Blautia, Barnesiella, and Clostridium&#95;Ⅲ at the genus level. Importantly, the Abx treatment partly abolished the anti-asthmatic effect of PC., Conclusion: We demonstrated that PC could alleviate OVA-induced asthma in mice and protect against inflammatory infiltration in lungs via modulating the serum metabolites and gut microbiota, thereby providing a new reference for the therapeutic effect of PC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Propolis is a traditional natural medicine with various activities such as antioxidant and anti-inflammatory, immunomodulatory, anti-tumour, gastroenteritis treatment and prevention, anti-microbial and parasitic, as well as glucose regulation and anti-diabetes, and is expected to be an anti-diabetic candidate with few side effects, but the mechanism of action of propolis on type 2 diabetes mellitus (T2DM) has not been fully elucidated., Aim of the Study: The purpose of this study was to investigate the mechanism of the effect of ethanol extract of propolis (EEP) on the regulation of blood glucose in T2DM mice., Materials and Methods: We studied the possible mechanism of EEP on T2DM using an animal model of T2DM induced by a combination of a high-fat diet and intraperitoneal injection of streptozotocin (STZ). The experiment was divided into four groups, namely, the normal group (HC), model group (T2DM), EEP and metformin group (MET). Biochemical indexes and cytokines were measured, and the differences of metabolites in the serum were compared by 1 H-NMR. In addition, the diversity of intestinal flora in feces was studied by 16S rDNA amplicon sequencing., Results: The results showed that following treatment with EEP and MET, the weight-loss trend of mice was alleviated, and the fasting blood glucose, insulin secretion level, insulin resistance index, C peptide level and oral glucose tolerance level decreased, whereas the insulin sensitivity index increased, thereby EEP effectively alleviated the occurrence of T2DM and insulin resistance. Compared with the T2DM group, the concentrations of pro-inflammatory cytokines interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) decreased significantly in EEP and MET groups, whereas the concentrations of anti-inflammatory cytokine interleukin-10 (IL-10) increased significantly. Metabolomics results revealed that EEP and MET regulate carbohydrate metabolism and restore amino acid and lipid metabolism. Correlation analysis of intestinal flora in mouse feces showed that compared with the HC group, harmful bacteria such as Bilophila, Eubacterium&#95;ventriosum&#95;group, Mucispirillum and Desulfovibrio were found in the T2DM group, whereas the abundance of beneficial bacteria such as Lactobacillus was significantly reduced. Parabacteroides, Akkermansia, Leuconostoc, and Alloprevotella were abundantly present in the EEP group; however, the MET group showed an increase in the genus Parasutterella, which could regulate energy metabolism and insulin sensitivity., Conclusions: The results showed that EEP and MET reduce fasting blood glucose in T2DM mice, followed by alleviating insulin resistance, improving the inflammatory reaction of mice, regulating the metabolism of mice, and affecting the steady state of gut microbiota. However, the overall therapeutic effect of EEP is better than that of MET., Competing Interests: Declaration of competing interest On behalf of all authors, the corresponding author states that there is no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Liver fibrosis is associated with gut dysbiosis. Metformin administration has emerged as a promising method for the treatment of organ fibrosis. We aimed to investigate whether metformin ameliorates liver fibrosis by enhancing the gut microbiota in mice with carbon tetrachloride (CCl 4 )-induced liver fibrosis and the underlying mechanism., Materials and Methods: A liver fibrosis mouse model was established, and the therapeutic effects of metformin were observed. We administered antibiotic treatment and performed fecal microbiota transplantation (FMT), and 16S rRNA-based microbiome analysis to evaluate the effects of the gut microbiome on metformin-treated liver fibrosis. We isolated the bacterial strain preferably enriched by metformin and assessed its antifibrotic effects., Results: Metformin treatment repaired the gut integrity of the CCl 4 -treated mice. It reduced the number of bacteria in colon tissues and reduced the portal vein lipopolysaccharide (LPS) levels. The FMT performed on the metformin-treated CCl 4 mice alleviated their liver fibrosis and reduced their portal vein LPS levels. The markedly changed gut microbiota was screened out from the feces and named Lactobacillus sp. MF-1 (L. sp. MF-1). In the CCl 4 -treated mice, daily gavage of L. sp. MF-1 maintained gut integrity, inhibited bacterial translocation, and reduced liver fibrosis. Mechanistically, metformin or L. sp. MF-1 inhibited the apoptosis of intestinal epithelial cells and restored CD3 + intestinal intraepithelial lymphocytes in the ileum and CD4 + Foxp3 + lamina propria lymphocytes in the colon., Conclusions: Metformin and its enriched L. sp. MF-1 can reinforce the intestinal barrier to alleviate liver fibrosis by restoring immune function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Gut microbiota plays a crucial role in modulating pig development and health, and gut microbiota characteristics are associated with differences in feed efficiency. To answer open questions in feed efficiency analysis, biologists seek to retrieve information across multiple heterogeneous data sources. However, this is error-prone and time-consuming work since the queries can involve a sequence of multiple sub-queries over several databases. We present an implementation of an ontology-based Swine Gut Microbiota Federated Query Platform (SGMFQP) that provides a convenient, automated, and efficient query service about swine feeding and gut microbiota. The system is constructed based on a domain-specific Swine Gut Microbiota Ontology (SGMO), which facilitates the construction of queries independent of the actual organization of the data in the individual sources. This process is supported by a template-based query interface. A Datalog + -based federated query engine transforms the queries into sub-queries tailored for each individual data source, and an automated workflow orchestration mechanism executes the queries in each source database and consolidates the results. The efficiency of the system is demonstrated on several swine feeding scenarios., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Ulcerative colitis (UC), one of the typical inflammatory bowel diseases caused by dysregulated immunity, still requires novel therapeutic medicine with high efficacy and low toxicity. Hericium erinaceus has been widely used to treat different health problems especially gastrointestinal sickness in China for thousands of years. Here, we isolated, purified, and characterized a novel low weight polysaccharide (HEP10, Mw: 9.9 kDa) from the mycelia of H. erinaceus in submerged culture. We explored the therapeutic effect of HEP10 on UC and explored its underlying mechanisms. On one hand, HEP10 suppressed the production of TNF-α, IL-1β, IL-6, inducible iNOS, and COX-2 in LPS challenged murine macrophage RAW264.7 cells, as well as in colons from DSS-induced colitis mice. On the other hand, HEP10 treatment markedly suppressed the activation of NLRP3 inflammasome, NF-κB, AKT, and MAPK pathways. Moreover, HEP10 reversed DSS-induced alternation of the gut community composition and structure by significantly increasing Akkermansia muciniphila and also promoting functional shifts in gut microbiota. Structural equation modeling also highlighted that HEP10 can change widely through gut microbiota. In conclusion, HEP10 has a better prebiotic effect than the crude polysaccharides of H. erinaceus , which can be used as a novel dietary supplement and prebiotic to ameliorate colitis.

Ferric citrate (FC) has been used as an iron fortifier and nutritional supplement, which is reported to induce colitis in rats, however the underlying mechanism remains to be elucidated. We performed a 16-week study of FC in male healthy C57BL/6 mice (nine-month-old) with oral administration of Ctr (0.9 % NaCl), 1.25 % FC (71 mg/kg/bw), 2.5 % FC (143 mg/kg/bw) and 5 % FC (286 mg/kg/bw). FC-exposure resulted in colon iron accumulation, histological alteration and reduce antioxidant enzyme activities, such as glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and total antioxidant capacity (T-AOC), together with enhanced lipid peroxidation level, including malondialdehyde (MDA) level and 4-Hydroxynonenal (4-HNE) protein expression. Exposure to FC was associated with upregulated levels of the interleukin (IL)- 6, IL-1β, IL-18, IL-8 and tumor necrosis factor α (TNF-α), while down-regulated levels of IL-4 and IL-10. Exposure to FC was positively associated with the mRNA and protein expressions of cysteine-aspartic proteases (Caspase)- 9, Caspase-3, Bcl-2-associated X protein (Bax), while negatively associated with B-cell lymphoma 2 (Bcl2) in mitochondrial apoptosis signaling pathway. FC-exposure changed the diversity and composition of gut microbes. Additionally, the serum lipopolysaccharide (LPS) contents increased in FC-exposed groups when compared with the control group, while the expression of colonic tight junction proteins (TJPs), such as Claudin-1 and Occludin were decreased. These findings indicate that the colonic mucosal injury induced by FC-exposure are associated with oxidative stress generation, inflammation response and cell apoptosis, as well as the changes in gut microbes diversity and composition., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: A high-fat diet (HFD) induces gut microbiota (GM) disorders, leading to intestinal barrier dysfunction and inflammation. Ferulic acid (FA) has shown anti-obesity effects, e.g., reducing body weight and food intake. However, the mechanism linking the anti-obesity effects of FA and GM modulation remains obscure. The present study aimed to clarify the mechanism underlying the anti-obesity effects of FA and modulation of the GM., Methods: C57BL/6 J mice were fed by a low-fat diet (LFD) and HFD with or without FA at a dose of 100 mg/kg of body weight by oral gavage for 12 weeks. Using high-throughput sequencing, gas chromatography, real-time fluorescence quantitative PCR and immunohistochemical staining, the attenuation of obesity by FA were assessed via intestinal barrier integrity, inflammation, and the GM., Results: FA reduced weight gain, improved HFD-induced GM imbalance, significantly enhanced intestinal short-chain fatty acid (SCFA)-producing bacteria (e.g., Olsenella, Eisenbergiella, Dubosiella, Clostridiales&#95;unclassified, and Faecalibaculum) along with SCFA accumulation and its receptors' expression, decreased endotoxin-producing bacteria or obesity-related bacterial genera, and serum endotoxin (lipopolysaccharides), and inhibited the colonic TLR4/NF-κB pathway. Thus, FA can mitigate colonic barrier dysfunction and intestinal inflammation, induce the production of SCFAs and inhibit endotoxins by modulating the GM., Conclusion: These results indicate that enhancement of intestinal barrier by altering the GM may be an anti-obesity target of FA and that FA can be used as a functional compound with great developmental values., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Paecilomyces hepiali , a fungal strain isolated from natural Ophiocordyceps sinensis , contains similar pharmacologically active components, has been used widely as a substitute of O. sinensis in functional food and medicine. However, the components and anti-fatigue effects of P.hepiali spores and their mechanisms of action are largely unknown. Here, we compared the chemical composition in P.hepiali spore (HPS) and mycelium (HPM) by liquid chromatography with tandem mass spectrometry analysis. We found 85 metabolites with significant differences, and HPS contains more L-Malic acid, Oxalacetic acid, Fructose-1,6-bisphosphate, and L-Arginine than HPM. Then we evaluated their anti-fatigue effects and regulatory effects on the gut microbiota in mice. The forced swimming time (SW) was only significantly increased in HPS groups: the high and low dose of the HPS group was 101% and 72% longer than the control group, respectively. Both HPS and HPM treatment decreased lactic acid, blood urea nitrogen, creatine kinase while increased lactate dehydrogenase (LDH) levels in the blood. Moreover, mice treated with HPS and HPM showed less skeletal muscle fiber spacing and breakage. The relative abundance of Alistips , Eubacterium , Bacterium , Parasutterella , and Olsenella in the gut microbiota of the HPS group was higher than that in the HPM group through 16S rRNA gene sequencing analysis. These changes may be related to the regulation of nucleotide, amino acid, and carbohydrate metabolism. Correlation analysis between the gut microbiota and fatigue-related indicators suggested that Alistips , Clostridium , Akkermansia , Olsenella , and Lactobacillus were positively correlated with the SW and LDH content. Our findings demonstrated that HPS has beneficial anti-fatigue effects by regulating gut microbiota.

Polycystic ovary syndrome (PCOS) is a common disease, affecting 8%-13% of the females of reproductive age, thereby compromising their fertility and long-term health. However, the pathogenesis of PCOS is still unclear. It is not only a reproductive endocrine disease, dominated by hyperandrogenemia, but also is accompanied by different degrees of metabolic abnormalities and insulin resistance. With a deeper understanding of its pathogenesis, more small metabolic molecules, such as bile acids, amino acids, and short-chain fatty acids, have been reported to be involved in the pathological process of PCOS. Recently, the critical role of gut microbiota in metabolism has been focused on. The gut microbiota-related metabolic pathways can significantly affect inflammation levels, insulin signaling, glucose metabolism, lipid metabolism, and hormonal secretions. Although the abnormalities in gut microbiota and metabolites might not be the initial factors of PCOS, they may have a significant role in the pathological process of PCOS. The dysbiosis of gut microbiota and disturbance of gut metabolites can affect the progression of PCOS. Meanwhile, PCOS itself can adversely affect the function of gut, thereby contributing to the aggravation of the disease. Inhibiting this vicious cycle might alleviate the symptoms of PCOS. However, the role of gut microbiota in PCOS has not been fully explored yet. This review aims to summarize the potential effects and modulative mechanisms of the gut metabolites on PCOS and suggests its potential intervention targets, thus providing more possible treatment options for PCOS in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Hu, Huang, Zhou, Li, Liu, Geng, Dong, Ma, Song and Song.)

As a common conditional pathogenic bacterium in nature, C. freundii has posed a threat to crayfish culture and may infect humans through consumption. However, the pathogenic mechanism of C. freundii in crayfish remains unknown, which poses difficulties for the prevention and control of the bacterium. In this study, the effects of C. freundii on the digestive organs, intestine and hepatopancreas, of crayfish were investigated by high-throughput sequencing technology combined with histological analysis and flow cytometry. The findings suggested that C. freundii caused disruption of the intestinal microbiota, leading to intestinal inflammation and disrupting intestinal integrity. Meanwhile, C. freundii infection stimulates bile acid biosynthesis in the intestinal microbiota. Transcriptomic results showed significant upregulation of hepatopancreatic lipid degradation pathway and cytochrome P450-related pathways. Follow-up experiments confirmed a decrease in intracellular lipids and an increase in ROS and apoptosis. All the results indicated the disruption of intestinal-liver axis homeostasis due to disturbed intestinal microbiota may as a potential basis for C. freundii pathopoiesis in crayfish. These results provide new insights into the pathogenic molecular mechanisms of C. freundii in the infection of crayfish., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Wang, Deng, Li, Huang, Chen, Ouyang, Geng, Yang, Yin, Luo and Jiang.)

Enterococcus faecium ( E. faecium ) is a protective role that has crucial beneficial functions on intestinal homeostasis. This study aimed to investigate the effects of E. faecium on the laying performance, egg quality, host metabolism, intestinal mucosal immunity, and gut microbiota of laying hens under the Salmonella Enteritidis ( S. Enteritidis ) challenge. A total of 400 45-week-old laying hens were randomly divided into four treatments (CON, EF, SCON, and SEF groups) with five replicates for each group and 20 hens per replicate and fed with a basal diet or a basal diet supplemented with E. faecium (2.5 × 10 8 cfu/g feed). The experiment comprised two phases, consisting of the pre-salmonella challenged phase (from day 14 to day 21) and the post-salmonella challenged phase (from day 21 to day 42). At day 21 and day 22, the hens in SCON and SEF groups were orally challenged with 1.0 ml suspension of 10 9 cfu/ml S. Enteritidis (CVCC3377) daily, whereas the hens in CON and EF groups received the same volume of sterile PBS. Herein, our results showed that E. faecium administration significantly improved egg production and shell thickness during salmonella infection. Also, E. faecium affected host lipid metabolism parameters via downregulating the concentration of serum triglycerides, inhibited oxidative stress, and enhanced immune functions by downregulating the level of serum malondialdehyde and upregulating the level of serum immunoglobulin G. Of note, E. faecium supplementation dramatically alleviated intestinal villi structure injury and crypt atrophy, and improved intestinal mucosal barrier injuries caused by S. Enteritidis challenge. Moreover, our data revealed that E. faecium supplementation ameliorated S. Enteritidis infection-induced gut microbial dysbiosis by altering the gut microbial composition (reducing Bacteroides , Desulfovibrio , Synergistes , and Sutterella , and increasing Barnesiella , Butyricimonas , Bilophila , and Candidatus&#95;Soleaferrea ), and modulating the gut microbial function, such as cysteine and methionine metabolism, pyruvate metabolism, fatty acid metabolism, tryptophan metabolism, salmonella infection, and the PI3K-Akt signaling pathway. Taken together, E. faecium has a strong capacity to inhibit the S. Enteritidis colonization of hens. The results highlight the potential of E. faecium supplementation as a dietary supplement to combat S. Enteritidis infection in animal production and to promote food safety., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Rong, Liu, Liang, Geng, Wang, Zhang, Ji, Zhao and Ma.)

Pelvic radiotherapy is the key treatment for pelvic malignancies, usually including pelvic primary tumour lesions and lymphatic drainage areas in the pelvic region. Therefore, the intestinal tract in the radiation field is inevitably damaged, a phenomenon clinically referred to as radiation enteritis, and diarrhoea is the most common clinical symptom of radiation enteritis. Therefore, it is necessary to study the mechanism of radiation-induced diarrhoea. It has been found that the gut microbiome plays an important role in the development of diarrhoea in response to pelvic radiotherapy, and the species and distribution of intestinal microbiota are significantly altered in patients after pelvic radiotherapy. In this study, we searched for articles indexed in the Cochrane Library, Web of Science, EMBASE and PubMed databases in English and CNKI, Wanfang data and SINOMED in Chinese from their inception dates through 13 March 2020 to collect studies on the gut microbiome in pelvic radiotherapy patients. Eventually, we included eight studies: one study report on prostatic carcinoma, five studies on gynaecological carcinoma and two papers on pelvic carcinomas. All studies were designed as self-controlled studies, except for one that compared toxicity to nontoxicity. The results from all the studies showed that the diversity of intestinal flora decreased during and after pelvic radiotherapy, and the diversity of intestinal flora decreased significantly in patients with diarrhoea after radiotherapy. Five studies observed that the community composition of the gut microbiota changed at the phylum, order or genus level before, during, and after pelvic radiotherapy at different time points. In addition, the composition of the gut microbiota before radiotherapy was different between patients with postradiotherapy diarrhoea and those without diarrhoea in five studies. However, relevant studies have not reached consistent results regarding the changes in microbiota composition. Changes in the intestinal flora induced by pelvic radiotherapy and their relationship between changes in intestinal flora and the occurrence of radiation-induced diarrhoea (RID) are discussed in this study, providing a theoretical basis for the causes of RID after pelvic radiotherapy., (© 2021. The Author(s).)

Pinus yunnanensis pollen is rich in various physiological functions. However, whether the pine pollen wall (PW) plays a beneficial role in the body has not been studied. In this work, we have analyzed its effects on the metabolism and gut microbiota of mouse models of dyslipidemia. We found that the intake of pine PW prevents the liver pathologic changes and reduce the concentrations of TNF-α, IL-6, TC, and high-density lipoprotein cholesterol. Moreover, it can regulate bile acid and fat metabolism, SCFAs content, and the structure of the gut microbiota. According to the change of carbohydrate metabolites, we speculated that cellulose should be the main component to play the above beneficial role, and sporopollenin cannot be utilized in the intestine. Therefore, we consider this study of great significance as it gives a description of biological effects of the pine PW and paves the road to its use in health products., (© 2020 John Wiley & Sons Ltd.)

Duck-origin parvovirus disease is an epidemic disease mainly caused by duck-origin goose parvovirus (D-GPV), which is characterized by beak atrophy and dwarfism syndrome. Its main symptoms are persistent diarrhea, skeletal dysplasia, and growth retardation. However, the pathogenesis of Cherry Valley ducks infected by D-GPV has not been studied thoroughly. To perceive the distribution of D-GPV in the intestinal tract, intestinal morphological development, intestinal permeability, inflammatory cytokines in Cherry Valley ducks, and expression of tight junction protein, the D-GPV infection was given intramuscularly. Illumina MiSeq sequencing technology was used to analyze the diversity and structure of ileum flora and content of short-chain fatty acids of its metabolites. To investigate the relationship between intestinal flora changes and intestinal barrier function after D-GPV infection on Cherry Valley ducks is of great theoretical and practical significance for further understanding the pathogenesis of D-GPV and the structure of intestinal flora in ducks. The results showed that D-GPV infection was accompanied by intestinal inflammation and barrier dysfunction. At this time, the decrease of a large number of beneficial bacteria and the content of short-chain fatty acids in intestinal flora led to the weakening of colonization resistance of the intestinal flora and the accumulation of potentially pathogenic bacteria, which would aggravate the negative effect of D-GPV damage to the intestinal tract. Furthermore, a significant increase in Unclassified&#95;S24-7 and decrease in Streptococcus was observed in D-GPV persistent, indicating the disruption in the structure of gut microbiota. Notably, the shift of microbiota was associated with the transcription of tight-junction protein and immune-associated cytokines. These results indicate that altered ileum microbiota, intestinal barrier, and immune dysfunction are associated with D-GPV infection. Therefore, there is a relationship between the intestinal barrier dysfunction and dysbiosis caused by D-GPV, but the specific mechanism needs to be further explored., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Hericium erinaceus ( H. erinaceus ) is widely studied as a medicinal and edible fungus. Recent studies have shown that H. erinaceus has protective effects for diseases, such as inflammatory bowel disease and cancer, which are related to gut microbiota. To investigate the benefits of H. erinaceus intake on gut microbiota and blood indices in adulthood, we recruited 13 healthy adults to consume H. erinaceus powder as a dietary supplement. Blood changes due to H. erinaceus consumption were determined by routine hematological examination and characterized by serum biochemical markers. Microbiota composition was profiled by 16S ribosomal RNA gene sequencing. Results showed that daily H. erinaceus supplementation increased the alpha diversity within the gut microbiota community, upregulated the relative abundance of some short-chain fatty acid (SCFA) producing bacteria ( Kineothrix alysoides , Gemmiger formicilis , Fusicatenibacter saccharivorans , Eubacterium rectale , Faecalibacterium prausnitzii ), and downregulated some pathobionts ( Streptococcus thermophilus , Bacteroides caccae , Romboutsia timonensis ). Changes within the gut microbiota were correlated with blood chemical indices including alkaline phosphatase (ALP), low-density lipoprotein (LDL), uric acid (UA), and creatinine (CREA). Thus, we found that the gut microbiota alterations may be part of physiological adaptations to a seven-day H. erinaceus supplementation, potentially influencing beneficial health effects.

The objective of this study was to determine the effects of compound small peptides of Chinese medicine (CSPCM) on the intestinal microbiota of broilers. A total of thirty-six 1-day-old Arbor Acres broilers were assigned to 6 dietary treatments that include 250, 500, and 750 g/T of CSPCM in feed, 100 g/T of Bacillus subtilis and Clostridium butyricum in feed, and 100 g/T of 50,000 IU xylanase in feed. Each treatment had 2 replicates with 2 cages (3 birds per cage). The jejunal digesta samples were collected from chickens at 42 d. Operational taxonomic unit analysis showed that adding CSPCM at a concentration of 750 g/T of feed can increase the number of operational taxonomic unit samples than other groups. Compared with the control group, adding 250 g/T of CSPCM of feed can improve content of Lactobacillus, Cupriavidus, Ochrobactrum, Candidatus&#95;Arthromitus, Acinetobacter, and Sphingomonas. Adding 500 g/T of CSPCM in feed resulted in varying degrees of improvement in Candidatus&#95;Arthromitus, Acinetobacter, and Sphingomonas. Adding 750 g/T of CSPCM in feed can increase the content of Lactobacillus and Candidatus&#95;Arthromitus. In PICRUSt function prediction analysis, CSPCM acts on the body by creating an environment suitable for the growth of beneficial bacteria. Adding 250 g/T of CSPCM in feed can improve amino acid metabolism, endocrine system function, membrane transport, and cell mobility function. Adding 500 g/T of CSPCM in feed can improve replication and repair and membrane transport function. Adding 750 g/T of CSPCM in feed can increase carbohydrate metabolism, replication and repair, and membrane transport function. Adding B. subtilis and C. butyricum in feed increased replication and repair and membrane transport function. Adding xylanase in feed increased membrane transport function. In conclusion, this study demonstrated that dietary supplementation of CSPCM to broiler diets increased beneficial flora content, metabolism of carbohydrates, amino acid metabolism, the deposition of proteins, renewal of bacteria, and maintenance of vigorous vitality. Among the 3 additive quantities of 250 g/t, 500 g/t, and 750 g/t of CSPCM in feed, 250 g/t of CSPCM improved parameters that are necessary for improved growth and production., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Keshan disease is an endemic cardiomyopathy of undefined causes. Being involved in the unclear pathogenesis of Keshan disease, a clear diagnosis, and effective treatment cannot be initiated. However, the rapid development of gut flora in cardiovascular disease combined with omics and big data platforms may promote the discovery of new diagnostic markers and provide new therapeutic options. This study aims to identify biomarkers for the early diagnosis and further explore new therapeutic targets for Keshan disease., Methods: This cohort study consists of two parts. Though the first part includes 300 participants, however, recruiting will be continued for the eligible participants. After rigorous screening, the blood samples, stools, electrocardiograms, and ultrasonic cardiogram data would be collected from participants to elucidate the relationship between gut flora and host. The second part includes a prospective follow-up study for every 6 months within 2 years. Finally, deep mining of big data and rapid machine learning will be employed to analyze the baseline data, experimental data, and clinical data to seek out the new biomarkers to predict the pathogenesis of Keshan disease., Discussion: Our study will clarify the distribution of gut flora in patients with Keshan disease and the abundance and population changes of gut flora in different stages of the disease. Through the big data platform analyze the relationship between environmental factors, clinical factors, and gut flora, the main factors affecting the occurrence of Keshan disease were identified, and the changed molecular pathways of gut flora were predicted. Finally, the specific gut flora and molecular pathways affecting Keshan disease were identified by metagenomics combined with metabonomic analysis., Trial Registration: ChiCTR1900026639. Registered on 16 October 2019.

The objective of this study was to examine the effects of chronic cyclic heat stress (HS) on the intestinal morphology, oxidative stress and cecal bacterial communities of broilers. One-day-old Arbor Acres (AA) male broilers (n = 100) were acclimated for 3 weeks and then randomly allocated into two groups, normal control (NC) group (22 ± 1 °C, 24 h/day) and HS group (32 ± 1 °C, 10 h/day lasted for 2 weeks). At 35 d of age, intestinal segments (duodenum, jejunum and ileum) and cecal digesta were collected for detection. HS affected intestinal morphology, inducing epithelial cell abscission, inflammatory cell infiltration, and lamina propria edema. Compared with the NC group, HS significantly decreased (P < 0.01) villus height (VH) and the VH-to-crypt depth (CD) ratio (VCR), increased (P < 0.05) CD in the duodenum and ileum, but had no effect on the VH in the jejunum. Moreover, HS induced oxidative stress with antioxidant enzymes activity decreasing (P < 0.05) while malondialdehyde (MDA) content increasing (P < 0.05) in small intestine. Pearson's correlation analysis indicated that MDA content was negatively correlated with VH (P < 0.05). The result of 16S rRNA sequencing showed that HS exposure impacted cecal microbiota alpha diversity (phylogenetic diversity whole-tree index) and beta diversity. Based on principal coordinate analysis (PCoA) plots for weighted UniFrac metrics and unweighted pair group method with arithmetic mean (UPGMA), there were 8 discriminative features at the genus level (linear discriminant analysis score > 2). Parabacteroides, Saccharimonas, Romboutsia and Weissella were reduced, while Anaerofustis, Pseudonocardia, Rikenella and Tyzzerella were enriched in heat-stressed broilers. Collectively, these results indicated that chronic cyclic HS induced oxidative stress that caused damage to intestinal villus-crypt structures, and then altered the cecal microflora profile., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2020. Published by Elsevier Ltd.)

Brown macroalgae are an important source of polyphenols with multiple health functions. In this work, polyphenol extracts from Lessonia trabeculate were purified and investigated for the antidiabetic activity in vitro and in vivo. The purified polyphenol extracts exhibited good antioxidant activities, α-glucosidase and lipase inhibition activities (IC 50 < 0.25 mg/mL). The HPLC-DAD-ESI-MS/MS analysis indicated that the compounds in polyphenol extracts were mainly phlorotannin derivatives, phenolic acid derivatives, and gallocatechin derivatives. In vivo, C57BL/6J rats treated with polyphenol extracts for 4 weeks had lower fasting blood glucose levels, insulin levels, as well as better serum lipid profiles and antioxidant stress parameters, compared with the diabetic control (DC) group. Histopathology revealed that polyphenol extracts preserved the architecture and function of the liver. Short-chain fatty acid contents in rats' fecal samples with polyphenols administration were significantly recovered as compared with the DC group. Furthermore, the gut microflora of rats was investigated with high-throughput 16S rRNA gene sequencing and results indicated that polyphenol extracts had a positive effect on regulating the dysbiosis of the microbial ecology in diabetic rats. All of the results from the study provided a scientific reference of the potentially beneficial effects of L. trabeculate polyphenols on diabetes management.

Ethnopharmacological Relevance: In Chinese folk medicine, the flower of Edgeworthia gardneri (Wall.) Meisn. is used to treat various metabolic diseases, such as hyperglycemia, hypertension, and hyperlipidemia., Aim of the Study: This study aimed to explore the antidiabetes potential of the flower of E. gardneri and investigate whether it can benefit the entire gut bacteria community., Materials and Methods: Chemical constituents of the extract were analyzed by UHPLC-Q Exactive Mass Spectrometer (UHPLC-QE-MS). The antidiabetes effect of the water extract (WAE) of the flower of E. gardneri was evaluated in diabetic mice induced by high-fat diet (HFD) and streptozotocin (STZ) (six groups, n = 8) daily at doses of 1, 2, and 3 g/kg for 4 weeks. The gut microbiota was analyzed using high-throughput 16S rRNA gene sequencing. Short-chain fatty acids (SCFAs) in the fecal were also investigated., Results: UHPLC-QE-MS analysis identified 29 compounds, including five alkaloids, six coumarins, four flavonoids, 11 organic acids, and three additional compounds, in the WAE. Results showed that the high dose of WAE considerably decreased the blood glucose level by 30.0%. Furthermore, E. gardneri significantly ameliorated insulin resistance and lipid metabolism dysfunction and repaired islet, hepatic, and white fat and colon histology in diabetic mice. Diabetic mice treated with WAE showed apparent changes in the structure and composition of the gut microbiota. WAE reversed the changes in Clostridiales, Lachnospiraceae, S24-7, Rikenellaceae, and Dorea in diabetic mice. The correlation analysis indicated that key OTUs were related to diabetes indices. The amounts of SCFAs, including acetic, propionic, and valeric acids, were significantly high in WAE-treated diabetic groups., Conclusions: E. gardneri treatment improved the glucose metabolism and reshaped the unbalanced gut microbiota of diabetic mice. Our study provides evidence for application of E. gardneri to treatment of diabetes mellitus., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Dexamethasone (Dex), an artificially synthetic cortisol substitute, is commonly used as an anti-inflammatory drug, and is also employed to mimic the stress state experimentally. It is well known that chronic stress disturbs the gut microbiota community and digestive functions. However, no relevant studies have been conducted in ruminants., Results: In this study, a low dosage of Dex (0.2 mg/kg body weight, Dex group, n = 5) was consecutively injected intramuscularly for 21 days to simulate chronic stress in growing goats. Goats were injected with saline (0.2 mg/kg body weight) as the control group (Con, n = 5). Dex-treated goats showed a higher number of white blood cells and blood glucose levels (p < 0.01), but lower dry matter intake (DMI) and body weight (p < 0.01) than those of saline-injected goats. Plasma cortisol concentration decreased significantly in response to the Dex injection compared to the control (p < 0.05). The Dex treatment did not change most ruminal volatile fatty acid (VFAs) concentrations before the morning feeding after 1-21 days of treatment (p > 0.05); however, ruminal VFA concentrations decreased dramatically 2, 4, 6, and 8 h after the morning feeding on day 21 of the Dex injections. In this study, chronic Dex exposure did not alter the community structure of microbes or methanogenes in the rumen, caecum, or colonic digesta. Only Prevotella increased on days 7 and 14 of Dex treatment, but decreased on day 21, and Methanosphaera was the only genus of methanogene that decreased., Conclusions: Our results suggest that chronic Dex exposure retards growth by decreasing DMI, which may be mediated by higher levels of blood glucose and lower ruminal VFA production. Microbiota in the digestive tract was highly resistant to chronic Dex exposure.

Inflammatory bowel disease (IBD) is a disease caused by a dysregulated immune with unknown etiology. Hericium erinaceus (H. erinaceus) is a Chinese medicinal fungus, with the effect of prevention and treatment of gastrointestinal disorders. In this study, we have tested the anti-inflammatory effect of polysaccharide of H. erinaceus (HECP, Mw: 86.67 kDa) in the model of dextran sulfate sodium (DSS)-induced colitis in C57BL/6 mice. Our data indicated that HECP could improve clinical symptoms and down-regulate key markers of oxidative stresses, including nitric oxide (NO), malondialdehyde (MDA), total superoxide dismutase (T-SOD), and myeloperoxidase (MPO). HECP also suppressed the secretion of interleukin (IL)-6, interleukin (IL)-1β, tumor necrosis factor (TNF)-α and the expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and decreased the expression of related mRNA. Meanwhile, HECP blocked phosphorylation of nuclear factor-κB (NF-κB) p65, NF-κB inhibitor alpha (IκB-α), mitogen-activated protein kinases (MAPK) and Protein kinase B (Akt) in DSS-treated mice. Moreover, HECP reversed DSS-induced gut dysbiosis and maintained intestinal barrier integrity. In conclusion, HECP ameliorates DSS-induced intestinal injury in mice, which suggests that HECP can serve as a protective dietary nutrient against IBD., (Copyright © 2018. Published by Elsevier Inc.)

Gut-derived bacterial lipopolysaccharide (LPS) and subsequent hepatic toll-like receptor 4 (TLR4) activation have been recognized to be involved in the onset of diet-induced nonalcoholic fatty liver disease (NAFLD), but little is known about the variation of LPS and TLR4 during the progression of NAFLD. Probiotics were able to inhibit proliferation of harmful bacteria and improve gastrointestinal barrier function. However, it's unclear whether LPS/TLR4 is involved in the protection effect of probiotics on NAFLD. In this study, we described characteristic of gut microbiota structure in the progression of NAFLD, and we also analyzed the relationship between gut microbiota and LPS/TLR4 in this process. Furthermore, we applied probiotics intervention to investigate the effect of probiotics on gut flora structure, intestinal integrity, serum LPS, liver TLR4 and liver pathology. Our results showed that serum LPS and liver TLR4 were highly increased during progression of NAFLD, with gut flora diversity and gut mircobiological colonization resistance (B/E) declining. Furthermore, probiotics could improve gut microbiota structure and liver pathology. Probiotics could also downregulate serum LPS and liver TLR4. Our results suggested that both gut flora alteration and endotoxemia may be involved in the progression of NAFLD. Probiotics may delay the progression of NAFLD via LPS/TLR4 signaling.