Gut Microbiota Imbalance Research Articles

Gut microbiota microbial metabolites in diabetic nephropathy patients: far to go.

Diabetic nephropathy (DN) is one of the main complications of diabetes and a major cause of end-stage renal disease, which has a severe impact on the quality of life of patients. Strict control of blood sugar and blood pressure, including the use of renin-angiotensin-aldosterone system inhibitors, can delay the progression of diabetic nephropathy but cannot prevent it from eventually developing into end-stage renal disease. In recent years, many studies have shown a close relationship between gut microbiota imbalance and the occurrence and development of DN. This review discusses the latest research findings on the correlation between gut microbiota and microbial metabolites in DN, including the manifestations of the gut microbiota and microbial metabolites in DN patients, the application of the gut microbiota and microbial metabolites in the diagnosis of DN, their role in disease progression, and so on, to elucidate the role of the gut microbiota and microbial metabolites in the occurrence and prevention of DN and provide a theoretical basis and methods for clinical diagnosis and treatment.

Friend or Foe: Exploring the Relationship between the Gut Microbiota and the Pathogenesis and Treatment of Digestive Cancers.

Digestive cancers are among the leading causes of cancer death in the world. However, the mechanisms of cancer development and progression are not fully understood. Accumulating evidence in recent years pointing to the bidirectional interactions between gut dysbiosis and the development of a specific type of gastrointestinal cancer is shedding light on the importance of this "unseen organ"-the microbiota. This review focuses on the local role of the gut microbiota imbalance in different digestive tract organs and annexes related to the carcinogenic mechanisms. Microbiota modulation, either by probiotic administration or by dietary changes, plays an important role in the future therapies of various digestive cancers.

Fucoidan from Apostichopus japonicus ameliorates alcoholic liver disease by regulating gut-liver axis homeostasis

Long-term and excessive alcohol consumption can lead to the development of alcoholic liver disease (ALD), characterized by oxidative damage, intestinal barrier injury, and disruption of intestinal microbiota. In this study, we extracted fucoidan (Aj-FUC) from Apostichopus japonicus using enzymatic methods and characterized its structure. The ALD model was established in male Balb/c mice using 56° Baijiu, with silymarin as a positive control. Mice were orally administered 100 mg/kg·bw and 300 mg/kg·bw of Aj-FUC for 28 days to evaluate its effects on liver injury in ALD mice and explore its potential role in modulating the gut-liver axis. The results showed significant improvements in histopathological changes and liver disease in the Aj-FUC group. Aj-FUC treatment significantly increased the levels of glutathione (GSH) and glutathione peroxidase (GSH-Px) while weakly reduced the elevation of malondialdehyde (MDA) induced by ALD. It also regulated the Nrf2/HO-1 signaling pathway, collectively alleviating hepatic oxidative stress. Aj-FUC intervention upregulated the expression of ZO-1 and Occludin, thus contributing to repair the intestinal barrier. Additionally, Aj-FUC increased the content of short-chain fatty acids (SCFAs) and regulated the imbalance in gut microbiota. These results suggested that Aj-FUC alleviates ALD by modulating the gut-liver axis homeostasis. It may prove to be a useful dietary supplement in the treatment of alcoholic liver damage.

Oral Synergism of Egg-White-Derived Peptides (EWDP) and Curcumin for Colitis Mitigation via Polysaccharide/Cyclodextrin Metal-Organic Framework-Based Assemblies.

Recently, oral deliverable strategies of multiple nutraceuticals for ulcerative colitis (UC) mitigation have attracted increasing attention. This study aimed to fabricate facile oral assemblies loaded with egg-white-derived peptides (EWDP) and curcumin based on carboxymethyl chitosan (CMCS) and an γ-cyclodextrin metal-organic framework (MOF). Herein, outer CMCS could coassemble with EWDP (both nutraceuticals and building blocks) into cobweb-like fibrils to promote bridging with inner MOF via coordinative noncovalent interactions (hydrogen bonding, hydrophobic interaction, and electrostatic interaction). Compared with conventional γ-cyclodextrin/MOF-based composites, the above coassembly could also endow the biocompatible assemblies with superior nanoscale colloidal properties, processing applicability (curcumin storage stability, bioaccessibility, and aqueous solubility), and bioactivity. Moreover, the oral synergism of EWDP and curcumin (initially nonsynergistic) for UC mitigation was achieved by alleviating inflammatory damage and gut microbiota imbalance. Overall, the novel assemblies could be a promising amplifier and platform to facilitate oral formulations of various nutraceuticals for food processing and UC relief.

Vitamin C alleviates rheumatoid arthritis by modulating gut microbiota balance.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic and symmetric in-flammation. Our previous research revealed an imbalance in the gut flora of RA patients and showed that certain gut microbiota can accelerate RA progression by enhancing vitamin C degradation. However, it is unclear whether vitamin C supplementation could improve the gut microbiota to prevent the development of arthritis by interfering with the gut-joint axis. In this work, we aimed to evaluate the effects of vitamin C in regulating the gut microbiota and to elucidate its potential role in the onset and progression of RA in a mouse model, thus providing a basis for the development of new intervention strategies and treatments for RA. In this study, collagen-induced arthritis (CIA) mouse models, biochemical, histological and 16S rRNA microbiological methods were used to investigate the role and possible mechanism of vitamin C in rheumatoid arthritis. The results showed that treatment of CIA mice with vitamin C effectively rescued the gut mi-crobiota imbalance and suppressed the inflammatory response associated with RA, and effectively alleviated arthritis symptoms in mice in which levels of the pro-inflammatory cytokines IL-6 and TNF-α were specifi-cally reduced. In conclusion, our results demonstrate the potential of vitamin C as a potential therapeutic choice for RA.

The gut microbiota-constipation connection: Insights from a two sample bidirectional Mendelian randomization study

ObjectiveThe dysbiosis of the gut microbiota has been implicated in various maladies. Research has identified an association between the dysbiosis of the gut microbiota and the risk of constipation, prompting this study to elucidate the potential causal relationship between gut microbiota imbalance with constipation through a two sample bidirectional Mendelian randomization (MR) study, shedding light on the genetic mechanisms underlying the connection between gut microbiota and constipation. MethodsThe forward MR analysis aimed to scrutinize whether alterations in the composition and abundance of gut microbiota impact the risk of constipation, while the reverse MR analysis explored whether the genetic predisposition to constipation influences the abundance of gut microbiota. Genomic correlation data for the gut microbiota were sourced from the comprehensive statistics of the MiBioGen consortium. Genomic correlation data for constipation were obtained from the IEU database, encoded as the dataset ebi-a-GCST90018829. The correlation was assessed using various analytical techniques, including inverse variance weighting (IVW), Mendelian randomization-Egger regression (MR-Egger), and weighted median and mode methodologies. To ensure the robustness of the results, a meticulous sensitivity analysis was conducted, incorporating Cochran's Q test, MR-Egger intercept test, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and a Leave-one-out analysis. ResultsIn the forward Mendelian randomization analyses, a negative correlation was discerned between the abundance of Coprococcus in the gut microbiota and the occurrence of constipation (IVW: OR = 0.74, 95 % CI = 0.64–0.86, p = 0.0001), whereas a positive correlation was observed between the abundance of Bacteroidetes in the gut microbiota and constipation (IVW: OR = 1.22, 95 % CI = 1.00–1.50, p = 0.04). In the forward Mendelian randomization analyses, we were unsuccessful in obtaining valid instrumental variables for scrutiny, and we deemed that constipation exerts no influence on the composition of the gut microbiota. ConclusionGenetic predisposition towards increased abundance of Coprococcus and decreased abundance of Bacteroidetes is correlated with a diminished susceptibility to constipation. This investigation showed that alterations in the gut microbiota precipitated the onset of constipation, rather than constipation inducing modifications in the microbial flora.

S/O/W Emulsion with CAPE Ameliorates DSS-Induced Colitis by Regulating NF-κB Pathway, Gut Microbiota and Fecal Metabolome in C57BL/6 Mice.

Inflammatory bowel disease (IBD) has attracted much attention worldwide due to its prevalence. In this study, the effect of a solid-in-oil-in-water (S/O/W) emulsion with Caffeic acid phenethyl ester (CAPE, a polyphenolic active ingredient in propolis) on dextran sulfate sodium (DSS)-induced colitis in C57BL/6 mice was evaluated. The results showed that CAPE-emulsion could significantly alleviate DSS-induced colitis through its effects on colon length, reduction in the disease activity index (DAI), and colon histopathology. The results of ELISA and Western blot analysis showed that CAPE-emulsion can down-regulate the excessive inflammatory cytokines in colon tissue and inhibit the expression of p65 in the NF-κB pathway. Furthermore, CAPE-emulsion promoted short-chain fatty acids production in DSS-induced colitis mice. High-throughput sequencing results revealed that CAPE-emulsion regulates the imbalance of gut microbiota by enhancing diversity, restoring the abundance of beneficial bacteria (such as Odoribacter), and suppressing the abundance of harmful bacteria (such as Afipia, Sphingomonas). The results of fecal metabolome showed that CAPE-emulsion restored the DSS-induced metabolic disorder by affecting metabolic pathways related to inflammation and cholesterol metabolism. These research results provide a scientific basis for the use of CPAE-emulsions for the development of functional foods for treating IBD.

Exploring the Role of Gut Microbiota in Patients with Alopecia Areata.

Imbalances in gut microbiota reportedly contribute to the development of autoimmune diseases, but the association between the etiopathogenesis of alopecia areata (AA) and gut microbial dysbiosis remains unclear. This cross-sectional study was conducted to identify and compare the composition of the gut microbiome in patients affected by AA and those in a healthy control (HC) group, and to investigate possible bacterial biomarkers for the disease. Fecal samples were collected from 19 AA patients and 20 HCs to analyze the relationship with fecal bacteria. The three major genera constituting the gut microbiome of AA patients were Bacteroides, Blautia, and Faecalibacterium. The alpha diversity of the AA group was not statistically significant different from that of the HC group. However, bacterial community composition in the AA group was significantly different from that of HC group according to Jensen-Shannon dissimilarities. In patients with AA, we found an enriched presence of the genera Blautia and Eubacterium_g5 compared to the HC group (p < 0.05), whereas Bacteroides were less prevalent (p < 0.05). The gut microbiota of AA patients was distinct from those of the HC group. Our findings suggest a possible involvement of gut microbiota in in the as-yet-undefined pathogenesis of AA.

Effects of xylo-oligosaccharide on gut microbiota, brain protein expression, and lipid profile induced by high-fat diet

Midlife overweight and obesity are risk factors of cognitive decline and Alzheimer' s disease (AD) in late life. In addition to increasing risk of obesity and cognitive dysfunction, diets rich in fats also contributes to an imbalance of gut microbiota. Xylo-oligosaccharides (XOS) are a kind of prebiotic with several biological advantages, and can selectively promote the growth of beneficial microorganisms in the gut. To explore whether XOS can alleviate cognitive decline induced by high-fat diet (HFD) through improving gut microbiota composition, mice were fed with normal control or 60% HFD for 9 weeks to induce obesity. After that, mice were supplemented with XOS (30 g or 60 g/kg-diet) or without, respectively, for 12 weeks. The results showed that XOS inhibited weight gain, decreased epidydimal fat weight, and improved fasting blood sugar and blood lipids in mice. Additionally, XOS elevated spatial learning and memory function, decreased amyloid plaques accumulation, increased brain-derived neurotrophic factor levels, and improved neuroinflammation status in hippocampus. Changes in glycerolipids metabolism-associated lipid compounds caused by HFD in hippocampus were reversed after XOS intervention. On the other hand, after XOS intervention, increase in immune-mediated bacteria, Faecalibacterium was observed. In conclusion, XOS improved gut dysbiosis and ameliorated spatial learning and memory dysfunction caused by HFD by decreasing cognitive decline-associated biomarkers and changing lipid composition in hippocampus.

Overview of cloning in lactic acid bacteria: Expression and its application of probiotic potential in inflammatory bowel diseases.

Inflammatory bowel disease (IBD) imposes a significant impact on the quality of life for affected individuals. However, there was a current lack of a systematic summary regarding the latest epidemic trends and the underlying pathogenesis of IBD. This highlights the need for a thorough examination of both the epidemiological aspects of IBD and the specific mechanisms by which lactic acid bacteria (LAB) contribute to mitigating this condition. In developed countries, higher incidences and death rates of IBD have been observed, influenced by a combination of environmental and genetic factors. LAB offer significant advantages and substantial potential for enhancing IBD treatment. LAB's capabilities include the production of bioactive metabolites, regulation of gut immunity, protection of intestinal mechanical barriers, inhibition of oxidative damage, and restoration of imbalanced gut microbiota. The review suggests that screening effective LAB using cell models and metabolites, optimizing LAB intake through dose-effect studies, enhancing utilization through nanoencapsulation and microencapsulation, investigating mechanisms to deepen the understanding of LAB, and refining clinical study designs. These efforts aim to contribute to comprehending the epidemic trend, pathogenesis, and treatment of IBD, ultimately fostering the development of targeted therapeutic products, such as LAB-based interventions.

Research progress of traditional Chinese medicine intervention for ulcerative colitis based on Notch1 signaling pathway

Ulcerative colitis(UC) is one of the common gastrointestinal diseases worldwide. In recent years, the incidence of UC has been continuously increasing, seriously threatening the health of people globally. It thus has become an urgent problem that needs to be addressed. There is research evidence that intestinal mucosal barrier dysfunction, including changes in intestinal stem cell secretion lineage, mucosal layer damage, disruption of cell junctions, overactive immune function, and imbalanced gut microbiota, is an important pathogenic factor and molecular basis of UC. The Notch signaling pathway is a highly conserved signaling pathway in eukaryotes during evolution, which transmits signals through cell connections between adjacent cells, affecting a series of processes such as cell proliferation, differentiation, development, migration, and apoptosis. Therefore, the Notch signaling pathway can regulate intestinal stem cells, CD4~+T cells, innate lymphoid cells(ILCs), macrophages(MØ), and intestinal microbiota and thus affect the chemical, physical, immune, and biological mucosal barriers of the intestinal mucosa. Its function is extensive and unique, different from those signaling pathways that mainly focus on anti-inflammatory and antioxidant stress. It can explain the therapeutic effects of traditional Chinese medicine from different perspectives. This article reviewed the role of the Notch1 signaling pathway in the pathogenesis of UC and the relevant literature on the targeted prevention and treatment of UC with traditional Chinese medicine, so as to provide new targets and theoretical support for further research on the effective prevention and treatment of UC.

Therapeutic effect and mechanism of Jingfang Granules on acute lung injury based on intestinal flora and fecal metabolomics

This study aims to elucidate the therapeutic effect and mechanism of Jingfang Granules on acute lung injury, and to investigate the regulatory effect of Jingfang Granules on the metabolic disorders of endogenous metabolites in feces and the homeostasis of intestinal microbiota in acute lung injury, mice were randomly divided into a sham group, a model group, and a Jingfang Granules group. After modeling, the mice were continuously administered for 6 days. Using ultra-high performance liquid chromatography quadrupole/electrostatic field orbital trap high-resolution mass spectrometry(UHPLC-HESI-QE-Orbitrap-MS/MS) metabolomics technology and 16S rRNA high-throughput sequencing technology, changes in endogenous small molecule substances and gut microbiota in mouse intestines were determined, and potential biomarkers were identified. The results showed that Jingfang Granules can regulate 11 biomarkers, including L-glutamic acid, succinic acid, arachidonic acid, linoleic acid, linolenic acid, phenylalanine, sphingosine, 2-hydroxy-2-methyl butyric acid, pyruvate, tryptophan, and palmitic acid. Metabolic pathway analysis was conducted on these 11 biomarkers using the online software MetaboAnalyst, identifying potential major metabolic pathways. Among them, a total of 10 metabolic pathways are closely related to the treatment of acute lung injury with Jingfang Granules, including alanine, aspartate and glutamate metabolism, aminoacyl-tRNA biosynthesis, citrate cycle(TCA cycle), alyoxylate and dicarboxylate metabolism, arginine and proline metabolism, linoleic acid metabolism and linolenic acid metabolism, nitrogen metabolism, D-glutamine and D-gluta-matemetabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism. The results of gut microbiota showed significant differences in bacteria, mainly including Bacteroides, Akkermansia, Lachnospiraceae＿NK4A136＿group, Lachnochlostridium, and Klebsiella. Spearman analysis confirms that Akkermansia and Lachnospiraceae＿NK4A136＿group is a significant positive correlation between the abundance of succinic acid, arachidonic acid, linolenic acid, linoleic acid, butyric acid, and pyruvate in the group; Bacteroides, Klebsiella, Lachnochlostrium are significantly positively correlated with the abundance of L-glutamic acid, phenylalanine, and sphingosine. The above results indicate that the therapeutic effect of Jingfang Granules on acute lung injury is achieved by improving the imbalance of gut microbiota in mice with acute lung injury, balancing the metabolism of alanine, biosynthesis of aminoacyl tRNA, aspartic acid, glutamate, tricarboxylic acid cycle, biosynthesis of phenylalanine, tyrosine, tryptophan, and metabolism of linoleic acid.

Dysbiosis in Multiple Sclerosis: Can Immunoglobulin Y Supplements Help?

The role of gut microbiota in autoimmune disorders like multiple sclerosis is gaining attention. Multiple sclerosis is characterized by inflammation, demyelination, and neurodegeneration in the central nervous system. Alterations in gut microbiota have been linked to multiple sclerosis development, with decreased beneficial bacteria and increased harmful species. The gut-brain axis is a complex interface influencing bidirectional interactions between the gut and the brain. Dysbiosis, an imbalance in gut microbiota, has been associated with autoimmune diseases. The influence of gut microbiota in multiple sclerosis is reversible, making it a potential therapeutic target. Probiotics, prebiotics, and fecal microbiota transplantation have shown promise in multiple sclerosis treatment, with positive effects on inflammation and immune regulation. Immunoglobulin Y (IgY) supplements derived from chicken egg yolk have potential as nutraceuticals or dietary supplements. IgY technology has been effective against various infections, and studies have highlighted its role in modulating gut microbiota and immune responses. Clinical trials using IgY supplements in multiple sclerosis are limited but have shown positive outcomes, including reduced symptoms, and altered immune responses. Future research directions involve understanding the mechanisms of IgY's interaction with gut microbiota, optimal dosage determination, and long-term safety assessments. Combining IgY therapy with other interventions and investigating correlations between microbiota changes and clinical outcomes are potential avenues for advancing multiple sclerosis treatment with IgY supplements.

Role of the gut microbiota and innate immunity in polycystic ovary syndrome: Current updates and future prospects.

Polycystic ovary syndrome (PCOS) is one of the modern intractable reproductive diseases. The female irregular menstruation, infertility, obesity, and so forth caused by PCOS have become a hot issue affecting family harmony and social development. The aetiology of PCOS is complex. In recent years, many scholars have found that its pathogenesis was related to the imbalance of gut microbiota. Gut microbiota can form two-way communication with the brain through the 'gut-brain axis' and affect the host's metabolism. Current research has confirmed that the gut microbiota can interfere with glucose and lipid metabolism, insulin sensitivity, hormone secretion and follicular development in women by altering intestinal mucosal permeability and secreting metabolites. In addition, the diversity and composition of gut microbiota of PCOS patients changed, which may affect the metabolic function of the gut microbiota and the ability to produce metabolites, and may also directly or indirectly affect the endocrine function. This study reviewed recent research advances about the role of gut microbiota in PCOS. In order to provide basis for prevention and treatment of PCOS based on gut microbiota.

Abstract 1480: Perfluorooctanesulfonic acid exposure promotes pathological changes in normal intestinal tissues which may lead to an increased risk of colorectal cancer development

Abstract Introduction: Long-term exposures to per- and polyfluoroalkyl substances (PFAS) have been increasingly linked to negative health outcomes including metabolic disorders, reduced immune responses, and increased risk of cancer. PFOS, one the most frequently detected PFAS in drinking water, is readily absorbed in the GI tract and distributes predominantly to the plasma and liver. Even though recent studies demonstrate that PFOS can cause an imbalance of cecal gut microbiota, alter microbiota diversity, and promote inflammation and gut barrier dysfunction, there is still not much known about the effects of PFOS exposure on normal and pre-malignant intestinal tissues and its contribution to carcinogenesis. Therefore, the goal of this study is to investigate the effects of PFOS on normal (I) and malignant intestinal cells (II). Methods: The effect of PFOS on gene expression profile was assessed by RNAseq analysis in intestinal tissue of C57BL/6 mice. Tumor organoids were established from Apc/VillinCre mice (adenoma models). Organoid cultures, colorectal cancer (CRC) and primary normal intestinal cell lines have been treated with 1μg/ml of PFOS. To access the mechanisms involved in PFOS-induced intestinal alterations, qRT-PCR, western blot, immunofluorescence, cytokine array and metabolomics analysis have been performed. Results: The RNAseq analysis showed that PFOS exposure is associated with transcriptome alterations with exacerbated changes in pathways involved in lipid metabolism, immune system regulation and pro-carcinogenesis signaling. PFOS exposure leads to a significant decrease in expression of 3-hydroxy-3-methylglutaryl-Coa synthase 2 (HMGCS2), a rate limiting ketogenic enzyme, in intestinal tissues. We also showed that PFOS exposure upregulates fatty acid synthase, a key enzyme of de novo lipogenesis, programmed death-ligand, an immune checkpoint inhibitor, and altered the levels of pro-inflammatory cytokines and metabolites. Using HMGCS2 knockout cells, we identified the possible contribution of HMGCS2 in cytokine regulation and activation of oncogenic pathways. Conclusion: In summary, our data suggests that PFOS may induce gastrointestinal pathological changes that can increase the risk of CRC development. Further studies are warranted to determine the functional significance of PFOS-mediated downregulation of HMGCS2 and upregulation of lipid metabolism in intestinal cells. Delineating the effects of PFOS on intestinal epithelium may contribute to development of interventional strategies to eliminate harmful effects of these environmental pollutants. Citation Format: Josiane Weber Tessmann, Jerika Durham, Ryan Goettl, Dang he, Chi Wang, Pan Deng, Bernhard Hennig, Yekaterina Zaytseva. Perfluorooctanesulfonic acid exposure promotes pathological changes in normal intestinal tissues which may lead to an increased risk of colorectal cancer development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1480.

Lactobacillus paracasei ZFM54 alters the metabolomic profiles of yogurt and the co-fermented yogurt improves the gut microecology of human adults

Gut microbiota imbalance could lead to various diseases, making it important to optimize the structure of the gut flora in adults. Lactobacillus paracasei ZFM54 is a bacteriocin- and folic acid-producing Lactobacillus strain. Herein, L. paracasei ZFM54 was used as the potentially probiotic bacterium to ferment milk together with a yogurt starter. We optimized the fermentation conditions, and the obtained yogurts were then subjected to volatile and nonvolatile metabolome analysis, showing that L. paracasei ZFM54 can not only improve the acidity, water holding capacity and live lactic acid bacteria counts, but also improve many volatile acid contents and increase some beneficial nonvolatile metabolites, such as N-ethyl glycine and l-lysine, endowing the yogurt with more flavor and better function. The regulatory effects of the co-fermented yogurt on the intestinal microecology of volunteers were investigated by 16S rRNA sequencing and short-chain fatty acid (SCFA) analysis after consuming the yogurt for a 2-wk period, showing a better effect to increase the relative abundance of beneficial bacteria such as Ruminococcus and Alistipes, decrease harmful bacteria (Escherichia-Shigella and Enterobacter), and enhance the production of SCFA (acetate, propionate, and butyric acid) compared with the control yogurt. We found that L. paracasei ZFM54 can significantly improve the health benefits of yogurt, laying the foundation for its commercial application in improving gut microbiota.

Isoleucine‐restricted diets improve high‐fat diet‐induced nonalcoholic fatty liver disease via regulating insulin resistance and gut microbiota

AbstractObesity, caused by a long‐term high‐fat diet, is a risk factor for insulin resistance and nonalcoholic fatty liver disease (NAFLD). The gut microbiota plays an important role in NAFLD development by producing lipopolysaccharides (LPS). Isoleucine (ILE), as one of the branched‐chain amino acids (BCAAs), has a negative effect on glucose and lipid metabolism in obese mice. Therefore, we speculated that isoleucine‐restricted diets could prevent high‐fat diet‐induced insulin resistance and NAFLD. For this purpose, 30 C57BL/6J mice received a control check diet (CK), a high‐fat diet (HFD), and a isoleucine‐restricted diet (IR) for 12 weeks, respectively. The current study revealed that IR diets reversed HFD‐induced weight gain, increased fasting glucose levels, and lipid metabolism disorder. Furthermore, IR diets attenuated HFD‐induced hepatic inflammation by regulating the LPS/TLR4/NF‐κB signaling pathway. Moreover, hepatic insulin resistance and gluconeogenesis disorder were significantly improved by IR diets. In addition, IR diets reshaped HFD‐induced gut microbiota imbalance, reflected in decreasing the proportion of Proteobacteria phylum and LPS contents. Taken together, our studies support that restricting isoleucine in high‐fat diets was a novel means of preventing obesity‐induced NAFLD and insulin resistance.

140 High-resolution characterization of the gut microbiota of neonatal dairy calves using full-length 16S rRNA gene amplicon sequencing

Abstract The gut microbiota has a crucial role in preventing pathogen colonization and training the immune system. An imbalanced gut microbiota tends to induce calf diarrhea, which can lead to dehydration and metabolic acidosis. Therefore, it is urgent to identify critical factors that influence the establishment of gut microbiota in the early stages of development in dairy calves. Most previous research relied on short-read-based partial 16S rRNA gene amplicon sequencing to study calf microbiota, which has limited taxonomic resolution. The aim of our study is to obtain a species-level characterization of calf gut microbiota using long-read based full-length 16S rRNA gene amplicon sequencing and investigate the factors that affect the gut microbiota composition in the early stages of development in dairy calves. We collected fecal samples from the recto-anal junction of 25 Holstein-Angus crossed calves at d 4 and d 14 after birth. The calves were raised in individual outdoor hutches from birth and fed milk replacer twice daily. The gut microbiota was analyzed using full-length 16S rRNA gene amplicon sequencing on an Oxford Nanopore sequencer. The results revealed that the gut microbial diversity measured by Chao 1 (P &amp;lt; 0.001) and Shannon index (P &amp;lt; 0.001) significantly increased from d 4 to d 14. We identified 15 and 36 core bacterial species (prevalence ≥ 80%) in d 4 and d 14 gut microbiota, respectively, and both stages share 7 bacterial species: Bacteroides fragilis, Butyricicoccus pulicaecorum, Enterocloster bolteae, Escherichia coli, Lachnoclostridium sp YL32, Rumiococcus gnavus and Streptococcus equinus. The calf gut microbiota was dominated by Bacteroides fragilis (18%), Escherichia coli (13%), Ruminococcus gnavus (10%) and Butyricicoccus pulicaecorum (6%) species on d 4, and Megamonas rupellensis (18%) and Fusobacterium varium (6%) species (relative abundance &amp;gt; 5%) on d 14. Notably, we found a significant impact of hutch location on the composition of gut microbiota, particularly on d 4, but the impact was reduced on d 14. Moreover, there were 4 dystocia calves among the 25 calves, which had a significantly lower Shannon index (P = 0.046) compared with 4 paired normal calves of similar age and sex, and location balanced. In conclusion, this study provides a species-level resolution of gut microbiota for neonatal dairy calves and indicates a potential impact of dystocia on early microbiota development. Additionally, calf microbiota composition is influenced by environmental factors, likely the soil microbiota where hutches were located, with a more substantial effect on the microbiota at an earlier age.

Construction of nanoparticles from blueberry anthocyanins-lecithin/gum Arabic improves lipid droplet accumulation and gut microbiota disturbance in HFD-induced obese mice

The digestive instability of anthocyanins (ACNs) limits their application in food nutrition, especially precision nutrition. Blueberry ACNs-loaded nanoparticles (Lipo/GA-ACNs NPs) were prepared using gum arabic (GA) as the delivery carrier and liposomal vesicles (Lipo) prepared from soy lecithin as the targeting scaffold. The average particle size of the NPs was 99.4 nm, and the polydispersion index (PDI) was 0.46. The results showed that the presence of the Lipo-GA matrix enhanced the NPs' in vitro stability and antioxidant activity. In addition, the in vitro biocompatibility, uptake ability, lipid-lowering activity, and free-radical scavenging ability were improved to a certain extent. In a high-fat diet (HFD)-induced obese mouse model, oral administration of ACNs-LNP (LNP, liver-targeted nanoparticle) showed better effects on body weight, liver injury, and lipid droplet accumulation in the liver than ACNs. In addition, ACNs-LNP also played a role in regulating HFD-induced gut microbiota imbalance. These results provide a promising ACNs delivery strategy with the potential to be developed into a functional food that targets the liver to prevent fatty liver.

Dynamic changes in the gut microbiota after bismuth quadruple therapy and high-dose dual therapy for Helicobacter pylori eradication.

A novel regimen with high-dose dual therapy (HDDT) has emerged, but its impact on the gut microbiota is not well understood. This study aimed to evaluate the impact of HDDT on the gut microbiota and compareit with that of bismuth quadruple therapy (BQT). We enrolled outpatients (18-70 years) diagnosed with Helicobacter pylori infection by either histology or a positive 13C-urea breath test (13C-UBT) and randomly assigned to either the BQT or HDDT group. Subjects consented to provide fecal samples which were collected at baseline, Week 2, and Week 14. Amplification of the V1 and V9 regions of the 16S rRNA was conducted followed by high-throughput sequencing. Ultimately, 78 patients (41 patients in the HDDT group and 37 in the BQT group) were enrolled in this study. Eradication therapy significantly altered the diversity of the gut microbiota. However, the alpha diversity rebounded only in the HDDT group at 12 weeks post-eradication. Immediately following eradication, the predominance of Proteobacteria, replacing commensal Firmicutes and Bacteroidetes, did not recover after 12 weeks. Species-level analysis showed that the relative abundances of Klebsiella pneumoniae and Escherichia fergusonii significantly increased in both groups at Week 2. Enterococcus faecium and Enterococcus faecalis significantly increased in the BQT group, with no significant difference observed in the HDDT group. After 12 weeks of treatment, the relative abundance of more species in the HDDT group returned to baseline levels. Eradication of H. pylori can lead to an imbalance in gut microbiota. Compared to BQT, the HDDT is a regimen with milder impact on gut microbiota.