Intestinal Flora Research Articles

Melatonin Ameliorates Cadmium‐Induced Liver Fibrosis Via Modulating Gut Microbiota and Bile Acid Metabolism

ABSTRACTCadmium (Cd) is a widespread environmental contaminant with high toxicity to human health. Melatonin has been shown to improve Cd‐induced liver damage. However, its mechanism has not yet been elucidated. In this study, we aimed to investigate the effects of melatonin on Cd‐induced liver damage and fibrosis. A combination of 16S rRNA gene sequencing and mass spectrometry‐based metabolomics was adopted to investigate changes in the gut microbiome and its metabolites on the regulation of melatonin in Cd‐induced liver injury and fibrosis of mice. Further, nonabsorbable antibiotics, a fecal microbiota transplantation (FMT) program and intestine‐specific farnesoid X receptor (FXR) knockout mice were employed to explore the mechanism of melatonin (MT) on liver injury and fibrosis in Cd treated mice. MT significantly improved hepatic inflammation, bile duct hyperplasia, liver damage, and liver fibrosis, with a notable decrease in liver bile acid levels in Cd‐exposed mice. MT treatment remodeled the gut microbiota, improved gut barrier function, and reduced the production of gut‐derived lipopolysaccharide (LPS). MT significantly decreased the intestinal tauro‐β‐muricholic acid levels, which are known as FXR antagonists. Notably, MT prominently activated the intestinal FXR signaling, subsequently inhibiting liver bile acid synthesis and decreasing hepatic inflammation in Cd‐exposed mice. However, MT could not ameliorate Cd‐induced liver damage and fibrosis in Abx‐treated mice. Conversely, MT still exerted a protective effect on Cd‐induced liver damage and fibrosis in FMT mice. Interestingly, MT failed to reverse liver damage and fibrosis in Cd‐exposed intestinal epithelial cell‐specific FXR gene knockout mice, indicating that intestinal FXR signaling mediated the protective effect of MT treatment. MT improves Cd‐induced liver damage and fibrosis through reshaping the intestinal flora, activating the intestinal FXR‐mediated suppression of liver bile acid synthesis and reducing LPS leakage in mice.

Discussion on the treatment of diabetic kidney disease based on the "gut-fat-kidney" axis.

Diabetic kidney disease is the main cause of end-stage renal disease, and its prevention and treatment are still a major clinical problem. The human intestine has a complex flora of hundreds of millions of microorganisms, and intestinal microorganisms, and their derivatives are closely related to renal inflammatory response, immune response, and material metabolism. Brown adipose tissue is the main part of adaptive thermogenesis. Recent studies have shown that activating brown fat by regulating intestinal flora has good curative effects in diabetic kidney disease-related diseases. As an emerging medical concept, the "gut-fat-kidney" axis has received increasing attention in diabetic kidney disease and related diseases. However, the specific mechanism involved needs further study. A new theoretical basis for the prevention and treatment of diabetic kidney disease is presented in this article, based on the "gut-fat-kidney" axis.

Effects of dietary Brassica rapa L. polysaccharide on growth performance, immune and antioxidant functions and intestinal flora of yellow-feathered quail.

This study aimed to explore the impact of Brassica rapa L. polysaccharides (BRP) on the growth, immune response, antioxidant capacity, and cecal microbiota in yellow-feathered quails. A total of 250 one-day-old yellow-feathered quails, evenly divided by sex, were randomly assigned to five groups, with each group comprising ten replicates of five quails each. The control group (CON) received a basic diet, while the antibiotic control group (CTC) was fed a basic diet supplemented with chlortetracycline (0.05g/kg). BRP was administered at concentrations of 0.25g/kg (Low dose BRP, LBRP), 0.5g/kg (Medium dose BRP, MBRP), and 1g/kg (High dose BRP, HBRP). The duration of the experiment was 42 days. The results indicated that, compared to the CON group, the final body weight of quails in the MBRP group significantly increased (P < 0.05), and there was a significant difference in body weight between the LBRP group and the CTC group (P < 0.05). At 21 days of age, the average weights of the thymus and bursa of Fabricius in the MBRP group were significantly greater than those in the CON group (P < 0.05), with no significant difference observed when compared to the CTC group (P > 0.05); at 42 days of age, the average weight of the thymus in the MBRP group was significantly greater than that in the CON group (P < 0.05), with no significant difference observed compared to the CTC group (P > 0.05). At 21 days of age, the levels of IgA and IgG in the MBRP group were significantly elevated compared to the CON group (P < 0.05), with no significant difference noted compared to the CTC group (P > 0.05). Additionally, the MBRP group showed significant increases in CAT, T-SOD, and GSH-Px levels (P < 0.05) compared to the CON group; the levels of IL-1β and TNF-α were significantly reduced (P < 0.05), and the level of IL-10 was significantly elevated (P < 0.05) compared to the CON group. Furthermore, 16S rRNA sequencing revealed that BRP supplementation increased the populations of beneficial cecal bacteria such as Lactococcus, Weissella, Parabacteroides, and norank_f_Ruminococcaceae, and decreased the population of the harmful bacterium Campylobacter, indicating that BRP modulates the microbial community structure in the cecum of yellow-feathered quails. In summary, BRP enhanced the growth performance, serum immunoglobulin levels, antioxidant functions, and improved the intestinal microbiota in yellow-feathered quails.

Role of CD38 in mediating the effect of Bacillus on acute pancreatitis: a study of mediated Mendelian randomization

BackgroundSome studies suggest a potential link between intestinal flora and acute pancreatitis (AP). However, the causal relationships between specific intestinal flora and AP, and the possible mediating role of immune cell traits, remain unclear.MethodsA genome-wide association study (GWAS) involving 5,959 participants was conducted to identify genetic instrumental variables associated with 473 intestinal flora taxa. Summary statistics for AP were obtained from the UK Biobank. Immune cell traits were also identified using large-scale GWAS summary data. We employed a two-sample bidirectional Mendelian randomization (MR) approach to investigate the causal relationships between intestinal flora, immune cell traits, and AP, with inverse variance weighting (IVW) as the primary statistical method. Sensitivity analyses, including the MR-Egger intercept test, Cochran’s Q test, MR-PRESSO test, and leave-one-out test, were conducted to assess the robustness of our findings. Additionally, we explored whether immune cell traits mediate the pathway from intestinal flora to AP.Results11 positive and 11 negative causal relationships were identified between genetic susceptibility in intestinal flora and AP. Furthermore, 19 positive and 9 negative causal relationships were observed between immune cell traits and AP. Notably, CD38 mediated the causal relationship between Bacillus C and AP.ConclusionsThis study is the first to uncover novel causal relationships between various intestinal flora and acute pancreatitis, emphasizing the mediating role of immune cell traits in the pathway from intestinal flora to AP. It also provides new evidence supporting the conditional pathogenicity of the Bacillus genus.

Gut microbial and metabolomics profiles reveal the potential mechanism of fecal microbiota transplantation in modulating the progression of colitis-associated colorectal cancer in mice.

Intestinal flora promotes the pathogenesis of colorectal cancer (CRC) through microorganisms and their metabolites. This study aimed to investigate the composition of intestinal flora in different stages of CRC progression and the effect of fecal microbiota transplantation (FMT) on CRC mice. The fecal microbiome from healthy volunteers (HC), colorectal adenoma (CRA), inflammatory bowel disease (IBD), and CRC patients were analyzed by 16s rRNA gene sequencing. In an azoxymethane (AOM)/dextran-sulfate-sodium (DSS)-induced CRC mouse, the effect of FMT from HC, CRA, CRC, and IBD patients on CRC mice was assessed by histological analysis. Expression of inflammation- EMT-associated proteins and Wnt/β-catenin pathway were assessed using qRT-PCR and western blot. The ratio of the fecal microorganisms and metabolomics alteration after FMT were also assessed. Prevotella, Faecalibacterium, Phascolarctobacterium, Veillonella, Alistipes, Fusobacterium, Oscillibacter, Blautia, and Ruminococcus abundance was different among HC, IBD, CRC, and CRA patients. HC-FMT alleviated disease progression and inflammatory response in CRC mice, inhibited splenic T help (Th)1 and Th17 cell numbers, and suppressed the EMT and Wnt/β-catenin pathways in tumor tissues of CRC mice. IBD-FMT, CRA-FMT, and CRC-FMT played deleterious roles; the CRC-FMT mice exhibited the most malignant phenotype. Compared with the non-FMT CRC mice, Muribaculaceae abundance was lower after FMT, especially lowest in the IBD-FMT group; while Lactobacillus abundance was higher after FMT and especially high in HC-FMT. Akkermansia and Ileibacterium abundance increased after FMT-HC compared to other groups. Metabolite correlation analysis revealed that Muribaculaceae abundance was significantly correlated with metabolites such as Betaine, LysoPC, and Soyasaponin III. Lactobacillus abundance was positively correlated with Taurocholic acid 3-sulfate, and Ileibacterium abundance was positively correlated with Linoleoyl ethanolamide. The different intestinal microbiota communities of HC, IBD, CRA, and CRC patients may be attributed to the different modulation effects of FMT on CRC mice. CRC-FMT promoted, while HC-FMT inhibited the progress of CRC. Increased linoleoyl ethanolamide levels and abundance of Muribaculaceae, Akkermansia, and Ileibacterium and reduced Fusobacterium might participate in inhibiting CRC initiation and development. This study demonstrated that FMT intervention could restore the intestinal microbiota and metabolomics of CRC mice, suggesting FMT as a potential strategy for CRC therapy.

Antibiotic-Augmented Chemodynamic Therapy for Treatment of Helicobacter pylori Infection in the Dynamic Stomach Environment.

Helicobacter pylori (H. pylori) is one of the main causes of peptic ulcer disease and gastric cancer. The overuse of antibiotics leads to bacterial drug resistance and disruption to the gut microbiome. Herein, a nanoparticle (TA-FeHMSN@Amox) was developed, comprising amoxicillin (Amox)-loaded iron-engineered hollow mesoporous silica as the core and a metal-polyphenol shell formed by tannic acid (TA) and Fe3+. In acidic stomach conditions, TA-FeHMSN@Amox generates bactericidal ·OH through Fenton/Fenton-like reactions of the degraded product Fe2+ and hydrogen peroxide (H2O2) at the infection site, achieving chemodynamic therapy (CDT). Moreover, released amoxicillin enhances therapeutic efficacy by impeding the self-repair of the bacterial cell wall damaged by CDT, overcoming the limitations of ineffective CDT under conditions lacking sufficient acidity and H2O2. The acidity-responsive CDT combined with reduced antibiotic usage ensures superior in vivo therapeutic efficacy and biocompatibility with intestinal flora, providing a highly potent strategy for treating H. pylori infections in the dynamic stomach environment.

Effects of adding niacinamide to diets with normal and low protein levels on the immunity, antioxidant, and intestinal microbiota in growing-finishing pigs.

This study aimed to investigate the effects of nicotinamide (NAM) applied to diets with different crude protein levels on immune function, antioxidant capacity, and intestinal flora in growing-finishing pigs. Forty barrows (37.0 ± 1.0 kg) were randomly allocated to one of four dietary treatments (n = 10 per group). The diets in the two phases consisted of a basal diet with 30 mg/kg NAM, a basal diet with 360 mg/kg NAM, a low-protein diet with 30 mg/kg NAM, and a low-protein diet with 360 mg/kg NAM. The results showed that dietary addition of 360 mg/kg NAM decreased IL-12, malondialdehyde, IgG and IgM contents in the plasma and increased total superoxide dismutase activity and total antioxidant capacity in the colonic mucosa (P < 0.05). Supplementing the diet with 360 mg/kg NAM increased mRNA expression of the nucleotide-binding oligomerization domain containing 2 and nuclear factor erythroid 2-related factor 2 and protein expression of nuclear factor kappa-B and toll-like receptor 4 in the colonic mucosa (P < 0.05). The concentrations of acetic acid and butyric acid in the colonic contents and the abundance of Actinobacteriota in the colon at the phylum level were significantly decreased by feeding low-protein diets (P < 0.05). Additionally, the addition of 360 mg/kg NAM to diets increased (P < 0.05) the Sobs, Ace, and Chao indices of colonic microorganisms in pigs. Overall, the rational use of NAM can improve inflammatory status, enhance antioxidant capacity and intestinal barrier function, and increase colonic microbial diversity in growing-finishing pigs.

Protective effects of YCHD on the autoimmune hepatitis mice model induced by Ad-CYP2D6 through modulating the Th1/Treg ratio and intestinal flora

BackgroundAutoimmune hepatitis (AIH) is a chronic liver inflammatory disease mediated by autoimmune reactions, the pathogenesis of AIH is probably related to the imbalance of intestinal flora. Yinchenhao decoction (YCHD) has been used to relieve AIH. However, the mechanisms underpinning YCHD’s hepatoprotective effects with the gut microbito have not been fully revealed.ObjectiveTo explore the potential mechanism of YCHD in treating AIH based on changes in the intestinal flora and Th1/Treg ratio in the spleen and hepatic hilar lymph nodes.MethodsThe AIH mice model induced by the adenovirus vectors that overexpress human cytochrome P450 family 2 subfamily D member 6 (Ad-CYP2D6) was established (untreated group). One week after the Ad-CYP2D6 injection, the AIH model mice were treated by administering YCHD by gavage for 14 days (YCHD-treated group). The therapeutic efficacy of YCHD on AIH was evaluated by detecting the histopathological changes of the liver, serum transaminases (ALT and AST), inflammatory factors (TNF-α,IL-17 and IFN-γ), and autoantibodies (including LKM-1 and LC-1). The ratio of Th1 to Treg within the spleen and hepatic hilar lymph nodes of the mice was detected by flow cytometry. The changes in the species and abundance of intestinal flora and intestinal flora metabolites were analyzed via 16S rRNA gene sequencing and gas chromatography-mass spectrometry (GC/MS) to reveal the protective mechanism of YCHD on liver injury.ResultYCHD decreased the transaminase activity (AST and ALT), the content of autoantibodies (LC-1 and LKM-1), and the serum TNF-α, IL-12, and IL-17 levels in AIH mice. The degree of inflammatory infiltration in the YCHD-treated group was significantly less than that in the untreated group. YCHD can effectively reverse the abundance and diversity of intestinal flora in AIH mice and affect the release of short-chain fatty acids (SCFAs), especially butyric acid. Moreover, the flow cytometry results showed that YCHD could also decline the ratio of Th1/Treg, which probably be induced by SCFAs via the G protein-coupled receptor (GPR).ConclusionYCHD may affect the release of SCFAs by regulating the intestinal microbiota, thereby affecting the differentiation of Th1 and Treg, and achieving the effect of alleviating liver damage.

Structural characterization and anti-fatigue mechanism based on the gut-muscle axis of a polysaccharide from Zingiber officinale.

This study aimed to characterize the structure of polysaccharide ZOPA extracted from Zingiber officinale and its purified form (ZOPA-1), and to investigate their anti-fatigue mechanisms based on the gut-muscle axis. The study found that the backbone of ZOPA-1 is primarily composed of →3,4)-α-Glcp-1→ and →4,6)-α-Glcp-(1→ linkages, with →4)-α-Glcp(1→ serving as its side chain. In exhaustive swimming experiments with mice, both crude ZOPA and purified ZOPA-1 demonstrated significant anti-fatigue effects, including enhanced glycogen storage, improved antioxidant capacity, reduced accumulation of metabolic waste products, and regulated energy metabolism in the gastrocnemius muscles. These effects may be mediated through the activation of the Keap1-Nrf2/ARE and AMPK/PGC-1α signaling pathways. Furthermore, ZOPA and ZOPA-1 modulated the intestinal flora of mice, increasing diversity, altering abundance, and regulating short-chain fatty acid concentrations, suggesting a potential role of the gut-muscle axis in mediating the anti-fatigue effects. This study provides valuable insights into the complex interplay between polysaccharides, the gut-muscle axis, and exercise-induced fatigue.

Supplementation with Chinese herbal preparations protect the gut-liver axis of Hu sheep, promotes gut-liver circulation, regulates intestinal flora and immunity

The gut-liver axis in ruminants can explain nutrient regulation, the gut-liver cycle, and immune function in ruminant biology through the gut microbe-gut metabolite-liver metabolite relationship. to investigate the effects of herbal feed additives on the gut-liver axis of Hu sheep. In this study, a broadly targeted UPLC-MS/MS metabolomics approach and 16s sequencing of gut microorganisms were used to detect, identify and quantify changes in ileal microorganisms, liver metabolites and ileal metabolites following the addition of Chinese herbal preparations. The addition of a 0.5% herbal feed additive increased ileal IgA, IgG and complement C3 levels. The addition of Chinese herbal preparations can increase the abundance of Firmicutes, Actinobacteriota, Bacteroidota, at the portal level of the ileum, increase the metabolism of organic matter and its derivatives, bile acids, amino acids and their metabolites, coenzymes, and vitamins in the liver and ileum, enhance nutrient absorption and waste metabolism, accelerate liver metabolism, promote gut-liver circulation, and improve ileal and liver immunity. This study provides a theoretical basis for understanding the effects of herbal feed additives on the gut-liver axis in ruminants.

Kaempferol Remodels Liver Monocyte Populations and Treats Hepatic Fibrosis in Mice by Modulating Intestinal Flora and Metabolic Reprogramming.

Changes in gut flora are associated with liver fibrosis. The interactions of host with intestinal flora are still unknown, with little research investigating such interactions with comprehensive multi-omics data. The present work analyzed and integrated large-scale multi-omics transcriptomics, microbiome, metabolome, and single-cell RNA-sequencing datasets from Kaempferol-treated and untreated control groups by advanced bioinformatics methods. This study concludes that kaempferol dose-dependently improved serum markers (like AST, ALT, TBil, Alb, and PT) and suppressed fibrosis markers (including HA, PC III, LN, α-SMA, and Collagen I), while kaempferol also increased body weight. Mechanistically, kaempferol improved the metabolic levels of intestinal flora dysbiosis and associated lipids. This was achieved by increasing the abundance of g__Robinsoniella, g__Erysipelotrichaceae_UCG-003, g__Coriobacteriaceae_UCG-002, and 5-Methylcytidine, all-trans-5,6- Epoxyretinoic acid, LPI (18:0), LPI (20:4), etc. to achieve this. Kaemferol exerts anti-inflammatory and immune-enhancing effects by down-regulating the Th17/IL-17 signaling pathway in PDGF-induced LX2 cells. In addition, kaempferol administration remarkably elevated CD4 + T and CD8 + T cellular proportions, thereby activating immune cells for protecting the body and controlling inflammatory conditions. The combined interaction of multiple data may explain how Kaempferol modulates the intestinal flora thereby remodeling the hepatocyte population and alleviating liver fibrosis.

Effects of different milk powders on the growth and intestinal flora in weaned rats: Comparison of special formula milk powder with ordinary milk powder

AbstractThe objective of this investigation was to examine the effects of distinct dosages of infant formula and diverse formula constituents on the growth and development of weaned rats. Fifty specific pathogen‐free (SPF) male Sprague–Dawley (SD) rats aged 3 weeks were divided into the basic diet group, 20% ordinary milk powder group, 20% special formula milk powder group, 30% ordinary milk powder group, and 30% special formula milk powder group randomly. After 28 days of feeding, compared with the basic diet group, the body mass and brain/body weight of rats in the 30% ordinary and special formula milk powder groups were decreased. At the Genus level, Bacteroides in the group supplemented with 20% special formula milk powder was significantly lower than that in the basic diet group, and Parabacteroides was significantly lower than that in the 20% ordinary milk powder group. Lactobacillus was significantly higher than those in the basic diet group and the 20% ordinary milk powder group, and Blautia was significantly higher than those in the basic diet group and the 20% and 30% ordinary milk powder groups, and UBA1819 was significantly higher than those in the other groups. The abundance of Parasutterella in the basic diet group was significantly higher than those in the groups supplemented with 20% ordinary milk powder, 20% special formula milk powder, and 30% ordinary milk powder. This study found that different doses and different formula components of infant milk powder could affect body mass and intestinal flora in Sprague–Dawley (SD) rats, and the addition of low‐dose (20%) special formula infant milk powder can increase the beneficial bacteria in the intestinal flora of rats and may reduce the pathogenic bacteria.

Lactiplantibacillus plantarum Y44 Complex Fermented Milk Regulates Lipid Metabolism in Mice Fed with High-Fat Diet by Modulating Gut Microbiota.

The benefits of fermented milk containing Lactiplantibacillus plantarum (L. plantarum) Y44, known for its weight loss properties, remain unclear. For this, we evaluated the effects of the complex fermented milk (Y44-CFM), obtained through the cofermentation of cow's milk and soybean milk with L. plantarum Y44 and traditional starters, on high-fat diet (HFD)-fed C57BL/6 mice. Our study found that the oral administration of Y44-CFM significantly reduced body weight gain and hepatic lipid accumulation in HFD-fed mice while also mitigating liver injury. Additionally, Y44-CFM regulated the expression of enzymes associated with lipid metabolism in the serum, as well as the corresponding or related genes in the liver, such as fatty acid synthase. Furthermore, HFD-induced systemic inflammation, oxidative stress, and intestinal barrier dysfunction were improved. The primary alterations in hepatic metabolism involved glycerophospholipids and amino acids, including the biosynthesis of valine, leucine, and isoleucine. The diversity and overall structure of the gut microbiota were also regulated, resulting in a significant decrease in the ratio of Firmicutes to Bacteroidetes (F/B) and unclassified_f_Lachnospiraceae, along with a notable increase in Oscillospiraceae. The correlation analysis indicated that Y44-CFM influenced hepatic lipid metabolism by mediating intestinal flora and its production of short-chain fatty acids, ultimately leading to weight reduction.

Intestinal microbiome changes and mechanisms of maintenance hemodialysis patients with constipation

BackgroundConstipation is a common symptom in maintenance hemodialysis patients and greatly affects the quality of survival of hemodialysis patients. Fecal microbiota transplantation and probiotics are feasible treatments for functional constipation, but there is still a gap in the research on the characteristics of gut flora in patients with maintenance hemodialysis combined with constipation. The aim of this study is to clarify the characteristics of the intestinal flora and its changes in maintenance hemodialysis patients with constipation.MethodsFecal samples were collected from 45 participants, containing 15 in the maintenance hemodialysis constipation group,15 in the maintenance hemodialysis non-constipation group and 15 in the healthy control group. These samples were analyzed using 16S rRNA gene sequencing. The feature of the intestinal microbiome of maintenance hemodialysis constipation group and the microbiome differences among the three groups were elucidated by species annotation analysis, α-diversity analysis, β-diversity analysis, species difference analysis, and predictive functional analysis.ResultsThe alpha diversity analysis indicated that maintenance hemodialysis constipation group was less diverse and homogeneous than maintenance hemodialysis non-constipation group and healthy control group. At the genus level, the top ten dominant genera in maintenance hemodialysis constipation group patients were Enterococcus, Escherichia-Shigella, Bacteroides, Streptococcus, Bifidobacterium, Ruminococcus_gnavus_group, Lachnospiraceae_unclassified, Faecalibacterium, Akkermansia and UCG-002. Compared with non-constipation group, the Enterococcus, Rhizobiales_unclassified, Filomicrobium, Eggerthella, Allobaculum, Prevotella_7, Gordonibacter, Mitochondria_unclassified, Lachnoanaerobaculum were significantly higher in constipation group (p&amp;lt;0.05). Compared with non-constipation group, the Kineothrix, Rhodopirellula, Weissella were significantly lower in constipation group (p&amp;lt;0.05). The predictive functional analysis revealed that compared with non-constipation group, constipation group was significantly enriched in pathways associated with pyruate metabolism, flavonoid biosynthesis.ConclusionsThis study describes for the first time the intestinal microbiome characteristics of maintenance hemodialysis patients with constipation. The results of this study suggest that there is a difference in the intestinal flora between maintenance hemodialysis patients with constipation and maintenance hemodialysis patients without constipation.

HUCMSCs Regulate Bile Acid Metabolism to Prevent Heart Failure–Induced Intestinal Injury by Inhibiting the Activation of the STAT3/NF‐κB/MAPK Signaling Pathway via TGR5

ABSTRACTThe protective effects of human umbilical cord mesenchymal stem cells (hUCMSCs) on heart failure (HF)‐induced intestinal injury have not been fully understood. Flow cytometry and immunofluorescence analysis revealed that hUCMSCs renewed themselves, grew, and transformed into various cell types. Meanwhile, hUCMSCs safeguarded against intestinal damage, regulated imbalances in the intestinal flora and bile acid metabolism, and enhanced the levels of hyodeoxycholic acid (HDCA) in pigs with HF. HDCA protected against HF‐induced intestinal injury in mice through Takeda G protein–coupled receptor 5 (TGR5). Protein analysis showed that HDCA exerted protective effects on the intestines via the signal transducer and activator of transcription 3 (STAT3)/nuclear factor kappa B (NF‐κB)/mitogen‐activated protein kinase (MAPK) signaling pathway. Mouse experiments revealed that HDCA bound to TGR5 to inhibit MAPK and NF‐κB signaling pathway activation, which relies on the STAT3 signaling pathway. Moreover, hUCMSCs protected against intestinal injury in the pig model of HF by suppressing the activation of the STAT3/NF‐κB/MAPK signaling pathway via TGR5.

Modification of Intestinal Flora Can Improve Host Metabolism and Alleviate the Damage Caused by Chronic Hypoxia

Prolonged exposure to hypoxic conditions can lead to reduced appetite, stunted growth, systemic inflammation, and pulmonary hypertension. Previous studies have indicated a correlation between gut dysbiosis and the development of hypoxia-related hazards. We designed an experiment to investigate the effect of microbiota on mitigating hypoxic damage. Gut microbiota from high-altitude-adapted species (Ochotona curzoniae) were transplanted into Sprague Dawley (SD) rats, which were then housed in a simulated 6000 m altitude environment for 30 days. After the experiment, we conducted analyses on average daily weight gain (ADG), feed conversion ratio (FCR), mean pulmonary artery pressure (mPAP), gut flora, and fecal metabolism. The results demonstrated that the ADG in the transplantation group (2.98 ± 0.17 g) was significantly higher than in the control groups (2.68 ± 0.19 g and 2.26 ± 0.13 g) (p &lt; 0.05). The FCR was reduced in the transplantation group (6.30 ± 0.33 g) compared to the control groups (8.20 ± 1.15 g and 8.83 ± 0.45 g) (p &lt; 0.05). The mPAP was decreased in the transplantation group (38.1 ± 1.13 mmHg) compared to the control groups (43.4 ± 1.30 mmHg and 43.5 ± 1.22 mmHg) (p &lt; 0.05). Multi-omics analysis revealed that Lachnospiraceae, Desulfovibrionaceae, and specific amino acid metabolic pathways play crucial roles in hypoxia and are associated with both inflammation and nutritional metabolism. This study proposes a novel approach to the treatment of hypoxic pulmonary hypertension and holds potential significance for improving high-altitude developmental potential.

Causal role of the pyrimidine deoxyribonucleoside degradation superpathway mediation in Guillain-Barré Syndrome via the HVEM on CD4 + and CD8 + T cells

Immune system regulation is a key indicator of the gut microbiota (GM) influencing disease development. The causal role of the GM in Guillain-Barré syndrome (GBS) and whether it can be mediated by immune cells is unknown. Genome-wide association study (GWAS) summary statistics for the GM were obtained from the Dutch Microbiota Project (n = 7,738) and the FINRISK 2002 (FR02) cohort (n = 5,959). Inverse variance weighting method (IVW) were used as the main method to evaluate the causal relationship between GM and GBS. Subsequently, the mediating effects of 731 immune traits were evaluated. Additionally, we also executed the Bayesian Weighting algorithm for verification. Mendelian randomization (MR) analysis determined the protective effect of the pyrimidine deoxyribonucleoside degradation superpathway on GBS (IVW: P = 0.0019, OR = 0.4508). It is worth noting that in the causal effects of pyrimidine deoxyribonucleoside degradation superpathway on GBS, the mediated proportions of herpesvirus entry mediator (HVEM) ( HVEM on CM CD4 + , HVEM on naive CD4 + , HVEM on CD45RA − CD4 + , HVEM on CM CD8br) in the T cell maturation stage on GBS were -0.0398, -0.0452, -0.0414, -0.0425, accounting for 5.00%, 5.67%, 5.19% and 5.34% of the total effect. 11 types of intestinal bacteria might be involved in the pyrimidine deoxyriboside degradation superpathway, including Staphylococcus A fleurettii, AR31,CAG-274 sp000432155, Photobacterium, Acetobacteraceae, Dysgonomonadaceae, NK4A144,Leptospirae, CAG-81 sp000435795, Leptospirales and CAG-873 sp001701165. This study suggests that there is a causal relationship between pyrimidine deoxyribonucleoside degradation superpathway and GBS, which may be mediated by HVEM on CD4 + and CD8 + T cells. As a bidirectional molecular switch, HVEM plays an important role in T cell regulation. 11 intestinal flora were found to be involved in pyrimidine deoxyribonucleoside degradation superpathway, and their changes may be related to the occurrence of GBS. However, extensive research is still warranted before microbiome sequencing can be used for prevention and targeted treatment of GBS.

Alzheimer's Disease-Derived Outer Membrane Vesicles Exacerbate Cognitive Dysfunction, Modulate the Gut Microbiome, and Increase Neuroinflammation and Amyloid-β Production.

Although our understanding of the molecular biology of Alzheimer's disease (AD) continues to improve, the etiology of the disease, particularly the involvement of gut microbiota disturbances, remains a challenge. Outer membrane vesicles (OMVs) play a key role in central nervous system diseases, but the impact of OMVs on AD progression remains unclear. In this study, we hypothesized that AD-derived OMVs (OMVsAD) were a risk factor in AD pathology. To test our hypothesis, young APP/PS1 mice (AD mice) were given OMVsAD by gavage. Young AD mice were euthanized 120days after gavage to assess the intestinal barrier, gut microbiota diversity, mediators of neuroinflammation, glial markers, amyloid burden, and short-chain fatty acid (SCFA) levels. Our results showed that OMVsAD accelerated cognitive dysfunction after 120days of intragastric administration. Morris water maze experiment and new object recognition test showed that OMVsAD caused significantly poorer spatial ability learning and memory of the AD mice. We observed the OMVsAD-treated APP/PS1 mice display OMVs disrupting the intestinal barrier compared with controls of normal human-derived OMVs. Compared with the OMVsHC group, claudin-5 and ZO-1 related to the intestinal barrier were significantly downregulated in the OMVsAD group. The OMVsAD activate microglia in the cerebral cortex and hippocampus of AD mice, and the levels of IL-1β, IL-6, TNF-α, and NF-Κb were upregulated. We also found that OMVsAD increased Aβ production. 16S rRNA sequencing showed that OMVsAD negatively regulated the α- and β-diversity index of intestinal flora and reduced the levels of SCFA. OMVsAD may change the intestinal flora of young AD, damage the intestinal mucosa and blood-brain barrier, and accelerate AD neuropathological damage.

The Hydrophobic Amino Acid-Rich Fish Collagen Peptide Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice via Repairing the Intestinal Barrier, Regulating Intestinal Flora and AA Metabolism.

The incidence of ulcerative colitis (UC) is increasing annually, but treatment option is limited. Fish collagen peptide (FCP) is a food source collagen peptide that has shown promise in alleviating UC symptoms. However, its impact on the intestinal barrier and intestinal metabolic homeostasis in UC remains unclear. This study aimed to analyze the peptide sequences and absolute amino acid (AA) content of FCP, assessing its effects on UC in mice induced by dextran sulfate sodium (DSS). FCP was examined by liquid chromatography and tandem mass spectrometry (LC-MS/MS) analysis. The 3% DSS was utilized to induce UC in murine models, followed by the assessment of the therapeutic efficacy of FCP. Clinical manifestations of UC mice were meticulously evaluated and scored. Subsequently, samples were procured for histological examination and intestinal epithelial barrier integrity analysis as well as macrogenomic and metabolomic profiling. Here, it shows that abundant peptide sequences and AAs were in FCP, particularly enriched in hydrophobic AAs (HAAs). Furthermore, it was observed that FCP effectively reversed colon shortening and reduced the extent of histological damage. Additionally, FCP suppressed the abnormal expression of inflammatory factors and intestinal barrier proteins and modulated the dysbiosis of gut microbiota toward a balanced state. These alterations led to the activation of intestinal alkaline AA and various AA metabolisms, ultimately contributing to the mitigation of UC symptoms. In summary, the diverse peptide sequences and high AAs in FCP, particularly rich in HAAs, can alleviate DSS-induced UC via preserving intestinal barrier integrity, regulating gut microbiota, and modulating AA metabolism.

Contribution of gut microbiota to the development of Crohn's disease: Insights gained from fecal microbiota transplantation studies in mice.

We would like to present some new thoughts on the publication in the journal published in August 2024 in World Journal of Gastroenterology. We specifically focused on the alterations in the intestinal tract, mesenteric adipose tissue (MAT), and systemic inflammatory changes in mice following fecal flora transplantation into a mouse model of Crohn's disease (CD). Accumulating evidence suggests that the occurrence of CD is influenced by environmental factors, host immune status, genetic susceptibility, and flora imbalance. One microbiota-based intervention, fecal microbiota transplantation, has emerged as a potential treatment option for CD. The MAT is considered a "second barrier" around the inflamed intestine. The interaction between gut microbes and inflammatory changes in MAT has attracted considerable interest. In the study under discussion, the authors transplanted fetal fecal microorganisms from patients with CD and clinically healthy donors, respectively, into 2,4,6-trinitrobenzene sulfonic acid-induced CD mice. The research explored the complex interplay between MAT, creeping fat, inflammation, and intestinal flora in CD by evaluating intestinal and mesenteric lesions, along with the systemic inflammatory state in the mice. This article provides several important insights. First, the transplantation of intestinal flora holds significant potential as a therapeutic strategy for CD, offering hope for patients with CD. Second, it presents a novel approach to the diagnosis and treatment of CD: The inflammatory response in CD could potentially be assessed through pathological or imaging changes in the MAT, and CD could be treated by targeting the inflammation of the MAT.