[Effects of electroacupuncture on the inflammatory response and intestinal flora in obese rats]. / ç”µé’ˆå¯¹è‚¥èƒ–å¤§é¼ å°è‚ ç‚Žæ€§ååº”åŠè‚ é“èŒç¾¤çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) on the expressions of high mobility group protein 1(HMGB1) and myeloid differentiation factor 88 (MyD88) in the small intestine and intestinal flora of obese rats, so as to explore the potential mechanism of EA to improve obesity in rats. METHODS: After 1 week of acclimatization, 10 rats were randomly selected from 50 Wistar male rats as the normal group, and the rest rats were fed with high-fat diet for 8 weeks to establish the obese model. The successfully modeling rats were randomly divided into model group, EA group and sham EA group, with 10 rats in each group. Rats in the EA group were given EA (2 Hz, 1 mA) at "Zhongwan"(CV12), "Guanyuan"(CV4), "Zusanli" (ST36)and "Fenglong"(ST40). Rats in the sham EA group were given shallow stabs at acupoints of the EA group about 5 mm outwardly and the electrodes were clamped without being energized. Both groups were intervened for 10 min each time, 3 times (Monday, Wednesday and Friday) a week for 8 weeks. The body weights of the rats were measured before and after 8 weeks of intervention, respectively. The contents of serum lipopolysaccharide (LPS) and tumor necrosis factor (TNF)-α were measured by ELISA, and the protein and mRNA expressions of HMGB1 and MyD88 in the small intestine were detected by Western blot and real-time quantitative PCR, respectively. 16S rRNA sequencing was performed to determine the relative abundance and diversity of the bacterial flora in the fresh feces of rats. RESULTS: Compared with the normal group, the body weight, serum LPS and TNF-α contents, small intestinal HMGB1 and MyD88 protein and mRNA expression levels of rats in the model group were significantly increased (P<0.01), while the relative abundance of Lactobacillus, Muri and Bifidobacterium was decreased (p<0.01), Collinsella, Prevotella and Ruminococcus was increased (P<0.01). Compared with model group, the body weight, serum LPS and TNF-α contents, protein and mRNA expression levels of HMGB1 and MyD88 in both EA and sham EA groups were decreased (P<0.01, P<0.05), while the relative abundance of Lactobacillus, Muri and Bifidobacterium was increased (P<0.01) and Collinsella, Prevotella and Ruminococcus decreased (P<0.01). Comparison between EA group and sham EA group showed that, the contents of LPS and TNF-α in serum of rats in sham EA group were increased (P<0.01, P<0.05), the relative abundance of Lactobacillus, Muri and Bifidobacterium was lower (P<0.05, P<0.01), and Collinsella, Prevotella and Ruminococcus was higher (P<0.01). CONCLUSIONS: EA can reduce the body weight of obese rats, which may be related to the regulation of the structure of intestinal flora and the reduction of inflammatory reactions in the small intestine.

Effect of Morchella esculenta polysaccharides on the rectal microbiota of mice challenged with lipopolysaccharides.

Introduction: Intestinal dysfunction poses a severe problem by preventing the digestion and absorption of nutrients. The gut, being the most vital organ for these processes, plays a crucial role in ensuring our body receives the nutrients it needs. We explored the mitigating effect of Morchella esculenta polysaccharides (MEP) on intestinal injury induced by lipopolysaccharides (LPS) through the modulation of intestinal flora. Methods: For this purpose, Kunming mice (KM) were divided into three groups, namely, PC, PM, and PY. Group PY was treated with MEP, while groups PM and PY were induced with LPS. Results: The results showed that weight loss in the PM group was significantly greater than that in the PY group (P < 0.05), and the organ indexes of the lung and spleen in the PM group were significantly higher than those in the PC (P < 0.01) and PY (P < 0.05) groups. LPS caused severe injuries in KM mice in the PM group, characterized by broken villi. However, MEP treatment could alleviate this damage in the PY group, resulting in relatively intact villi. The serum analysis showed that tumor necrosis factor alpha (TNF-ɑ) (P < 0.01), interleukin 6 (IL-6) (P < 0.01), and 3,4-methylenedioxyamphetamine (MDA) (P < 0.05) levels were significantly higher in the PM group, while IL-10 (P < 0.001), superoxide dismutase (SOD) (P < 0.01) and glutathione peroxidase (GSH-Px) (P < 0.01) were significantly lower in that group. Interestingly, supplementation with MEP could lower the levels of TNF-ɑ, IL-10, IL-6, MDA while increasing the levels of superoxide dismutase (SOD) (P < 0.01) and GSH-Px. The gut microbiota analysis yielded 630,323 raw reads and 554,062 clean reads, identifying 3,390 amplicon sequencing variants (ASVs). One phylum and five genera were notably different among animal groups, including Escherichia_Shigella, Limosilactobacillus, unclassified_Geminicoccaceae, unclassified_Rhodobacteraceae, and Parabacteroides (P. distasonis). Discussion: In conclusion, we found that MEP could mitigate the intestinal damage caused by LPS by modulating the inflammatory response, oxidative resistance, and intestinal flora of KM mice. Our results may provide insights into novel treatment options for intestine-related diseases.

Regulation of colon injury and improvement of exercise performance in exhausted running mice by Lactobacillus pentosus CQZC02.

In this study, strenuous forced exercise caused intestinal damage and reduced the exercise capacity of mice. However, the antioxidant and anti-inflammatory properties of Lactobacillus pentosus CQZC02 (LPCQZC02) were found to improve both the intestinal barrier and exercise function in mice. The effectiveness of LPCQZC02 was confirmed through various methods, including kit detection, pathological observation, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and intestinal flora analysis. The findings demonstrated that LPCQZC02 could control colonic index, lessen colonic enlargement caused by intense exercise, and extend the running duration of mice. Serum levels of total superoxide dismutase (T-SOD), glutathione (GSH), and interleukin-10 (IL-10) were elevated, whereas those of malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were reduced. The findings of the mRNA expression analysis revealed that in the colons of mice who remarkably exercised, LPCQZC02 could increase the expression levels of zonula occludens-1 (ZO-1), occludin-1, and claudin-1 genes. Additionally, in skeletal muscle tissue, it could downregulate TNF-α expression level and upregulate copper/zinc superoxide dismutase (Cu/Zn-SOD) and manganese superoxide dismutase (Mn-SOD) expression levels. Furthermore, LPCQZC02 could both reduce and promote beneficial bacteria in the intestines of mice undergoing intense exercise. In conclusion, LPCQZC02 emerged as a functional probiotic and demonstrated a notable advantage over sulfasalazine, a medication for intestinal conditions, in mitigating oxidative inflammation, repairing intestinal barrier damage, and enhancing motor function in mice subjected to strenuous exercise.

Bacterial Lysate-Based Bifunctional mRNA Nanoformulation for Efficient Colon Cancer Immunogene Therapy.

mRNA-based nonviral gene therapy has played an important role in cancer therapy, however, the limited delivery efficiency and therapeutic capacity still require further exploration and enhancement. Immunogene therapy provides a strategy for cancer treatment. Bacteria are tiny single-celled living organisms, many of which can be found in and on the human body and are beneficial to humans. Lactobacillus reuteri is a bacterial member of the gut flora, and recent research has shown that it can reduce intestinal inflammation by stimulating an immunomodulatory response. L. reuteri lysate represents an ideal resource for constructing advanced mRNA delivery systems with immune stimulation potential. Here, we prepared a bifunctional mRNA delivery system DMP-Lac (DOTAP-mPEG-PCL-L. reuteri lysate), which successfully codelivered L. reuteri lysate and IL-23A mRNA, exhibited a high mRNA delivery efficiency of 75.56% ± 0.85%, and strongly promoted the maturation and activation of the immune system in vivo. Both the CT26 abdominal metastasis model and the lung metastasis model also exhibited a good therapeutic effect, and the tumor inhibition rate of DMP-Lac/IL-23A group reached 97.92%. Protein chip technology verified that DMP acted as an immune adjuvant, demonstrating that the L. reuteri lysate could regulate the related immune cells, while IL-23 mRNA caused changes in downstream factors, thus producing the corresponding tumor treatment effect. The DMP-Lac/IL-23A complex exhibited strong anticancer immunotherapeutic effects. Our results demonstrated that this bifunctional mRNA formulation served as a tumor-specific nanomedicine, providing an advanced strategy for colon cancer immunogene therapy.

Activation of GABABR Attenuates Intestinal Inflammation by Reducing Oxidative Stress through Modulating the TLR4/MyD88/NLRP3 Pathway and Gut Microbiota Abundance.

Oxidative stress emerges as a prominent factor in the onset and progression of intestinal inflammation, primarily due to its critical role in damaging cells and tissues. GABAergic signaling is important in the occurrence and development of various intestinal disorders, yet its effect on oxidative stress remains unclear. We attempted to assess whether GABAergic signaling participated in the regulation of oxidative stress during enteritis. The results showed that lipopolysaccharide (LPS) significantly decreased γ-aminobutyric acid (GABA) levels in the ileal tissues of mice. Interestingly, the application of GABA significantly repressed the shedding of intestinal mucosal epithelial cells and inflammatory cell infiltration, inhibited the expressions of proinflammatory factors, including granulocyte colony-stimulating factor and granulocyte-macrophage colony stimulating factor, and enhanced the levels of anti-inflammatory cytokines interleukin (IL)-4 and IL-10, indicating that GABA could alleviate enteritis in mice. This observation was further supported by transcriptome sequencing, revealing a total of 271 differentially expressed genes, which exhibited a marked enrichment of inflammatory and immune-related pathways, alongside a prominent enhancement of GABA B receptor (GABABR) signaling following GABA administration. Effectively, Baclofen pretreatment alleviated intestinal mucosal damage in LPS-induced mice, suppressed proinflammatory cytokines IL-1ß, IL-6, and tumor necrosis factor alpha expressions, and boosted total antioxidant capacity, superoxide dismutase (SOD), and glutathione (GSH) levels. Moreover, Baclofen notably enhanced the viability of LPS-stimulated IPEC-J2 cells, contracted the proinflammatory secretion factors, and reinforced SOD, GSH, and catalase levels, emphasizing the anti-inflammatory and antioxidant effects associated with GABABR activation. Mechanistically, Baclofen restrained the mRNA and protein levels of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3), and inducible nitric oxide synthase, while elevating nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 in both mice and IPEC-J2 cells, indicating that activating GABABR strengthened antioxidant abilities by interrupting the TLR4/MyD88/NLRP3 pathway. Furthermore, 16S rDNA analysis demonstrated that Baclofen increased the relative abundance of probiotic, particularly Lactobacillus, renowned for its antioxidant properties, while reducing the relative richness of harmful bacteria, predominantly Enterobacteriaceae, suggesting that GABABR signaling may have contributed to reversing intestinal flora imbalances to relieve oxidative stress in LPS-induced mice. Our study identified previously unappreciated roles for GABABR signaling in constricting oxidative stress to attenuate enteritis, thus offering novel insights for the treatment of intestinal inflammation.

Structural characterization of an acid-extracted polysaccharide from Suillus luteus and the regulatory effects on intestinal flora metabolism in tumor-bearing mice.

Suillus luteus is an excellent edible fungus that has been applied in soil remediation and environmental pollution control, while the development of bioactive polysaccharide component including structural performance and intestinal flora regulation is still insufficient. In this study, a S. luteus acid-extracted polysaccharide (SLAP) was prepared under room temperature, then the structural characteristics and regulatory effects on gut microbiota metabolism in tumor-bearing mice were investigated. Results showed that SLAP was a kind of gulcomannan (average molecular weight of 1.76 × 107 Da) comprised of Xyl, Man, Glc, Gal (molar ratio of 0.19:1.00:0.72:0.53), which took ß-(1 â†’ 4)-Manp and ß-(1 â†’ 4)-Glcp as the backbone with ß-(1 â†’ 6)-Glcp and α-(1 â†’ 6)-Galp as branches. The animal experiment results demonstrated that SLAP could effectively enhance the immunoregulatory activities of CD4+ and CD8+ T cells in tumor-bearing mice via improving intestinal lactobacillaceae contents and promoting primary bile acids biosynthesis, finally leading to the suppression of solid tumors growth with an inhibitory rate of 61.14 % (100 mg/kg·d). These results would provide certain data support and research basis for further applications of SLAP as an immunomodulatory adjuvant in food and medicine fields.

Ganoderma lucidum spore powder after oil extraction alleviates microbiota dysbiosis to improve the intestinal barrier function in mice.

BACKGROUND: There are few studies about the differences in the composition of moisture, ash, crude protein, crude fat, crude polysaccharide and ergothioneine in Ganoderma lucidum spore powder (GLSP) from different origins. As for GLSP after oil extraction (OE-GLSP), there are still lots of bioactive substance in it. It can be seen that OE-GLSP has certain biological activity. The effect of OE-GLSP on the improvement of intestinal barrier function has been less studied. RESULTS: The results showed that there were significant differences for GLSP from five different origins (Anhui, Jilin, Jiangxi, Shandong and Zhejiang) in moisture (0.065-0.113%), ash (0.603-0.955%), crude fat (42.444-44.773%), crude polysaccharide (2.977-4.127%), crude protein (14.761-17.639%) and ergothioneine (0.552-1.816 mg g-1) (P < 0.05). The monosaccharides of GLSP polysaccharide mainly consist of glucose, galactose, mannose, rhamnose, etc. Moreover, the effects of OE-GLSP supplementation on the regulation of organ index, colonic tissue and intestinal microbiota in C57BL/6J mice were investigated. The supplement of OE-GLSP could restore the organ index and weight loss of antibiotic-treated mice. Moreover, OE-GLSP led to the improvement of intestinal dysbiosis by enriching Bacteroidetes, Firmicutes, Lactobacillus and Roseburia, and increasing the Firmicutes/Bacteroidetes ratio. In addition, OE-GLSP intervention repaired intestinal barrier dysfunction by increasing the expression of tight junction proteins (Occludin, Claudin-1 and E-cadherin). CONCLUSION: Different GLSP from five origins exhibited significant differences in microstructure and contents of crude polysaccharide, crude protein, crude fat, water, ash and ergothioneine. Moreover, it was found that OE-GLSP could improve the intestinal barrier function and induce potentially beneficial changes in intestinal flora. © 2024 Society of Chemical Industry.

Research progress of probiotics regulating intestinal micro-ecological environment in obese patients after bariatric surgery. / ç›Šç”ŸèŒè°ƒèŠ‚è‚¥èƒ–æ‚£è€ å‡é‡æœ¯åŽè‚ é“å¾®ç”Ÿæ€çŽ¯å¢ƒçš„ç ”ç©¶è¿›å±•.

Bariatric surgery may cause intestinal microecological environment imbalance due to changes in gastrointestinal anatomy. Some patients may have complications, even regain weight. Probiotics can act on intestinal mucosa, epithelium and gut-associated lymphoid tissue to improve the intestinal microecological environment of obese patients after bariatric surgery. Probiotics can promote the production of intestinal antibacterial substances, bind specifically to receptors, decrease intestinal pH value, reduce the inflammatory factors, thus helping patients lose weight and lower blood sugar levels after bariatric surgery. Probiotics can produce lactic acid, acetic acid, lactase, etc., inhibit the growth of harmful bacteria, improve gastrointestinal symptoms of patients after bariatric surgery. Probiotics can activate the AMP-activated protein kinase signaling pathway, improve lipid metabolism, and promote the recovery of symptom indicators of nonalcoholic fatty liver disease after bariatric surgery. Probiotics can regulate the release of neurotransmitters or metabolites by the microbiota through the gut-brain axis to affect brain activity and behavior, thus helping patients improve bad mood after bariatric surgery. This article describes the intestinal microecological environment of obese patients and the change mechanism after bariatric surgery and summarizes the effects and possible mechanisms of probiotics in improving the intestinal microecological environment of obese patients after bariatric surgery, in order to provide references for promoting the clinical application of probiotics.

Potential prebiotic properties and proliferation mechanism of fermented milk-derived polypeptides.

The purpose of this paper is to investigate the potential prebiotic properties and proliferation mechanism of fermented milk-derived peptides. In this study, fermented milk-derived polypeptides were obtained by extraction, separation, and purification. The purified peptides were used to culture fecal flora in vitro, and the relative abundance and composition of the flora were analyzed by high-throughput 16S rRNA sequencing technology. The results showed that peptides can promote the proliferation of beneficial bacteria Lactococcus in the intestine and inhibit the proliferation of harmful bacteria Escherichia coli-Shigella. The amino acid sequence of polypeptide components was determined and synthesized in vitro to verify the proliferation of intestinal flora; the proliferation mechanism of peptides on Lactococcus lactis was studied using non-targeted LC-MS metabolomics technology. Five important peptides with molecular weights of 1000-2000 Da were identified by LC-MS: GRP1 (LTEEEK), GRP2 (ENDAPSPVM*K), GRP3 (ITVDDK), GRP4 (EAM*APK) and GRP5 (LPPPEK). The results showed that the peptides could affect the arginine biosynthesis pathway and the amino sugar and nucleotide sugar metabolism of Lactococcus lactis. In addition, the peptides increased the expression of organic acids and their derivatives in Lactococcus lactis. This study provides a research basis for expanding the potential sources of new prebiotics and also opens up a new idea for discovering new prebiotics in vitro.

A New Strategy for Dietary Nutrition to Improve Intestinal Homeostasis in Diarrheal Irritable Bowel Syndrome: A Perspective on Intestinal Flora and Intestinal Epithelial Interaction.

BACKGROUND AND OBJECTIVES: Although a reasonable diet is essential for promoting human health, precise nutritional regulation presents a challenge for different physiological conditions. Irritable Bowel Syndrome (IBS) is characterized by recurrent abdominal pain and abnormal bowel habits, and diarrheal IBS (IBS-D) is the most common, seriously affecting patients' quality of life. Therefore, the implementation of precise nutritional interventions for IBS-D has become an urgent challenge in the fields of nutrition and food science. IBS-D intestinal homeostatic imbalance involves intestinal flora disorganization and impaired intestinal epithelial barrier function. A familiar interaction is evident between intestinal flora and intestinal epithelial cells (IECs), which together maintain intestinal homeostasis and health. Dietary patterns, such as the Mediterranean diet, have been shown to regulate gut flora, which in turn improves the body's health by influencing the immune system, the hormonal system, and other metabolic pathways. METHODS: This review summarized the relationship between intestinal flora, IECs, and IBS-D. It analyzed the mechanism behind IBS-D intestinal homeostatic imbalance by examining the interactions between intestinal flora and IECs, and proposed a precise dietary nutrient intervention strategy. RESULTS AND CONCLUSION: This increases the understanding of the IBS-D-targeted regulation pathways and provides guidance for designing related nutritional intervention strategies.

[Effect of Modified Xiaoyao Powder on intestinal barrier and intestinal flora in mice with metabolic associated fatty liver disease based on "gut-liver axis"].

This study explores the effects and mechanisms of Modified Xiaoyao Powder on the intestinal barrier and intestinal flora in mice with metabolic associated fatty liver disease(MAFLD) based on the " gut-liver axis". Sixty male C57BL/6 mice were randomly divided into the normal group, model group, bifidobacterium tetrad tablet group(SQ), and Modified Xiaoyao Powder groups with low,medium and high doses(XL, XM, XH), with 10 mice in each group. All the mice were administrated with a high-fat diet to build the MAFLD model except the normal group and then treated with related drugs for 12 weeks. Body mass, liver wet weight, and liver index were detected. Serum aspartate aminotransferase(AST), alanine aminotransferase(ALT), total cholesterol(TC), triacylglycerol(TG), low density lipoprotein cholesterol(LDL-C), high density lipoprotein cholesterol(HDL-C), and lipopolysaccharide(LPS)levels were detected using the biochemical kits. The contents of tumor necrosis factor-α(TNF-α) and interleukin(IL-6) in the liver were tested simultaneously. The morphological changes of the liver and intestine were observed using hematoxylin-eosin(HE) staining and oil red O staining. The goblet cells in the ileum were detected by periodic acid Schiff and alcian blue stain(AB-PAS) staining.The expression of zonula occludens-1(ZO-1), recombinant occludin(occludin), and recombinant claudin 1(claudin-1) in ileum and colon were detected by immunohistochemistry and Western blot. The changes of intestinal flora in mice were analyzed by 16S rRNA gene sequencing. The results showed that compared with the normal group, body weight, liver wet weight and liver index in the model group increased. The contents of TC, TG, ALT, AST, LDL-C, and LPS in the serum of the model group increased, while HDL-C decreased. Meanwhile, the contents of TNF-α and IL-6 in liver tissue increased and liver lipid accumulation increased, indicating successful model induction. Compared with the model group, body weight, liver wet weight, and liver index were decreased in XM,XH groups and SQ group. Serum levels of TC, TG, LDL-C, ALT and AST in XM group and SQ group were significantly decreased,and HDL-C levels were increased. The levels of IL-6, TNF-α in liver tissue and serum LPS in the XL, XM groups and SQ group were significantly decreased. The protein expression of claudin-1, occludin and ZO-1 in XL, XM groups and SQ group were increased. The analysis of intestinal flora showed that compared with the model group, Modified Xiaoyao Powder with a medium dose could significantly improve the richness and diversity of intestinal flora in mice. At the phylum level, the Firmicutes/Bacteroidetes(F/B) ratio decreased; at the genus level, Lactobacillus, Brautella, Bacteroides, and Ackermannia increased, while Prevotella, Desulfovibrio and Turicibacter decreased. The main differential species were Odorbacteraceaeae and Peptostreptococcaceae. In conclusion, Modified Xiaoyao Powder could inhibit inflammation, regulate intestinal flora homeostasis, and promote the repair of the intestinal mucosal barrier in mice with MAFLD.

Pickle water ameliorates castor oil-induced diarrhea in mice by regulating the homeostasis of the gut microbiota and intestinal mucosal barrier.

Introduction: Diarrhea is a common clinical condition that can potentially be fatal. Current treatment options often have side effects, such as constipation and vomiting, and there remains a need for more effective therapies. Pickled vegetables, a famous traditional food in China, have been suggested in clinical studies to alleviate diarrhea in children, particularly through the use of pickle water (PW). However, the pharmacological effects and mechanisms of PW on intestinal health remain unclear. This study aimed to explore the protective effects of PW on castor oil-induced diarrhea in ICR mice and to investigate its potential mechanisms. Methods: To evaluate the antidiarrheal effects of PW, we used a castor oil-induced diarrhea model in ICR mice. Various indices were measured to assess the severity of diarrhea. After euthanizing the mice, oxidative stress markers in the ileum were assessed using biochemical methods, and the expression of tight junction-related proteins in the ileum was analyzed using Western blot. Additionally, 16S rRNA high-throughput sequencing was used to evaluate the diversity and composition of the intestinal flora. Results: The results showed that PW supplementation reduced body weight without significantly affecting organ index and liver function in the castor oil-induced diarrhea mice. PW also effectively reduced the dilution rate, diarrhea index, average loose stool grade, propelling distance of carbon powder, and intestinal propulsive rate while improving the pathological abnormality in the ileum. Furthermore, PW enhanced the activities of total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-PX), and catalase (CAT) while reducing malonaldehyde (MDA) levels. PW also increased the expression of tight junction proteins zonula occludens-1 (ZO-1) and occludin in the ileum. Additionally, the analysis of 16S rDNA revealed that PW increased both α and ß diversity, improved the composition of the intestinal flora, and restored it to a normal level. Discussion: Collectively, dietary PW administration ameliorates Castor oil-induced diarrhea by restoring tight junctions between intestinal mucosal cells, suppressing oxidative stress, and regulating the composition of intestinal flora. These findings suggest that PW may be a promising strategy for managing diarrhea.

Research progress on the correlation between intestinal flora and colorectal cancer.

Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies in the world. With the rapid pace of life and changes in diet structure, the incidence and mortality of CRC increase year by year posing a serious threat to human health. As the most complex and largest microecosystem in the human body, intestinal microecology is closely related to CRC. It is an important factor that affects and participates in the occurrence and development of CRC. Advances in next-generation sequencing technology and metagenomics have provided new insights into the ecology of gut microbes. It also helps to link intestinal flora with CRC, and the relationship between intestinal flora and CRC can be continuously understood from different levels. This paper summarizes the relationship between intestinal flora and CRC and its potential role in the diagnosis of CRC providing evidence for early screening and treatment of CRC.

Theaflavins mitigate diabetic symptoms in GK rats by modulating the INSR/PI3K-Akt/GSK-3 pathway and intestinal microbiota.

Dietary management and interventions are crucial in the clinical management of diabetes. Numerous active dietary components in black tea have demonstrated positive effects on blood glucose levels and metabolic functions. However, limited research has explored the potential of theaflavins (TF), polyphenols in black tea, for diabetes management. In this study, high-purity TF was administered to Goto-Kakizaki (GK) diabetic model rats for four weeks to investigate its impact on diabetic pathology and analyze the underlying mechanisms through liver transcriptomics, hepatocyte metabolomics, and gut microbiome analysis. The findings indicated that continuous administration of TF (100 mg/kg) significantly suppressed blood glucose levels, reduced insulin resistance, and decreased the expression of oxidative stress indicators and inflammatory factors in GK rats. Further analysis revealed that TF might alleviate insulin resistance by improving hepatic glycogen conversion and reducing hepatic lipid deposition through modulation of key pathways, such as peroxisome proliferator-activated receptors and PI3K/AKT/GSK-3 pathways within the liver, thereby ameliorating diabetic symptoms. Additionally, TF intake facilitated the restoration of the intestinal microbial community structure by reducing the abundance of harmful bacteria and increasing the abundance of beneficial bacteria. It also reduced endotoxin lipopolysaccharide production, thereby lowering the chances of insulin resistance development and enhancing its efficacy in regulating blood glucose levels. These findings offer a novel perspective on the potential of black tea and its active constituents to prevent and treat diabetes and other metabolic disorders, providing valuable references for identifying and applying active dietary components from tea.

In vivo toxicity of upconversion nanoparticles (NaYF4:Yb, Er) in zebrafish during early life stages: Developmental toxicity, gut-microbiome disruption, and proinflammatory effects.

Lanthanide-doped upconversion nanoparticles (Ln-UCNPs) have been considered promising materials for various fields, such as biomedical and industrial applications. However, data and reports regarding its toxicity and environmental risks are scarce. Under these circumstances, data must be obtained to fully understand potential toxicity and adverse outcome pathways. In the present study, the toxicity of uncoated Ln-UCNP cores (NaYF4:Yb, Er) was systematically assessed in zebrafish embryos during early developmental stages. Ln-UCNPs were found to have multiple toxic effects, such as effects on survival rates, delayed hatching times, shorter body lengths, altered heart rates and blood circulation (significantly reduced), and neurobehavioral impairments in response to photoperiod stimulation. Bioimaging showed that Ln-UCNPs were distributed on the chorion, eyes, and skin at 72 hpf. However, it accumulates in the pharynx, esophagus, and intestine after oral administration. Ln-UCNPs disrupt the diversity and abundance of host-associated microorganisms (gut microbiota) leading to an increase in the prevalence of harmful bacteria in zebrafish. Transcriptomic and Ingenuity Pathway Analysis (IPA) predicted Interleukin-8 (IL-8) signaling, neuroinflammation, cardiac hypertrophy signaling pathways, immune and inflammation-related response interferon-gamma (ifnγ), and miR-155 as key mediators in regulatory effects. Based on this, a causal network was built showing the strong links between the induced gene expression of differentially expressed genes (DEGs), such as nitric oxide synthase 2 (nos2) and tumor necrosis factor (tnf) upon Ln-UCNPs treatment, and with the downstream adverse outcomes, in particular, the promotion of apoptosis, liver damage, and inflammatory response. Finally, RT-qPCR analysis confirmed the up-regulated expression of nos2 and tnf in the exposed larvae, consistent with the observation of an increased number of fluorescence-labelled neutrophils and macrophages in lyz: DsRed transgenic zebrafish until 120 hpf exposure, which together demonstrated the proinflammatory effects of Ln-UCNPs on organisms. In conclusion, we illustrated the developmental toxicity, disruption of gut-microbiome, and proinflammatory effects of Ln-UCNP cores on zebrafish, and the causal network from IPA analysis may help further elucidate the adverse outcome pathway of Ln-UCNPs.

Structural characteristics and intestinal flora metabolism mediated immunoregulatory effects of Lactarius deliciosus polysaccharide.

Lactarius deliciosus, a widely appreciated mushroom with delightful tastes and texture, has exhibited immunomodulatory activity in vitro, while the effects on intestinal flora metabolisms in vivo are ambiguous. In this study, a L. deliciosus polysaccharide (LDP) was extracted and purified, and the structural characteristics were evaluated, as well as the immunological enhancement on tumor-bearing mice through regulating intestinal flora metabolisms. Results showed that LDP was a heteropolysaccharide (average molecular weight of 1.44 × 107 Da) with a backbone of α-(1 â†’ 6)-Manp and branches of α-(1 â†’ 6)-Galp, α-(1 â†’ 3)-Fucp, α-(1 â†’ 6)-Glcp, α-(1 â†’ 4)-Glcp. Animal experiments indicated that LDP could significantly protect immune organs of tumor-beraing mice and suppress solid tumors growth with inhibitory rate of 51.61 % (high-dose, 100 mg/kg), and improve the intestinal lactobacillus contents, promote adenine mediated zeatin biosynthesis, then competitively antagonize A2A receptor and enhance the activities of CD4+ T cells and CD8+ T cells, finally effectively facilitate the apoptosis and elimination of tumor cells. These results would provide powerful data supports for the further antitumor mechanisms development and practical applications of L. deliciosus polysaccharide in food and drug industries.

Shengmai San formula alleviates high-fat diet-induced obesity in mice through gut microbiota-derived bile acid promotion of M2 macrophage polarization and thermogenesis.

BACKGROUND: Shengmai San Formula (SMS) is a traditional Chinese medicine (TCM) that has been used to treat wasting-thirst regarded as diabetes mellitus, which occurs disproportionately in obese patients. Therefore, we investigated whether SMS could be used to treat obesity, and explored possible mechanisms by which it might improve glucose and fat metabolism. METHODS: To investigate the effects of SMS on a high-fat diet (HFD)-induced obesity (DIO) model, we studied glucose metabolism via glucose tolerance testing (GTT) and insulin tolerance testing (ITT). Browning of white adipose tissue (WAT) was evaluated using H&E staining, along with browning-related gene and protein expression. Changes in bile acid (BA) levels in serum, liver, ileum, and inguinal white adipose tissue were detected by Ultra performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). In addition, antimicrobial mixture (ABX) and fecal microbial transplantation (FMT) experiments were used to verify the role of gut flora in the effects produced by SMS on HFD-induced obesity model. RESULTS: SMS ameliorated diet-induced dyslipidemia in a dose-dependent manner and reduced glucose intolerance and insulin resistance in DIO mice, helping to restore energy metabolism homeostasis. SMS significantly altered the structure of intestinal microbiome composition, decreasing the abundance of Lactobacillus carrying bile salt hydrolase (BSH) enzymes and thereby increasing the level of conjugated BAs in the blood, ileum, and iWAT. Increased TCA content promoted the secretion of Slit3 from M2 macrophages in iWAT, which activates the protein kinase A/calmodulin-dependent protein kinase II (PKA/CaMKII) signaling pathway in sympathetic neurons via the roundabouts receptor 1(ROBO1). This pathway promotes the synthesis and release of norepinephrine (NE), inducing cyclic adenosine monophosphate (cAMP) release in adipose tissue that activates the cyclic adenosine monophosphate/protein kinase A/phosphorylated hormone-sensitive lipase (cAMP/PKA/pHSL) pathway and enhances WAT browning. ABX treatment eliminated SMS effects on glucose and lipid metabolism in DIO mice, whereas glucose and lipid metabolism in obese mice improved following SMS-FMT and increased the level of serum bile acids. CONCLUSION: SMS affects intestinal flora and bile acid composition in vivo and increased TCA promotes M2 macrophage polarization and Slit3 release in adipose tissue. This induces NE release and increases WAT browning in obese mice, which may be a mechanism by which SMS could be used to treat obesity.

Quercetin intervention mitigates small intestinal damage and immunologic derangement induced by polystyrene nanoplastics: Insights from multi-omics analysis in mice.

Nanoplastics (NPs), which belong to emerging environmental pollutants, threaten environmental sustainability and human health. Despite recent studies have reported that NPs damage the gastrointestinal tract and immune homeostasis, the underlying mechanisms remain unclear. Polyphenols have been found to promote NPs excretion by interacting with intestinal flora (IF). However, the potential mechanisms and action targets of this are still poorly understood. To address these knowledge gaps, we investigated the impact of quercetin and three concentrations of polystyrene nanoplastics (PS-NPs) in mice using an integrated phenotypic and multi-omics analysis. Our findings demonstrated that PS-NPs accumulate within the intestine, resulting in impairments to intestinal tissue and barrier function, as well as disturbing the expression of immune-response small intestinal genes and composition of IF. Exposure to PS-NPs significantly elevate the level of intestinal IgG and CD20+ B cells, while inhibiting T cells activation. Furthermore, PS-NPs could induce systemic immune and serum insulin level disorders. Quercetin might mitigate PS-NPs-induced intestinal damage and immune disorders though reversing IF disorders, gene expression changes, and their interaction.

Berberine attenuates 5-fluorouracil-induced intestinal mucosal injury by modulating the gut microbiota without compromising its anti-tumor efficacy.

Background: 5-Fluorouracil (5-Fu), a prominent chemotherapeutic agent for colorectal cancer (CRC) treatment, is often associated with gastrointestinal toxicities, particularly diarrhea. Our previous study demonstrated that berberine (BBR) ameliorates 5-Fu-induced intestinal mucosal injury by modulating the gut microbiota in rats. Nevertheless, the precise molecular mechanism underlying BBR's protective effect on intestinal mucosa remains elusive, and its impact on the anti-tumor efficacy of 5-Fu warrants further investigation. Methods: The effect of BBR on 5-Fu-induced intestinal mucosal injury was investigated using a tumor-bearing murine model, employing H&E staining, 16 S rDNA sequencing, transcriptome sequencing, Western blot analysis, cell experiments and constructing a pseudo-germ-free tumor xenograft model. Result: Our findings demonstrate that BBR alleviates intestinal mucosal damage, reduces the levels of inflammatory factors (IL-6, TNF-α, and IL-1ß), and inhibits epithelial cell apoptosis in 5-Fu-treated mice without compromising 5-Fu's anti-tumor efficacy. Moreover, 16 S rDNA sequencing indicated that BBR significantly increases the abundance of Akkermansia and decreases the abundance of pathogenic bacteria Escherichia/Shigella at the genus level. Mechanistically, transcriptome sequencing and Western blot analysis confirmed that BBR upregulates PI3K/AKT/mTOR expression in the intestinal mucosa. However, this effect was not observed in tumor tissues. Notably, BBR did not demonstrate a direct protective effect on 5-Fu-treated CCD841 and SW480 cells. Additionally, BBR had no effect on the PI3K/AKT/mTOR pathway in the intestinal tissue of the 5-Fu-treated mouse model with a depleted gut microbiota. Conclusion: This study indicates that BBR alleviates 5-Fu-induced intestinal mucosal injury by modulating the gut microbiota and regulating the PI3K/AKT/mTOR signaling pathway without compromising the anti-tumor efficacy of 5-Fu.

Jianpi Huayu Prescription Prevents Atherosclerosis by Improving Inflammation and Reshaping the Intestinal Microbiota in ApoE-/- Mice.

This study established an LPS-induced RAW264.7 macrophage inflammatory injury model and an AS mouse vulnerable plaque model to observe the effect of JPHYP on macrophage inflammation, plaque formation, blood lipids, inflammation levels, intestinal flora and the influence of TLR4/MyD88/MAPK pathway, and explore the anti-AS effect and molecular mechanism of JPHYP, and detected 16S rRNA of mice intestinal microbes. The difference of intestinal flora in different groups of mice was compared to further explore the intervention effect of JPHYP and clarify the molecular biological mechanism of JPHYP in preventing and treating AS by regulating TLR4/MyD88/MAPK inflammatory signaling pathway and improving intestinal flora.