Improved Gut Microbiota Research Articles

Si–Ni-San improves experimental colitis by favoring Akkermensia colonization

Ethnopharmacological relevanceUlcerative colitis (UC) is widely believed to be a leading risk factor of colorectal cancer. Gut microbiota is a known vital player in the progression of UC. Si–Ni-San (SNS) has been considered to effectively treat colitis in clinical practice during thousands of years, yet whether SNS ameliorated acute colitis mouse model by modulating intestinal flora has not been distinctly elucidated. Aim of the studyOur study aimed to elucidate the effect of SNS against acute murine colitis and focused on the underlying mechanisms of SNS targeting gut microbiota. Materials and methods16S RNA sequencing, molecular biological analysis, and fecal microbiota transplants (FMT) were conducted to reveal the mechanisms of SNS in regulating gut microbiota. ResultsIn our study, SNS dramatically inhibited DSS-induced acute inflammatory responses by improving gut microbiota dysbiosis, as evidenced by decreased abundance proinflammatory species, upregulated abundance of anti-inflammatory species and potentially altered microbiota metabolite metabolism. Additionally, intestinal flora knockout and FMT experiments confirmed that the therapeutic effect of SNS on colitis was dependent on gut microbiota, and specifically on favoring the growth of potential probiotics, Akkermansia genus. Furthermore, we found that SNS alone and SNS combined with Akkermansia muciniphila (A. muciniphila) increased Mucin 2 (MUC2) production, thus enhancing the competitive edge of A. muciniphila among pathogenic gut microbiota. ConclusionOur study shed lights on the underlying mechanism of SNS in attenuating acute murine colitis from the perspective of intestinal flora and provides novel insights into the discovery of adjacent therapeutic strategy against colitis based on SNS and probiotics. ClassificationGastro-intestinal system

Mineralocorticoid receptor blockade improved gut microbiota dysbiosis by reducing gut sympathetic tone in spontaneously hypertensive rats

Microbiota has a crucial role in the host blood pressure (BP) regulation. The present study analyzes whether the mineralocorticoid receptor antagonist spironolactone ameliorates the dysbiosic state in a genetic model of neurogenic hypertension. Twenty-week-old male Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were randomly allocated into three groups: untreated WKY, untreated SHR, and SHR treated with spironolactone for 5 weeks. Spironolactone restored the Firmicutes/Bacteroidetes proportion, and acetate-producing bacteria populations to WKY levels. Spironolactone reduced the percentage of intestinal aerobic bacteria. The amelioration of gut dysbiosis was linked to a reduction in the gut pathology, an enhanced colonic integrity, a reduced gut permeability and an attenuated sympathetic drive in the gut. Spironolactone was unable to reduce neuroinflammation and oxidative stress in the paraventricular nuclei in the hypothalamus. Spironolactone reduced the higher Th17 cells proportion in mesenteric lymph nodes and Th17 infiltration in aorta, improved aortic endothelial function and reduced systolic BP. This study demonstrates for the first time that spironolactone reduces gut dysbiosis in SHR. This effect could be related to its capability to improve gut integrity and pathology due to reduced sympathetic drive in the gut.

Structural characteristics and ameliorative effect of a polysaccharide from Corbicula fluminea industrial distillate against acute liver injury induced by CCl4 in mice

Corbicula fluminea distillate as an important industrial by-product of C. fluminea during steaming process is rich in amino acids, proteins and polysaccharides, showing potential hepatoprotective effect. In this study, a polysaccharide (CFDP) was obtained from C. fluminea distillate by three-phase partitioning combined with (NH4)2SO4 precipitation at a saturation of 60 %. The structural characteristics, antioxidant activity in vitro, and hepatoprotection against mice CCl4-induced acute liver damage of CFDP were studied. Results demonstrated that CFDP was a water-soluble homogenous polysaccharide predominantly comprising glucose (>98 %), with a weight-average molecular weight of 1.4 × 107 Da, and exhibiting potent antioxidant benefits in vitro. CFDP had a backbone of (1 → 4)-α-d-glucopyranosyl (Glcp) and a small amount of (1 → 4, 6)-α-D-Glcp. The branch formed at C-6 comprised by (1→)-α-D-Glcp and (1→)-α-D-N-acetylglucosamine. CFDP possessed excellent hepatoprotective activity against acute liver damage caused by CCl4 in mice, mainly by ameliorating weight reduction and organ injures, alleviating hepatic function and serum lipid metabolism, suppressing oxidative stress and inflammatory responses, as directly verified by histopathological examination. Moreover, CFDP improved gut microbiota by up-regulating the relative abundance of total bacteria and probiotics such as Firmicutes, Bacteroidete, Rumminococcaceae, Lactobacillaceae, accompanied by promoting short chain fatty acid production. Therefore, our findings indicated that CFDP can be developed as a healthy food supplement for the prevention of chemical livery injury.

Gut-Spleen Axis: Microbiota via Vascular and Immune Pathways Improve Busulfan-Induced Spleen Disruption.

Fecal microbiota transplantation (FMT) is an effective means of modulating gut microbiota for the treatment of many diseases, including Clostridioides difficile infections. The gut-spleen axis has been established, and this is involved in the development and function of the spleen. However, it is not understood whether gut microbiota can be used to improve spleen function, especially in spleens disrupted by a disease or an anti-cancer treatment. In the current investigation, we established that alginate oligosaccharide (AOS)-improved gut microbiota (A10-FMT) can rescue anticancer drug busulfan-disrupted spleen vasculature and spleen function. A10-FMT improved the gene and/or protein expression of genes involved in vasculature development, increased the cell proliferation rate, enhanced the endothelial progenitor cell capability, and elevated the expression of the cell junction molecules to increase the vascularization of the spleen. This investigation found for the first time that the reestablishment of spleen vascularization restored spleen function by improving spleen immune cells and iron metabolism. These findings may be used as a strategy to minimize the side effects of anti-cancer drugs or to improve spleen vasculature-related diseases. IMPORTANCE Alginate oligosaccharide (AOS)-improved gut microbiota (A10-FMT) can rescue busulfan disrupted spleen vasculature. A10-FMT improved the cell proliferation rate, endothelial progenitor cell capability, and cell junction molecules to increase vasculature formation in the spleen. This reestablishment restored spleen function by improving spleen immune cells and iron metabolism. These findings are useful for the treatment of spleen vasculature-related diseases.

Pectin supplement alleviates gut injury potentially through improving gut microbiota community in piglets.

As pectin is widely used as a food and feed additive due to its tremendous prebiotic potentials for gut health. Yet, the underlying mechanisms associated with its protective effect remain unclear. Twenty-four piglets (Yorkshire × Landrace, 6.77 ± 0.92 kg) were randomly divided into three groups with eight replicates per treatment: (1) Control group (CON), (2) Lipopolysaccharide-challenged group (LPS), (3) Pectin-LPS group (PECL). Piglets were administrated with LPS or saline on d14 and 21 of the experiment. Piglets in each group were fed with corn-soybean meal diets containing 5% citrus pectin or 5% microcrystalline cellulose. Our result showed that pectin alleviated the morphological damage features by restoring the goblet numbers which the pig induced by LPS in the cecum. Besides, compared with the LPS group, pectin supplementation elevated the mRNA expression of tight junction protein [Claudin-1, Claudin-4, and zonula occludens-1 (ZO-1)], mucin (Muc-2), and anti-inflammatory cytokines [interleukin 10 (IL-10), and IL-22]. Whereas pectin downregulated the expression of proinflammatory cytokines (IL-1β, IL-6, IL-18), tumor necrosis factor-&alpha (TNF-α), and NF-κB. What is more, pectin supplementation also significantly increased the abundance of beneficial bacteria (Lactobacillus, Clostridium_sensu_stricto_1, Blautia, and Subdoligranulum), and significantly reduced the abundance of harmful bacteria, such as Streptococcus. Additionally, pectin restored the amount of short-chain fatty acids (SCFAs) after being decreased by LPS (mainly Acetic acid, Propionic acid, and Butyric acid) to alleviate gut injury and improve gut immunity via activating relative receptors (GPR43, GPR109, AhR). Mantel test and correlation analysis also revealed associations between intestinal microbiota and intestinal morphology, and intestinal inflammation in piglets. Taken together, dietary pectin supplementation enhances the gut barrier and improves immunity to ameliorate LPS-induced injury by optimizing gut microbiota and their metabolites.

Tremella fuciformis polysaccharide reduces obesity in high-fat diet-fed mice by modulation of gut microbiota.

Obesity is a metabolic disease associated with gut microbiota and low-grade chronic inflammation. Tremella fuciformis is a medicinal and edible fungus; polysaccharide (TP) is the main active component, which has a variety of biological activities, such as hypoglycemic and hypolipidemic. However, the anti-obesity effects and potential mechanisms of TP have never been reported. This study was conducted to elucidate the inhibitory effect of TP on high-fat diet (HFD)-induced obesity in mice. Mice were split into five groups: normal chow diet (NCD) group, NCD_TP_H group, HFD group, HFD_TP_L group and HFD_TP_H group. Our study showed that TP inhibited high-fat diet-induced weight gain and fat accumulation in mice and reduced blood glucose, hyperlipidemia and inflammation. TP also improved gut microbiota disorders by reducing the Firmicutes/Bacteroidetes ratio and modulating the relative abundance of specific gut microbiota. We also found that the anti-obesity and gut microbiota-modulating effects of TP could be transferred to HFD-fed mice via faecal microbiota transplantation (FMT), confirming that the gut microbiota was one of the targets of TP for obesity inhibition. Further studies showed that TP increased the production of short-chain fatty acids and the secretion of intestinal hormones. Our studies showed that TP inhibited obesity by modulating inflammation and the microbe-gut-brain axis, providing a rationale for developing TP to treat obesity and its complications.

Effect of molecular hydrogen treatment on Sepsis-Associated encephalopathy in mice based on gut microbiota.

In our experiments, male wild-type mice were randomly divided into four groups: the sham, SAE, SAE + 2% hydrogen gas inhalation (H2 ), and SAE + hydrogen-rich water (HW) groups. The feces of the mice were collected for 16 S rDNA analysis 24 h after the models were established, and the serum and brain tissue of the mice were collected for nontargeted metabolomics analysis. Destruction of the intestinal microbiota is a risk factor for sepsis and subsequent organ dysfunction, and up to 70% of severely ill patients with sepsis exhibit varying degrees of sepsis-associated encephalopathy (SAE). The pathogenesis of SAE remains unclear. We aimed to explore the changes in gut microbiota in SAE and the regulatory mechanism of molecular hydrogen. Molecular hydrogen treatment significantly improved the functional outcome of SAE and downregulated inflammatory reactions in both the brain and the gut. In addition, molecular hydrogen treatment improved gut microbiota dysbiosis and partially amended metabolic disorder after SAE. Molecular hydrogen treatment promotes functional outcomes after SAE in mice, which may be attributable to increasing beneficial bacteria, repressing harmful bacteria, and metabolic disorder, and reducing inflammation.

Dietary Catalase Supplementation Alleviates Deoxynivalenol-Induced Oxidative Stress and Gut Microbiota Dysbiosis in Broiler Chickens.

Catalase (CAT) can eliminate oxygen radicals, but it is unclear whether exogenous CAT can protect chickens against deoxynivalenol (DON)-induced oxidative stress. This study aimed to investigate the effects of supplemental CAT on antioxidant property and gut microbiota in DON-exposed broilers. A total of 144 one-day-old Lingnan yellow-feathered male broilers were randomly divided into three groups (six replicates/group): control, DON group, and DON + CAT (DONC) group. The control and DON group received a diet without and with DON contamination, respectively, while the DONC group received a DON-contaminated diet with 200 U/kg CAT added. Parameter analysis was performed on d 21. The results showed that DON-induced liver enlargement (p < 0.05) was blocked by CAT addition, which also normalized the increases (p < 0.05) in hepatic oxidative metabolites contents and caspase-9 expression. Additionally, CAT addition increased (p < 0.05) the jejunal CAT and GSH-Px activities coupled with T-AOC in DON-exposed broilers, as well as the normalized DON-induced reductions (p < 0.05) of jejunal villus height (VH) and its ratio for crypt depth. There was a difference (p < 0.05) in gut microbiota among groups. The DON group was enriched (p < 0.05) with some harmful bacteria (e.g., Proteobacteria, Gammaproteobacteria, Enterobacteriales, Enterobacteriaceae, and Escherichia/Shigella) that elicited negative correlations (p < 0.05) with jejunal CAT activity, and VH. DONC group was differentially enriched (p < 0.05) with certain beneficial bacteria (e.g., Acidobacteriota, Anaerofustis, and Anaerotruncus) that could benefit intestinal antioxidation and morphology. In conclusion, supplemental CAT alleviates DON-induced oxidative stress and intestinal damage in broilers, which can be associated with its ability to improve gut microbiota, aside from its direct oxygen radical-scavenging activity.

Zeaxanthin Dipalmitate-Enriched Emulsion Stabilized with Whey Protein Isolate-Gum Arabic Maillard Conjugate Improves Gut Microbiota and Inflammation of Colitis Mice.

In the present study, protein-polysaccharide Maillard conjugates were used as novel emulsifiers and bioactive carriers. Effects and potential mechanisms of zeaxanthin dipalmitate (ZD)-enriched emulsion stabilized with whey protein isolate (WPI)-gum Arabic (GA) conjugate (WPI-GA-ZD) and ZD-free emulsion (WPI-GA) on gut microbiota and inflammation were investigated using a model of dextran sulfate sodium (DSS)-induced colitis in mice. As a result, supplementation with WPI-GA and WPI-GA-ZD improved the serum physiological and biochemical indicators, decreased the expression of pro-inflammatory cytokines and related mRNA, as well as increased the tight junction proteins to a certain extent. 16S rDNA sequencing analyses showed that supplementation with WPI-GA and WPI-GA-ZD presented differential modulation of gut microbiota and played regulatory roles in different metabolic pathways to promote health. Compared with WPI-GA, the relative abundances of Akkermansia, Lactobacillus and Clostridium_IV genera were enriched by the intervention of WPI-GA-ZD. Overall, the designed carotenoid-enriched emulsion stabilized with protein-polysaccharide conjugates showed potential roles in promoting health.

Washed microbiota transplantation improves patients with metabolic syndrome in South China.

Metabolic syndrome (MS) is a growing public health problem worldwide. The clinical impact of fecal microbiota transplantation (FMT) from healthy donors in MS patients is unclear, especially in southern Chinese populations. This study aimed to investigate the effect of washed microbiota transplantation (WMT) in MS patients in southern China. The clinical data of patients with different indications receiving 1-3 courses of WMT were retrospectively collected. The changes of BMI, blood glucose, blood lipids, blood pressure and other indicators before and after WMT were compared, such as fasting blood glucose (FBG), glycated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c)), high-density lipoprotein cholesterol (HDL-c), non-high-density lipoprotein (non-HDL-c), systolic blood pressure (SBP), diastolic blood pressure (DBP), etc. At the same time, comprehensive efficacy evaluation and atherosclerotic cardiovascular disease (ASCVD) grade assessment were performed on MS patients. Finally, 16S rRNA gene amplicon sequencing was performed on fecal samples of MS patients before and after transplantation. A total of 237 patients were included, including 42 in the MS group and 195 in the non-MS group. For MS patients, WMT significantly improved the comprehensive efficacy of MS in short term 40.48% (p<0.001), medium term 36.00% (p=0.003), and long term 46.15% (p=0.020). Short-term significantly reduced FBG (p=0.023), TG (p=0.030), SBP (p=0.026) and BMI (p=0.031), and increased HDL-c (p=0.036). The medium term had a significant reduction in FBG (p=0.048), TC (p=0.022), LDL-c (p=0.043), non-HDL-c (p=0.024) and BMI (p=0.048). WMT had a significant short term (p=0.029) and medium term (p=0.011) ASCVD downgrading effect in the high-risk group of MS patients. WMT improved gut microbiota in MS patients. WMT had a significant improvement effect on MS patients and a significant downgrade effect on ASCVD risk in the high-risk group of patients with MS. WMT could restore gut microbiota homeostasis in MS patients. Therefore, the regulation of gut microbiota by WMT may provide a new clinical approach for the treatment of MS.

Dietary supplementation of squalene increases the growth performance of early-weaned piglets by improving gut microbiota, intestinal barrier, and blood antioxidant capacity.

This study aimed to investigate the effects of dietary squalene (SQ) supplementation on the growth performance of early-weaned piglets. Twenty early-weaned piglets were randomly divided into two groups, the squalene group (SQ) and the control group (CON). The CON group was fed a basal diet, and the SQ group was fed a basal diet with 250 mg/kg squalene. The feeding period lasted 21 days. The results showed that SQ significantly increased the final body weight (FWB, P < 0.05), average daily gain (ADG, P < 0.05), and average daily feed intake (ADFI, P < 0.05) and significantly decreased the F/G ratio (feed intake/gain, P < 0.05) and diarrhea index (DI, P < 0.05). In terms of blood biochemical indicators, SQ significantly increased anti-inflammatory factors such as transforming growth factor-β (TGF-β, P < 0.001), interleukin-10 (IL-10, P < 0.001), and interferon-γ (IFN-γ, P < 0.01), and decreased pro-inflammatory factors such as tumor necrosis factor-α (TFN-α, P < 0.001) and interleukin-6 (IL-6, P < 0.001). Furthermore, SQ significantly increased blood antioxidant indexes (P < 0.001) such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and total antioxidant capacity (T-AOC) and significantly decreased the level of malondialdehyde (MDA) (P < 0.001). The villus height (P < 0.001) and V/C ratio (villus height/crypt depth, P < 0.001) of the jejunum were significantly increased in the SQ group, while the crypt depth (P < 0.01) was decreased compared to the CON group. The intestinal permeability indexes, namely diamine oxidase (DAO), D-lactic acid (D-Lac), regenerative insulin-derived protein 3 (REG-3), and FITC-Dextran 4 (FD4), significantly decreased the concentrations in the treatment group (P < 0.001), and the antioxidant indexes of the jejunum, such as SOD, GSH-Px, CAT, and MDA, were improved by adding SQ. The qPCR results showed that adding SQ could significantly increase the mRNA expression of jejunal tight-junction proteins, such as zonula occludens-1 (ZO-1, P < 0.001), Occludin (P < 0.001), Claudin (P < 0.001), glucagon-like peptide-2 (GLP-2, P < 0.001), and insulin-like growth factor-1 (IGF-1, P < 0.001). Then, we used Western blotting experiments to further confirm the qPCR results. In addition, it was found that adding SQ increased the abundance of beneficial bacteria such as Gemmiger (P < 0.01) and decreased the abundance of harmful bacteria such as Alloprevotella (P < 0.05), Desulfovibrio (P < 0.05), and Barnesiella (P < 0.05). It was interesting that there was a very close correlation among the fecal microbes, growth performance parameters, intestinal barrier, and blood biochemical indicators. In conclusion, the data suggest that SQ supplementation could effectively improve the growth performance of early-weaned piglets by improving the gut microbiota, intestinal barrier, and antioxidant capacity of the blood and jejunal mucosa.

Effects of sweeteners on host physiology by intestinal mucosal microbiota: Example-addition sweeteners in Qiweibaizhu Powder on intestinal mucosal microbiota of mice with antibiotic-associated diarrhea.

In recent years, sweeteners have gained massive popularity under the trend of limiting sugar intake. Our previous study found that Qiweibaizhu Powder (QWBZP) could improve gut microbiota dysbiosis and has good efficacy in treating antibiotic-associated diarrhea (AAD). In this study, we investigated the effects of sucrose, sorbitol, xylitol, and saccharin on the intestinal mucosal microbiota of AAD mice treated with QWBZP. When the AAD model was constructed by being gavaged mixed antibiotic solution, Kunming mice were randomly assigned to seven groups: the control (mn) group, the ADD (mm) group, the QWBZP (mq) group, the saccharin + QWBZP (mc) group, the sucrose + QWBZP (ms) group, the xylito + QWBZP (mx) group, and the sorbitol + QWBZP (msl) group. Subsequently, 16S rRNA gene amplicon sequencing was used to analyze the intestinal mucosal microbiota composition and abundance. The results showed that feces from AAD mice were diluted and wet and improved diarrhea symptoms with QWBZP and sorbitol. In contrast, the addition of sucrose, saccharin, and xylitol delayed the healing of diarrhea. The relative abundance of intestinal mucosal microbiota showed Glutamicibacter, Robinsoniella, and Blautia were characteristic bacteria of the mx group, Candidatus Arthromitus, and Bacteroidales_S24-7_group as the typical bacteria of the mn group, Clostridium_innocuum_group as the distinct bacteria of the mm group. Mycoplasma and Bifidobacterium as the characteristic bacteria of the ms group. Correlation analysis of typical bacterial genera with metabolic functions shows that Blautia negatively correlates with D-Glutamine and D-glutamate metabolism. Bacteroidales_S24-7_group has a significant negative correlation with the Synthesis and degradation of ketone bodies. The study confirmed that sucrose, sorbitol, xylitol, and saccharin might further influence metabolic function by altering the intestinal mucosal microbiota. Compared to the other sweetener, adding sorbitol to QWBZP was the best therapeutic effect for AAD and increased the biosynthesis and degradation activities. It provides the experimental basis for applying artificial sweeteners in traditional Chinese medicine (TCM) as a reference for further rational development and safe use of artificial sweeteners.

Qin-Qiao-Xiao-Du formula alleviate influenza virus infectious pneumonia through regulation gut microbiota and metabolomics

Qin-Qiao-Xiao-Du (QQXD), a traditional Chinese medicine (TCM) formula, has been used in the clinical treatment of influenza virus pneumonia. However, the effects and mechanisms of QQXD on influenza virus pneumonia remain unknown. Therefore, this study explores the mechanisms of QQXD in the treatment of influenza virus pneumonia from the point of view of intestinal flora and metabolism. The results showed that QQXD was able to reduce mortality, weight loss, lung viral load, lung index, and lung injury in influenza virus mice. A cytokine array found that the QQXD attenuated the expression of serum IL-1α, IL-4, IL-12(P70), and TNF-α. Subsequently, 16s rRNA gene sequencing showed that QQXD could increase the relative abundances of Gemmiger, Anaerofustis, Adlercreutzia, and Streptococcus and decrease those of Dehalobacteriu, Burkholderia, Prevotella, Butyrimimonas, Delftia, and others. Meanwhile, targeted metabolic profiling analysis showed that QQXD could regulate nitrogen metabolism, phenylalanine metabolism, valine, leucine, and isoleucine biosynthesis. Correlation analysis demonstrated that the regulatory effect of QQXD on the cyanoamino acid metabolism pathway was associated with changes in the abundance of Parabacteroides, Pediococcus, and Clostridium in influenza mice. In conclusion, our study revealed that QQXD can inhibit influenza virus replication, suppress cytokine storms, and protect mice from influenza virus infection pneumonia. The mechanisms are likely to be related to improved gut microbiota dysbiosis, increased intestinal carbohydrate metabolism, and up-regulated cyanoamino acid metabolism pathways.

Advances in the roles and mechanisms of lignans against Alzheimer's disease.

Background: Alzheimer’s disease (AD) is a serious neurodegenerative disease associated with the memory and cognitive impairment. The occurrence of AD is due to the accumulation of amyloid β-protein (Aβ) plaques and neurofibrillary tangles (NFTs) in the brain tissue as well as the hyperphosphorylation of Tau protein in neurons, doing harm to the human health and even leading people to death. The development of neuroprotective drugs with small side effects and good efficacy is focused by scientists all over the world. Natural drugs extracted from herbs or plants have become the preferred resources for new candidate drugs. Lignans were reported to effectively protect nerve cells and alleviate memory impairment, suggesting that they might be a prosperous class of compounds in treating AD. Objective: To explore the roles and mechanisms of lignans in the treatment of neurological diseases, providing proofs for the development of lignans as novel anti-AD drugs. Methods: Relevant literature was extracted and retrieved from the databases including China National Knowledge Infrastructure (CNKI), Elsevier, Science Direct, PubMed, SpringerLink, and Web of Science, taking lignan, anti-inflammatory, antioxidant, apoptosis, nerve regeneration, nerve protection as keywords. The functions and mechanisms of lignans against AD were summerized. Results: Lignans were found to have the effects of regulating vascular disorders, anti-infection, anti-inflammation, anti-oxidation, anti-apoptosis, antagonizing NMDA receptor, suppressing AChE activity, improving gut microbiota, so as to strengthening nerve protection. Among them, dibenzocyclooctene lignans were most widely reported and might be the most prosperous category in the develpment of anti-AD drugs. Conclusion: Lignans displayed versatile roles and mechanisms in preventing the progression of AD in in vitro and in vivo models, supplying potential candidates for the treatment of nerrodegenerative diseases.

Morinda officinalis Polysaccharides Ameliorates Bone Growth by Attenuating Oxidative Stress and Regulating the Gut Microbiota in Thiram-Induced Tibial Dyschondroplasia Chickens.

Tibial dyschondroplasia (TD) occurs in chickens and other fast-growing birds, affecting their cartilage growth and leading to reduced meat quality in broilers. Morinda officinalis polysaccharide (MOP) is one of the chief active components of Morinda officinalis, which promotes bone formation, inhibiting bone loss and having anti-oxidant and anti-inflammatory properties. A total of 120 AA chickens were randomly divided into the CON group (basal diet), TD group (100 mg/kg thiram + basal diet), and MOP group (100 mg/kg thiram + basal diet + water with 500 mg/kg MOP). The experiment lasted 21 days. The results showed that MOP could alleviates broiler lameness caused by TD, restore the morphological structure of tibial growth plate (TGP), increase tibial weight (p < 0.05), balance the disorder of calcium and phosphorus metabolism, and promote bone formation by increasing the expression of BMP-2, Smad4, and Runx2 genes In addition, MOP supplementation stimulated the secretion of plasma antioxidant enzymes (T-SOD and GSH-Px) by regulating the expression of SOD and GPX-1 genes, thereby enhancing the antioxidant capacity of TD broilers. Interestingly, we observed MOP can also improve gut microbiota by increasing the beneficial bacteria count and decreasing the harmful bacteria count. These findings indicated that MOP can regulate bone formation through the BMP/Smads signaling pathway, attenuating oxidative stress and regulating the gut microbiota of TD broilers, so as to achieve the effect of treating TD. This suggests that MOP might be a potential novel drug in the treatment of TD in chickens.

In vivo evidence of the prevents DSS-induced colitis of Lactiplantibacillus plantarum L15.

Ulcerative colitis (UC) is challenging to treat and severely impacts patients and families. A previous study reported immunomodulatory and reduction of pro-inflammatory properties for the Lactiplantibacillus plantarum L15. This study aimed to analyze the preventive properties and mechanistic actions in an in vivo colitis model. The histopathological alteration, inflammation cytokines, and intestinal barrier function were analyzed. Subsequently, the cecal gut microbiota contents and products from different groups were detected. Finally, gene expressions related to the NF-κB signaling process were evaluated. L. plantarum L15 significantly decreased disease activity index (DAI), myeloperoxidase activity (MPO), pro-inflammatory cytokine (TNF-α, IL-1β, and IL-6) level, and increased weight change, colon length, and production of inflammation-suppressing cytokines. Furthermore, this strain supplementation substantially increased ZO-1, Occludin, and Claudin-1, and MUC2 mRNA expression levels with a corresponding decrease in serum lipopolysaccharide and D-lactic acid contents. In addition, L. plantarum L15 improved gut microbiota composition and increased short-chain fatty acid (SCFAs) in the colon content, which significantly reduced the transfer of NF-κB p65 to the nucleus. Our findings provide a theoretical basis for L. plantarum L15 as a preventive candidate for UC.

Whey protein hydrolysates alleviated weight gain and improved muscle in middle-aged obese mice induced by a high-fat diet

Whey protein (WP) and whey protein hydrolysates (WPH) may have the potency to promote weight loss, preserve muscle and improve gut microbiota composition. The present study explored the effect of WPH vs WP on weight management in obese middle-aged mice in the content of changes in fat mass, muscle mass and gut microbiota composition. The present results showed that WPH significantly reduced energy intake, attenuated weight gain and improved blood lipids and glucose. Moreover, WPH reduced ectopic fat deposition and enhanced antioxidant capacity in muscle, but did not significantly affect muscle mass. WPH failed to reverse the microbial diversity reduction caused by a high-fat diet, but increased Akkermansia and Clostridium XVIII abundances and decreased Alistipes abundance. In conclusion, WPH is expected to have good prospects in weight management in middle age.

Brazilian green propolis improves gut microbiota dysbiosis and protects against sarcopenic obesity.

Brazilian green propolis is an important honeybee product that is considered beneficial for health. Here, we examined the therapeutic potential of dietary supplementation with propolis against sarcopenic obesity using Db/Db mice. Db/m mice fed a normal diet alone and Db/Db mice fed normal diet alone, or supplemented with different amounts of propolis (0.08, 0.4 and 2%), were examined for effects on sarcopenic obesity. Propolis improved the glucose tolerance (P<0.001), increased the grip strength (P<0.001) and the weight of soleus (P=0.006) and plantaris muscles (P=0.008). Moreover, propolis improved the non-alcoholic fatty liver disease activity score (P<0.001) and decreased the expression of genes related to inflammation, liver fibrosis and fatty acid metabolism. Propolis decreased the accumulation of saturated fatty acids in the liver and increased their excretion in faeces. With regard to the innate immunity, propolis decreased the ratio of M1 macrophages (P=0.008) and Type 1 and 3 innate lymphoid cells to CD45-positive cells (P<0.001) and increased the ratio of M2 macrophages (P=0.002) and ILC2s (P=0.007) in the liver. Additionally, propolis decreased the expression of genes related to muscle atrophy and inflammation and the concentration of saturated fatty acids in the soleus muscle. 16S rRNA phylogenetic sequencing revealed that propolis increased the Bacteroidetes/Firmicutes ratio, and the abundance of Butyricicoccus and Acetivibrio genera. Gut microbiota related to the pentose phosphatase pathway and glycerolipid metabolism was more prevalent after the administration of propolis. This is the first study to demonstrate that propolis can improve sarcopenic obesity by improving dysbiosis due to overeating and provides new insights into diet-microbiota interactions during sarcopenic obesity.

Gut microbiota profiling revealed the regulating effects of salidroside on iron metabolism in diabetic mice.

BackgroundDiabetes is a common metabolic disease that is associated with gut microbiota dysbiosis and iron metabolism. Salidroside (SAL) is the main ingredient of the traditional Chinese herb Rhodiola, previous studies have shown that SAL could reshape the gut microbiota and limit iron accumulation. Therefore, it is possible that SAL can act as an alternative therapy for diabetes, and its underlying mechanism is worth exploring.MethodsSAL was used to treat diabetic db/db mice. Serum glucose and iron levels and the histopathology of myocardial fibres were evaluated. The gut microbiota composition was determined by 16S rRNA Illumina sequencing technology.ResultsTreatment with SAL significantly reduced blood glucose and ameliorated diabetic cardiomyopathy in diabetic db/db mice, which was accompanied by inhibited ferroptosis and iron accumulation. Furthermore, the 16S rRNA sequencing results showed that SAL induced a change in the gut microbiota composition. Overall, SAL could increase the proportion of probiotic bacteria and decrease Lactobacillus to improve gut microbiota. Specifically, SAL increased the ratio of Bacteroidetes to Firmicutes in diabetic mice. The most significant biomarker was the genus Lactobacillus between the MD group and the SAL group. In addition, COG and KEGG analyses suggested that SAL mainly participated in nutrient metabolism, among them iron metabolism was associated with the abundance of Lactobacillus.ConclusionsSAL could reduce the glucose level and protect against diabetic cardiomyopathy in diabetic mice, which might be mediated by the change in the gut microbiota and the regulation of iron metabolism. The findings suggested that SAL was a promising complementary option for diabetes therapy.

Effects of Stocking Density on Fatty Acid Metabolism by Skeletal Muscle in Mice.

Simple SummaryAppropriate stocking density is one of the most basic guarantees for experimental animals, and it is also a prerequisite for ensuring the accuracy and credibility of experimental data science. Stocking density, which is related to gut microbiota, affects laboratory mouse health. The aim of this study is to evaluate whether the stocking density of experimental animals affects the gut microbiota, fatty acid metabolism, and muscle quality, and ultimately affects their welfare. According to our results, medium stocking density improves gut microbiota, fatty acid metabolism, and muscle quality in experimental animals.Specific pathogen-free (SPF) grade laboratory animals are kept in specific cages for life. The limited space could affect the characterization of colonization and dynamic changes related to gut microorganisms, and affect adipokines, even further affecting the fat synthesis and muscle quality of animals. The objective of this study was to analyze the stocking density on the dynamic distribution of gut microbiota, fat synthesis and muscle quality of SPF grade Kunming mice. Three housing densities were accomplished by raising different mice per cage with the same floor size. Kunming mice were reared at low stocking density (LSD, three mice a group), medium stocking density (MSD, 5 mice a group), and high stocking density (HSD, 10 mice a group) for 12 weeks. The results demonstrated that the stocking density affected intestinal microbial flora composition. We found that compared with the MSD group, the abundance of Lactobacillus in the LSD group and the HSD group decreased, but the abundance of unclassified_Porphyromonadaceae increased. Moreover, fat synthesis and muscle quality were linked to the intestinal microbial flora and stocking density. Compared with the LSD group and the HSD group, the MSD group had a more balanced gut flora, higher fat synthesis and higher muscle quality. Overall, this study demonstrated that stocking density could affect gut microbiota composition, and reasonable stocking density could improve fat synthesis and muscle quality. Our study will provide theoretical support for the suitable stocking density of laboratory animals.