Abundance Of Akkermansia Research Articles

Vancomycin Pretreatment on MPTP-Induced Parkinson's Disease Mice Exerts Neuroprotection by Suppressing Inflammation Both in Brain and Gut.

A growing body of evidence implies that gut microbiota was involved in pathogenesis of Parkinson's disease (PD), but the mechanism is still unclear. The aim of this study is to investigate the effects of antibiotics pretreatment on the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mice. In this study, vancomycin pretreatment was given by gavage once daily with either vancomycin or distilled water for 14days to mice, then mice were administered with MPTP (20mg/kg, i.p) for four times in one day to establish an acute PD model. Results show that vancomycin pretreatment significantly improved motor dysfunction of mice in pole and traction tests. Although vancomycinpretreatment had no effect on dopamine (DA) or the process of DA synthesis, it inhibited the metabolism of DA by suppressing the expression of striatal monoamine oxidase B (MAO-B). Furthermore, vancomycin pretreatment reduced the number of astrocytes and microglial cells in the substantia nigra pars compacta (SNpc) to alleviate neuroinflammation, decreased the expression of TLR4/MyD88/NF-κB/TNF-α signaling pathway in both brain and gut. Meanwhile, vancomycin pretreatment changed gut microbiome composition and the levels of fecal short chain fatty acids (SCFAs). The abundance of Akkermansia and Blautia increased significantly after vancomycin pretreatment, which might be related to inflammation and inhibition of TLR4 signaling pathway. In summary, these results demonstrate that the variation of gut microbiota and its metabolites induced by vancomycin pretreatment might decrease dopamine metabolic rate and relieve inflammation in both gut and brain via the microbiota-gut-brain axis in MPTP-induced PD mice. The neuroprotection of vancomycin pretreatment on MPTP-induced Parkinson's disease mice The alterations of gut microbiota and SCFAs induced by vancomycin pretreatment might not only improve motor dysfunction, but also decrease dopamine metabolism and relieve inflammation in both brain and gut via TLR4/MyD88/NF-κB/TNF-α pathway in MPTP-induced PD mice.

Gut microbiota mediates the alleviative effect of polar lipids-enriched milk fat globule membrane on obesity-induced glucose metabolism disorders in peripheral tissues in rat dams.

Obesity during pregnancy and lactation not only increases the incidence of metabolic disorders and gestational diabetes in mothers, but also programs adiposity and related metabolic diseases in offspring. The aim of this study was to investigate the effects of milk polar lipids on gut microbiota and glucose metabolism in high-fat diet (HFD)-fed rat dams. Sprague Dawley (SD) female rats were fed a HFD for 8 weeks to induce obesity, followed by HFD with or without oral administration of polar lipids-enriched milk fat globule membrane (MFGM-PL) at 400 mg/kg BW during pregnancy and lactation. At the end of lactation, fresh fecal samples of dams were collected, the gut microbiota was assessed, and the insulin-signaling protein expression in peripheral tissues (adipose tissue, liver and skeletal muscle) were measured. MFGM-PL supplementation attenuated body weight gain, ameliorated serum lipid profiles and improved insulin sensitivity in obese dams at the end of lactation. 16 S rDNA sequencing revealed that MFGM-PL increased the community richness and diversity of gut microbiota. The composition of gut microbiota was also changed after MFGM-PL supplementation as shown by an increase in the ratio of Bacteroidetes/Firmicutes and the relative abundance of Akkermansia, as well as a decrease in the relative abundance of Ruminococcaceae. The functional prediction of microbial communities by PICRUSt analysis showed that there were 7 KEGG pathways related to carbohydrate metabolism changed after MFGM-PL supplementation to HFD dams, including glycolysis/gluconeogenesis and insulin signaling pathway. Furthermore, MFGM-PL improved insulin signaling in the peripheral tissues including liver, adipose tissue and skeletal muscle. MFGM-PL supplementation during pregnancy and lactation improves the glucose metabolism disorders in HFD-induced obese dams, which may be linked to the regulation of gut microbiota induced by MFGM-PL.

Orange Pectin with Compact Conformation Effectively Alleviates Acute Colitis in Mice.

A comprehensive understanding of the relationships between the structure and function is critical for the targeted preparation of functional pectins. In this study, we compared the alleviating effects of five orange pectins (200 mg/kg) extracted using acid (P2), alkali (P10), cellulase (C), acid + cellulase (P2 + C), and alkali + cellulase (P10 + C) on dextran sodium sulfate-induced acute colitis. The physiological and histopathological indicators revealed that the alleviating effects were most significant for P10 + C, followed by P10, P2 + C, P2, and C. P10 + C increased the diversity and relative abundance of Akkermansia, leading to increased generation of colonic short-chain fatty acids as well as mRNA and protein expressions of GPR43, GPR109A, claudin-1, ZO-1, and occludin. Therefore, proinflammatory cytokines were decreased, and anti-inflammatory cytokines were increased. A compact conformation of P10 + C contributed to the alleviation effects on acute colitis. Alkali + cellulase-extracted orange pectin with a compact conformation has potential as adjuvant treatment for intestinal inflammation.

Effect of 1-Deoxynojirimycin on insulin resistance in prediabetic mice based on next-generation sequencing and intestinal microbiota study

Ethnopharmacological relevance1-Deoxynojirimycin (DNJ), the major alkaloid in Morus alba L., is the main effective constituent in “Mulberry twig Alkaloids Tablets” launched in China in 2020. Prediabetes, characterized by insulin resistance, is regarded as the key period for reversing Type 2 diabetes mellitus (T2DM) through lifestyle intervention and glucose-lowering drugs. Besides the excellent activity as an α-glucosidase inhibitor, DNJ also improves insulin sensitivity in T2DM murine models, yet the mechanism is still unclear. Besides, the pharmaceutical effect of DNJ on prediabetes is also undocumented. Aim of the studyThe aim of this study was to investigate the pharmaceutical effect of DNJ on high-fat and streptozotocin (STZ)-induced prediabetes mice, and to elucidate the mechanism of insulin resistance ameliorated by DNJ. Materials and methodsOral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed to detect blood glucose level and insulin sensitivity in mice. The levels of circulating lipopolysaccharide (LPS), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) in the plasma of mice were measured by limulus reagent and enzyme-linked immunosorbent assay (ELISA), respectively. Next-generation sequencing (NGS) and intestinal microbiota sequencing were used to screen the alterations in the transcriptome of liver tissues and to assess the differences in intestinal flora composition, respectively. Expression of cytokine signaling pathway inhibitor 3 (SOCS3), insulin receptor substrate (IRS1), p-IRS1 (Tyr896), occludin, and toll like receptor 4 (TLR4)/NF-κB signaling pathway were confirmed by western blotting. ResultsOur study revealed that DNJ decreased the blood glucose level and improve insulin sensitivity in prediabetic mice. DNJ significantly reduced the relative risk of T2DM in prediabetic mice by approximately 83.7%. Mechanistically, DNJ treatment suppressed the circulating levels of LPS, IL-6, and TNF-α in plasma and decreased the inflammatory infiltration in liver and colon tissues. DNJ-treatment increased the abundance of Akkermansia, Bifidobacterium, and Lactobacillus, and decreased the abundance of Enterococcaceae and Lachnospiraceae. Moreover, DNJ suppressed the expression of SOCS3 and the activity of TLR4/NF-κB signaling pathway, meanwhile improving the expression of occludin and the ratio of p-IRS1 (Tyr896)/IRS1. ConclusionsDNJ effectively ameliorates glucose and lipid metabolism in prediabetic mice, and decreased the relative risk of progression into T2DM from prediabetes. The suppressed immune responses play essential roles in the improvement of insulin resistance by DNJ treatment. In conclusion, DNJ from Morus alba L. is a promising alternative agent in T2DM prevention.

Amlodipine, an anti-hypertensive drug, alleviates non-alcoholic fatty liver disease by modulating gut microbiota.

Non-alcoholic fatty liver disease (NAFLD) represents a severe public health problem. It often coexists with hypertension in the context of metabolic syndrome. We investigated the effects of amlodipine on NAFLD combined with hypertension and investigated the underlying mechanism/s. Mice were fed with high-fat diet (HFD) and 0.05% N-nitro-L-arginine methylester sterile water to induce NAFLD with hypertension. Gut microbiota composition and function were assessed by 16S ribosomal DNA and metagenomic sequencing. Untargeted metabolome profiles were applied to identify differential metabolites in mice caecum. Amlodipine besylate and amlodipine aspartate significantly decreased liver injury and hepatic steatosis, and improved lipid metabolism with a concomitant reduction in the expression of lipogenic genes in mice with NAFLD and hypertension. Mechanistically, amlodipine besylate and amlodipine aspartate have potential to restore intestinal barrier integrity and improve antimicrobial defence, along with the elevated abundances of Akkermansia, Bacteroides and Lactobacillus. Noteworthily, the gut microbiota in amlodipine besylate- and amlodipine aspartate-treated mice had higher abundance of functional genes involved in taurine and hypotaurine metabolism. Consistently, the strengthened taurine and hypotaurine metabolism was confirmed by untargeted metabolome analysis. Based on the correlation and causal analysis, the altered gut microbiota composition and the enhancement of taurine and hypotaurine metabolism may synergistically decreased alanine aminotransferase, liver triglycerides, lipogenic genes and plasma cholesterol in HFD-fed hypertensive mice. Amlodipine besylate and amlodipine aspartate exert multifactorial improvements in NAFLD and hypertension by modulating gut microbiota. They may serve as promising therapeutic agents for treating these diseases.

The association of weight loss with changes in the gut microbiota diversity, composition, and intestinal permeability: a systematic review and meta-analysis

ABSTRACT The gut microbiome may be a mediator between obesity and health outcomes. However, it is unclear how intentional weight loss changes the gut microbiota and intestinal permeability. We aimed to systematically review and quantify this association. We searched Medline, Embase, CINAHL, Cochrane databases, and trial registries until June 2020 (PROSPERO: CRD42020205292). We included trials of weight loss interventions (energy-restricted diets, pharmacotherapy, bariatric surgery) reporting on the microbiome. Two reviewers independently completed screening, extraction, and risk assessment with the ROBINS-I tool. Pooled standardized mean differences (SMDs) were obtained from random-effects meta-analyses. Forty-seven trials with 1,916 participants (81% female) and a median follow-up of 6 months (range: 2–24) were included. Based on imprecise evidence but with fairly consistent direction of effect, weight loss was associated with a statistically significant increase in α-diversity [SMD: 0.4 (95% CI: 0.2, 0.6], p < .0001, I2 = 70%, n = 30 studies) and a statistically significant reduction in intestinal permeability [SMD: −0.7 (95% CI: −0.9, −0.4), p < .0001, I2 = 83%, n = 17 studies]. Each kg of weight loss was associated with a 0.012 (95% CI: 0.0003, 0.024, p = .045) increase in α-diversity and a −0.017 (95% CI: −0.034, −0.001, p = .038) reduction in intestinal permeability. There was clear evidence of increases in the relative abundance of Akkermansia, but no clear evidence of changes in individual phyla, species, or fecal short-chain fatty acids. Restricting the analyses to the studies with lower risk of bias did not materially alter the estimates. Increasing weight loss is positively associated with increases in gut microbiota α-diversity and reductions in intestinal permeability.

Dietary fiber modulates abdominal fat deposition associated with cecal microbiota and metabolites in yellow chickens

Excessive deposition of abdominal fat is a public concern in the yellow chicken industry related to human nutrition. The common practice of nutritionists is to increase the fiber content in feed to control abdominal fat deposition of chickens. Corncob meal (CCM) is the cheapest ingredient widely used in animal diets. The possible effects of CCM on chicken abdominal fat deposition and the possible mechanism involving cecal microbiota remain unknown. The objectives of this study were to investigate the effects of CCM in modulating abdominal fat deposition and the role of the cecal microbiota and their metabolites. A total of 200 ninety-day-old Huxu female chickens were divided into 2 dietary treatments, each with 10 replicates of 10 birds, and were fed two finisher diets, from 90 to 135 d. The diets were a typical corn-soybean control diet (CON) and that diet with CCM partially replacing corn and corn gluten meal. Results showed that the CCM diet markedly decreased live weight and abdominal fat percentage (P < 0.05); chickens fed the CCM diet exhibited lower (P < 0.01) expression in abdominal fat of fatty acid binding protein 4 (FABP4), stearoyl-CoA desaturase (SCD), fatty acid synthase (FAS), and peroxisome proliferator-activated receptor γ (PPARγ) but higher (P < 0.05) expression of estrogen receptor alpha (ESR1). The CCM increased the abundance of Akkermansia (P < 0.05) and markedly reduced the relative cecal abundance of Phascolarctobacterium (P < 0.01), Rikenellaceae (P < 0.05), and Faecalibacterium (P < 0.01). The metabolomic and biochemical analyses demonstrated that the CCM diet increased (P < 0.05) the concentrations of butyrate in cecal contents. The majority of the metabolites in cecal digesta with differences in abundance were organic acids. The CCM diet increased (P < 0.05) contents of (R)-5-diphosphomevalote, pantothenic acid, 2-epi-5-epi-valiolone 7-phosphate, D-ribose 5-diphosphate, arbutin 6-phosphate, D-ribitol 5-phosphate, undecanoic acid, nicotinic acid, 4-methyl-2-oxovaleric acid, while decreasing (P < 0.05) those of oleic acid, glutaric acid, adipic acid, suberic acid, and L-fuculose 1-phosphate. In conclusion, these findings demonstrated that the dietary CCM treatment significantly decreased abdominal fat and altered the cecal microbiota and metabolite profiles of the yellow chickens.

Sub-Chronic Difenoconazole Exposure Induced Gut Microbiota Dysbiosis in Mice.

Difenoconazole (DIF) is a widely separated triazole fungicide in many countries. The excessive usage of DIF increases the high volume of residues in agriculture production and water bodies. Some previous studies demonstrated the toxic effects of DIF on non-target animals, however, there were still some gaps in the knowledge of the potential hazards of DIF to mammals and human health. Herein, 7-week-old male mice were exposed to 30 and 100 mg/kg/day DIF for 14 and 56 days. We observed that 56 days of DIF exposure decreased the colonic mucus expression of alcin blue-periodic acid-schiff (AB-PAS) stain and the immunochemical stain of muc2 protein. The transcript levels of mucin protein (muc1, muc2 and muc3) decreased significantly in the gut of mice followed 56 days of 100 mg/kg/day DIF exposure. In addition, the gut microbiota composition was also affected after 14 or 56 days of DIF exposure. Although the mucus expression after 14 days of DIF exposure only decreased slightly, the gut microbiota composition compared with the control group was changed significantly. Moreover, the DIF-30 and DIF-100 caused respectively different changes on the gut microbiota. The relative abundance of Bacteroidetes decreased significantly after 14 days and 56 days of DIF exposure. After 14 days of DIF exposure, there were 35 and 18 differential genera in the DIF-30 and DIF-100 group, respectively. There were 25 and 32 differential genera in the DIF-30 and DIF-100 group after 56 days of exposure, respectively. Meanwhile, the alpha diversity indexes, including observed species, Shannon, Simpson, Chao1 and ACE, in gut microbiota decreased significantly after 56 days of DIF exposure. Interestingly, the relative abundance of Akkermansia increased significantly after 56 days of 100 mg/kg/d DIF exposure. Although Akkermansia was considered as one probiotic, the phenomenon of dramatic Akkermansia increase with the decrease in gut microbiota diversity needed further discussion. These results provided some new insights on how DIF exposure impacts the mucus barrier and induces gut microbiota dysbiosis.

Supplementing Mannan Oligosaccharide Reduces the Passive Transfer of Immunoglobulin G and Improves Antioxidative Capacity, Immunity, and Intestinal Microbiota in Neonatal Goats.

Successful establishment of passive immunity (PIT) and regulation of intestinal microbiota are crucial for ruminants to maintain body health and reduce the risk of disease during the neonatal period. Thus, the objective of this study was to investigate the effects of mannan oligosaccharide (MOS) supplementation on passive transfer of immunoglobulin G (IgG), serum inflammatory cytokines and antioxidant levels as well as bacteria composition in the ileal digesta. A total of 14 healthy neonatal Ganxi black goats with similar birth weight (BW: 2.35 ± 0.55 kg) were selected and allocated into two groups, only fed colostrum and milk replacer (CON, n = 7) and supplemented MOS (0.06% of birth BW) in the colostrum and milk replacer (MOS, n = 7). The results indicated that MOS supplementation significantly reduced (p < 0.05) serum IgG level at 3 and 6 h after colostrum feeding. Serum GLP-1 level of goats in the MOS group was significantly lower (p = 0.001) than that in the CON group. Goats in the MOS group had higher serum CAT and lower MDA level than those in the CON group (p < 0.05). Serum anti-inflammatory cytokine level of interleukin 4 (IL-4) was increased (p < 0.05), while pro-inflammatory cytokine IL-6 level was reduced (p < 0.05) in the MOS group when compared with the CON group. In addition, MOS supplementation remarkably increased (p < 0.05) the level of secretory IgA (sIgA) in the ileal digesta. Principal coordinate analysis of 16S rRNA sequence based on Brinary jaccard, Bray curtis, and weighted UniFrac distance of ileal microbiota showed a distinct microbial differentiation between the CON and MOS groups (p < 0.05). The relative abundance of Firmicutes in the MOS group was higher than that in the CON group, while the abundance of Verrucomicrobia was lower in the MOS group than that in the CON group at the phylum level (p < 0.05). The relative abundance of Proteobacteria tended to decrease (p = 0.078) in the MOS group at the phylum level. The results of LEfSe analysis showed that MOS group was characterized by a higher relative abundance of Lactobacillus, while the CON group was represented by a higher relative abundance of Akkermansia and Ruminiclostridium_5. Our findings demonstrated that MOS supplementation during the neonatal period increases antioxidant capacity and reduces the inflammatory response, and promotes IgA secretion and Lactobacillus colonization in the ileum. Thus, MOS induced positive effects are more pronounced in neonatal goats that might be an effective approach to maintain intestinal health and improve the surviving rate of neonatal ruminants.

Lactobacillus kefiranofaciens ZW18 from Kefir enhances the anti-tumor effect of anti-programmed cell death 1 (PD-1) immunotherapy by modulating the gut microbiota.

Research on probiotics assisting PD-1 inhibitors in anti-tumor therapy has attracted widespread attention. Therefore, it is important to find new probiotic strains with a PD-1 inhibitor promoting effect. This study aims to find a strain with a good promoting effect on PD-1 inhibitor treatment from 5 probiotic strains with the function of modulating the gut microbiota or enhancing immunity. A preclinical study on the effect of probiotics combined with PD-1 inhibitors in murine melanoma was designed. In this study, Lactobacillus kefiranofaciens ZW18 (ZW18) was found to have the best anti-melanoma effect among the probiotic candidates in PD-1 inhibitor treatment. ZW18 inhibited the tumor growth in PD-1-treated mice with an inhibition rate of 66.16% by activating the body's immunity and promoting the tumor CD8+ T cell infiltration. Moreover, the supplement of ZW18 optimized the composition of the gut microbiota in mice treated with PD-1 inhibitors, and significantly increased the abundance of Akkermansia, the Prevotellaceae_NK3B31_group and Muribaculum. Collectively, ZW18 could be regarded as a potential candidate strain for promoting tumor immunotherapy. ZW18 combined with PD-1 inhibitors has a possibility of serving as a functional food to assist tumor immunotherapy.

Bifidobacterium longum relieves constipation by regulating the intestinal barrier of mice.

Constipation is a major health concern worldwide, requiring effective and safe treatment options. This study mainly focused on three species and nine strains of bifidobacteria from different sources to study their abilities to relieve constipation induced by loperamide in BALB/C mice. By monitoring constipation-related indicators, it was found that only Bifidobacterium longum (B. longum) relieved constipation, which indicated that bifidobacteria had inter-species differences in relieving constipation. Furthermore, through the detection of biological, chemical, mechanical, and immune barriers in mice, it was discovered that B. longum upregulates the relative abundance of 22 genera that were positively related to faecal water content, small intestinal propulsion rate, acetate, propionate, and intestinal mechanical barrier and negatively correlated with inflammatory factors, AQP8 and the time of first black stool and downregulates the relative abundance of Akkermansia. Furthermore, it increased the level of acetate in faeces and reduced the expression of AQP8 in the colon. This enhances intestinal motility and improves water and electrolyte metabolism. Meanwhile, it inhibited inflammation and prevented loperamide-induced intestinal barrier damage in constipated mice by upregulating occludin and downregulating IL-1β and TNF-α. In summary, B. longum relieved constipation by regulating the intestinal barrier in constipated mice.

Apple Polyphenols Extracts Ameliorate High Carbohydrate Diet-Induced Body Weight Gain by Regulating the Gut Microbiota and Appetite.

To investigate the potential contribution of appetite regulation and modulation of gut microbiota to the ameliorated effects of apple polyphenols extracts (APE) on high carbohydrate diet (HCD)-induced body weight (BW) gain, we conducted this study. One hundred C57BL/6 male mice were randomly divided into seven groups and fed with the following diets for 12 weeks: chow diet (CON), HCD (HCD), high fructose and sucrose diet (HSCD), and HCD and HSCD with 125 or 500 mg/kg·day APE gavage. Compared to the CON group, the BW of mice in the HCD and HSCD groups increased significantly. HSCD induced a more significant weight gain in the white adipose tissue (WAT) and liver than HCD, accompanied by severe impairment of glucose tolerance and a larger diameter of adipocytes. On the other hand, by decreasing food intake, APE significantly reduced BW via mechanisms, including decreased weights of the WAT and liver, amelioration of glucose tolerance, and amplification of WAT browning by upregulating the mRNA levels of Ucp-1 and Cidea. Moreover, APE promoted transcription and secretion of GLP-1, with the increased expression of gut anorexigenic hormone peptides Ffar 2/3 in the colon and anorectic neuropeptide gene expression of Pomc, Cart, and Mc4r in the hypothalamus, causing increased satiety. Additionally, APE significantly increased Verrucomicrobia colonization and the relative abundance of Akkermansia. APE potentially ameliorates high simple carbohydrate diet-induced body weight gain by mechanisms related to gut microbiota regulation and appetite inhibition.

The Nutritional Supplement L-Alpha Glycerylphosphorylcholine Promotes Atherosclerosis.

L-alpha glycerylphosphorylcholine (GPC), a nutritional supplement, has been demonstrated to improve neurological function. However, a new study suggests that GPC supplementation increases incident stroke risk thus its potential adverse effects warrant further investigation. Here we show that GPC promotes atherosclerosis in hyperlipidemic Apoe−/− mice. GPC can be metabolized to trimethylamine N-oxide, a pro-atherogenic agent, suggesting a potential molecular mechanism underlying the observed atherosclerosis progression. GPC supplementation shifted the gut microbial community structure, characterized by increased abundance of Parabacteroides, Ruminococcus, and Bacteroides and decreased abundance of Akkermansia, Lactobacillus, and Roseburia, as determined by 16S rRNA gene sequencing. These data are consistent with a reduction in fecal and cecal short chain fatty acids in GPC-fed mice. Additionally, we found that GPC supplementation led to an increased relative abundance of choline trimethylamine lyase (cutC)-encoding bacteria via qPCR. Interrogation of host inflammatory signaling showed that GPC supplementation increased expression of the proinflammatory effectors CXCL13 and TIMP-1 and activated NF-κB and MAPK signaling pathways in human coronary artery endothelial cells. Finally, targeted and untargeted metabolomic analysis of murine plasma revealed additional metabolites associated with GPC supplementation and atherosclerosis. In summary, our results show GPC promotes atherosclerosis through multiple mechanisms and that caution should be applied when using GPC as a nutritional supplement.

Metronidazole and ciprofloxacin differentially affect chronic unpredictable mild stress-induced changes in the colon, cecum and ileum microbiota.

Antibiotics have been shown to have a major impact on the composition and metabolism of gut microbiota, while unpredictable stress has been shown to have major influences on gut microbiota homeostasis. However, the impact of combination antibiotics (e.g. metronidazole and ciprofloxacin) on gut microbiota dysbiosis that is induced by stress remains unclear. Here, chronic unpredictable mild stress (CUMS) was used to simulate unpredictable stress, and Sprague-Dawley rats received antibiotics (metronidazole and ciprofloxacin) after CUMS. The weights and coefficients of the thymus, liver and spleen were analysed. 16S rRNA gene sequencing was performed to determine the gut microbiota in the colon, cecum and ileum. We found that antibiotics decreased the CUMS-induced increases in spleen coefficients. Short-term antibiotic exposure significantly increased the cecum and ileum microbiota richness and significantly increased the ileum microbiota diversity after CUMS. Long-term antibiotic exposure significantly decreased the colon microbiota diversity and significantly increased the ileum microbiota richness after CUMS. The impacts of antibiotic exposure on the microbiota compositions at the phylum and genus levels in different gut segments were different after CUMS. However, it is worth noting that the most differentially abundant bacteria in the colon, cecum and ileum were all Verrucomicrobia under long-term antibiotic exposure. Antibiotic exposure significantly increased the relative abundance of Lactobacillus in the colon and ileum and significantly increased the relative abundance of Akkermansia in the colon and cecum after CUMS. In conclusion, this study showed that metronidazole and ciprofloxacin differentially affected the CUMS-induced changes in the microbiota of the colon, cecum and ileum.Key points• The impacts of antibiotic exposure on the changes in microbiota that were induced by chronic unpredictable mild stress were analysed.• We collected rat gut microorganisms from the colon, cecum and ileum.• The diversities, compositions, functions and network structures were analysed.

Changes in Gut Bacterial Translation Occur before Symptom Onset and Dysbiosis in Dextran Sodium Sulfate-Induced Murine Colitis.

ABSTRACTLongitudinal studies on the gut microbiome that follow the effect of a perturbation are critical in understanding the microbiome’s response and succession to disease. Here, we use a dextran sodium sulfate (DSS) mouse model of colitis as a tractable perturbation to study how gut bacteria change their physiology over the course of a perturbation. Using single-cell methods such as flow cytometry, bioorthogonal noncanonical amino acid tagging (BONCAT), and population-based cell sorting combined with 16S rRNA sequencing, we determine the diversity of physiologically distinct fractions of the gut microbiota and how they respond to a controlled perturbation. The physiological markers of bacterial activity studied here include relative nucleic acid content, membrane damage, and protein production. There is a distinct and reproducible succession in bacterial physiology, with an increase in bacteria with membrane damage and diversity changes in the translationally active fraction, both, critically, occurring before symptom onset. Large increases in the relative abundance of Akkermansia were seen in all physiological fractions, most notably in the translationally active bacteria. Performing these analyses within a detailed, longitudinal framework determines which bacteria change their physiology early on, focusing therapeutic efforts in the future to predict or even mitigate relapse in diseases like inflammatory bowel diseases.IMPORTANCE Most studies on the gut microbiome focus on the composition of this community and how it changes in disease. However, how the community transitions from a healthy state to one associated with disease is currently unknown. Additionally, common diversity metrics do not provide functional information on bacterial activity. We begin to address these two unknowns by following bacterial activity over the course of disease progression, using a tractable mouse model of colitis. We find reproducible changes in gut bacterial physiology that occur before symptom onset, with increases in the proportion of bacteria with membrane damage, and changes in community composition of the translationally active bacteria. Our data provide a framework to identify possible windows of intervention and which bacteria to target in microbiome-based therapeutics.

Ageing and rejuvenation models reveal changes in key microbial communities associated with healthy ageing

BackgroundThe gut microbiota is associated with diverse age-related disorders. Several rejuvenation methods, such as probiotic administration and faecal microbiota transplantation, have been applied to alter the gut microbiome and promote healthy ageing. Nevertheless, prolongation of the health span of aged mice by remodelling the gut microbiome remains challenging.ResultsHere, we report the changes in gut microbial communities and their functions in mouse models during ageing and three rejuvenation procedures including co-housing, serum-injection and parabiosis. Our results showed that the compositional structure and gene abundance of the intestinal microbiota changed dynamically during the ageing process. Through the three rejuvenation procedures, we observed that the microbial community and intestinal immunity of aged mice were comparable to those of young mice. The results of metagenomic data analysis underscore the importance of the high abundance of Akkermansia and the butyrate biosynthesis pathway in the rejuvenated mouse group. Furthermore, oral administration of Akkermansia sufficiently ameliorated the senescence-related phenotype in the intestinal systems in aged mice and extended the health span, as evidenced by the frailty index and restoration of muscle atrophy.ConclusionsIn conclusion, the changes in key microbial communities and their functions during ageing and three rejuvenation procedures, and the increase in the healthy lifespan of aged mice by oral administration of Akkermansia. Our results provide a rationale for developing therapeutic strategies to achieve healthy active ageing.DWzth9x4bNysC3Pe8t3wT_Video abstract

The Impacts of Short-Term NMN Supplementation on Serum Metabolism, Fecal Microbiota, and Telomere Length in Pre-Aging Phase.

Aging is a natural process with concomitant changes in the gut microbiota and associate metabolomes. Beta-nicotinamide mononucleotide, an important NAD+ intermediate, has drawn increasing attention to retard the aging process. We probed the changes in the fecal microbiota and metabolomes of pre-aging male mice (C57BL/6, age: 16 months) following the oral short-term administration of nicotinamide mononucleotide (NMN). Considering the telomere length as a molecular gauge for aging, we measured this in the peripheral blood mononuclear cells (PBMC) of pre-aging mice and human volunteers (age: 45–60 years old). Notably, the NMN administration did not influence the body weight and feed intake significantly during the 40 days in pre-aging mice. Metabolomics suggested 266 upregulated and 58 downregulated serum metabolites. We identified 34 potential biomarkers linked with the nicotinamide, purine, and proline metabolism pathways. Nicotinamide mononucleotide significantly reduced the fecal bacterial diversity (p < 0.05) with the increased abundance of Helicobacter, Mucispirillum, and Faecalibacterium, and lowered Akkermansia abundance associated with nicotinamide metabolism. We propose that this reshaped microbiota considerably lowered the predicated functions of aging with improved immune and cofactors/vitamin metabolism. Most notably, the telomere length of PBMC was significantly elongated in the NMN-administered mice and humans. Taken together, these findings suggest that oral NMN supplementation in the pre-aging stage might be an effective strategy to retard aging. We recommend further studies to unravel the underlying molecular mechanisms and comprehensive clinical trials to validate the effects of NMN on aging.

Cereal Vinegar Sediment Alleviates Spontaneous Ulcerative Colitis in Il-10 Deficient Mice.

Cereal vinegar sediment (CVS) is precipitation generated during the preservation of vinegar. It has various functions such as anti-inflammatory, anti-tumor, hypoglycemic, and hypolipidemic. This study evaluates the effects of CVS on spontaneous colitis in Il-10-/- mice. CVS (1 g kg-1 body weight) is administered to mice for 42 days. CVS alleviated epithelium damage, inhibited myeloperoxidase (MPO) activity and malondialdehyde (MDA) level, decreased gene expression of tumor necrosis factor (Tnf )-a, inducible nitric oxide synthase (Inos), Interleukin(Il-23) in colon tissues is found. CVS also inhibited secretion of IL-2, IL-6, IL-13, Granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GMCSF), Interferon (IFN)-γ, and Regulated upon Activation, Normal T Cell Expressed and Presumably Secreted (RANTES) in serum. While CVS enhanced Regenerating Family Member 3 Gamma (Reg3γ), Mucin (Muc2, Muc3, and Muc4 gene expression, promoted intestinal epithelial cells to secrete Muc-2, and increased the content of acetic acid in intestinal tract of Il-10-/- mice. Additionally, CVS altered the composition of the gut microbiota by promoting the abundance of Akkermansia, Alistipes, and Lactobacillus, while inhibiting Desulfovibrio and Clostridium sensu stricto 1. These changes may be related to the regulation of steroid, fatty acids, and bile acid biosynthesis. This study demonstrated that CVS ameliorates spontaneous ulcerative colitis in Il-10-/- mice, which suggests CVS supplementation may serve as a protective dietary nutrient against colitis.

A common fungicide tebuconazole promotes colitis in mice via regulating gut microbiota

As a common fungicide, tebuconazole are ubiquitous in the natural environment and poses many potential risks. In this study, we examined the effects of exposure to tebuconazole on colitis in mice and explored its underlying mechanism. Specifically, exposure to tebuconazole could cause structural damage and inflammatory cell infiltration in colon tissue, activate the expression of inflammation-related genes, disrupt the expression of barrier function-related genes, and induce the colonic inflammation in mice. Similarly, exposure to tebuconazole could also exacerbate DSS-induced colitis in mice. In addition, we found that tebuconazole also could change the composition of the gut microbiota. In particular, tebuconazole significantly increases the relative abundance of Akkermansia of mice. Moreover, tebuconazole resulted in metabolic profiles disorders of the serum, leading to significant changes in the relative contents of metabolites involving glycolipid metabolism and amino acid metabolism. Particularly, the results of the gut microbiota transplantation experiment showed that exposure to tebuconazole could induced colonic inflammation in mice in a gut microbiota–dependent manner. Taken together, these results indicated that tebuconazole could induce colitis in mice via regulating gut microbiota. Our findings strongly support the concept that the gut microbiota is a key trigger of inflammatory bowel disease caused by pesticide intake.

Sequential Extraction, Characterization, and Analysis of Pumpkin Polysaccharides for Their Hypoglycemic Activities and Effects on Gut Microbiota in Mice.

This study aimed to extract polysaccharides from pumpkin, characterize the structures of four of them, and evaluate their in vitro antioxidant and hypoglycemic activities. Additionally, an animal model of type 2 diabetes mellitus (T2DM) was established and used to determine their hypoglycemic and hypolipidemic effects in vivo, and the underlying mechanisms related to the regulation of gut microbiota. Water-extracted crude pumpkin polysaccharides (W-CPPs), water extraction and alcohol precipitation crude pumpkin polysaccharides (WA-CPPs), deproteinized pumpkin polysaccharides (DPPs), and refined pumpkin polysaccharides (RPPs) were sequentially extracted and purified from pumpkin powder by hot water extraction, water extraction, and alcohol precipitation, deproteinization and DEAE-52 cellulose gel column, respectively. The extraction and purification methods had significant influence on the extraction yield, physicochemical properties, and in vitro antioxidant and hypoglycemic activities. W-CCP and RPPs had a significant positive free radical-scavenging capacities and inhibitory activities on α-glucosidase and α-amylase. RPP-3 not only inhibited the uptake of glucose in Caco-2 monolayer but also promoted the excretion of glucose, while RPP-2 had no inhibitory effect. Animal experiment results showed that W-CPP treatment significantly improved the T2DM symptoms in mice, which included lowering of fasting blood glucose (FBG), reducing insulin resistance (IR), and lowering of blood lipid levels. It increased the diversity of intestinal flora and reduced the harmful flora of model mice, which included Clostridium, Thermoanaerobe, Symbiotic bacteria, Deinococcus, Vibrio haematococcus, Proteus gamma, and Corio. At the family level, W-CPP (1,200 mg/kg) treatment significantly reduced the abundance of Erysipelotrichaceae, and the Akkermanaceae of Verrucobacterium became a biomarker. Pumpkin polysaccharides reshaped the intestinal flora by reducing Erysipelotrichaceae and increasing Akkermansia abundance, thereby improving blood glucose and lipid metabolism in the T2DM mice. Our results suggest that W-CCP and RPP-3 possess strong antioxidant and hypoglycemic activities, and are potential candidates for food additives or natural medicines.