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Gestational diabetes mellitus (GDM) is defined as "diagnosed as impaired glucose tolerance for the first time during pregnancy," which can lead to adverse pregnancy outcomes and produces divergent effects on mothers and newborns. In recent years, with the continuous expansion of obese people, GDM shows an upward trend. The abundant and diverse members of the human gut microbiota exert critical roles in the maintenance of human health. Studies have shown that GDM may be associated with disordered gut microbiota in both mothers and newborns. Taking into account the potential effects on maternal and consequently neonatal health, in this review, we analyzed the available data and discussed the current knowledge about the potential relationship between GDM and intestinal dysbiosis in mothers and newborns. In addition, we also discussed the influencing factors derived from GDM mothers on the gut microbiome of their newborns, including the vertical transmission of microbiota from mothers, the alteration of milk components of GDM mothers, and using of probiotics. Hoping that new insights into the role of the gut microbiota in GDM could lead to the development of integrated strategies to prevent and treat these metabolic disorders.
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OBJECTIVE: Diarrhea in infants is a serious gastrointestinal dysfunction characterized by vomiting and watery bowel movements. Without proper treatment, infants will develop a dangerous electrolyte imbalance. Diarrhea is accompanied by intestinal dysbiosis. This study compared the gut microbiota between healthy infants and diarrheic infants. It also investigated the effects of age and pathogen type on the gut microbiota of infants with diarrhea, providing data for the proper treatment for diarrhea in infants. MATERIALS AND METHODS: DNA was collected from the fecal samples of 42 Chinese infants with diarrhea and 37 healthy infants. The healthy infants and infants with diarrhea were divided into four age groups: 0-120, 120-180, 180-270, and 270-365 days. Using PCR and 16S rRNA high-throughput sequencing, the diarrhea-causing pathogens in these infants were identified and then categorized into four groups: Salmonella infection, Staphylococcus aureus infection, combined Salmonella and Staphylococcus aureus infection, and others (neither Salmonella nor Staphylococcus aureus). RESULTS: The species diversity of gut microbiota in diarrheic infants was significantly reduced compared with that in healthy infants. Infants with diarrhea had a lower abundance of Lactobacillus spp. and Bacillus spp. (P < 0.001) and a significant richness of Klebsiella spp. and Enterobacter spp. (P < 0.001). Similar gut microbiota patterns were found in diarrheic infants in all four age groups. However, different pathogenic infections have significant effects on the gut microbiota of diarrheic infants. For instance, the relative abundance of Klebsiella spp. and Streptococcus spp. was significantly increased (P < 0.001) in infants infected with Staphylococcus aureus; meanwhile, the richness of bacteria such as Enterobacter spp. was significantly increased in the Salmonella infection group (P < 0.001). CONCLUSION: The microbiota in infants with diarrhea has changed significantly, characterized by decreased species diversity and abundance of beneficial bacteria and significant increase in the proportion of conditional pathogens. Meanwhile, the gut microbiota of infants with diarrhea at different ages was similar, but different pathogenic infections affect the gut microbiota characteristics. Therefore, early identification of changes in gut microbiota in infants with diarrhea and the adoption of appropriate pathogen type-specific interventions may effectively alleviate the disease and reduce adverse reactions.
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The regulatory mechanism of tautomycetin (TMC) biosynthesis remains largely unknown, although it has been of great interest to the pharmaceutical industry. Our previous study showed that intracellular adenosine triphosphate (inATP) level is negatively correlated with secondary metabolite biosynthesis in various Streptomyces spp. In this study, by exogenous treatment of ATP, we also found a negative correlation between TMC biosynthesis and inATP level in Streptomyces griseochromogenes (S. griseochromogenes). However, the underlying mechanism remains unclear. TmcN, a pathway-specific transcriptional regulator of TMC biosynthetic genes, was previously revealed as a large ATP-binding LuxR (LAL) family protein. The predicted amino acid sequence of TmcN shows highly conserved Walker A and B binding motifs, which suggest an ATPase function of TmcN. We therefore hypothesized that the ATPase domain of TmcN may play a role in sensing endogenous pool of ATP, and is thus involved in the ATP regulation of TMC biosynthesis. To test the hypothesis, we first explored the key residue that affects the ATPase activity of TmcN by amino acid sequence alignment and structural simulation. After that, we disrupted tmcN gene in S. griseochromogenes, and the tmcN or site-direct-mutated tmcN were re-introduced to get the complementary and ATPase domain disrupted strains. The transcription level of tmcN, TMC yield, and inATP, as well as the effect of ATP on TMC production of different mutants were evaluated. Deletion of tmcN or site-direct mutation of ATPase domain of TmcN in S. griseochromogenes significantly reduced the TMC production, and it was not affected by exogenous ATP treatment. In addition, a relatively high level of inATP was detected in tmcN deletion and site-direct mutation strains. Our results here suggested that TmcN, especially its ATPase domain, is involved in consuming of endogenous ATP pool and thus plays pivotal role in connecting the primary and secondary metabolite in S. griseochromogenes.
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Trifosfato de Adenosina/metabolismo , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica/fisiologia , Lipídeos/biossíntese , Streptomyces griseus/metabolismo , Fatores de Transcrição/metabolismo , FuranosRESUMO
BACKGROUND: An increased prevalence of allergic disorders in developed countries has been associated with decreased exposure to environmental micro-organisms and an alteration of microbiota colonization. An appropriate model is needed to investigate the mechanisms by which hygiene environment-driven changes in microbiota could regulate allergic disorders. OBJECTIVE: To discover the correlation between the higher incidence and severity of allergies with the relative hygiene environment in a developed country. METHODS: Allergic respiratory inflammation was induced in specific pathogen-free and control rats by sensitization and challenge with ovalbumin. The diversity of lower airway bacteria community was analyzed by polymerase chain reaction denaturing gradient gel electrophoresis and sequencing before ovalbumin sensitization. Allergic respiratory inflammation resulting in cellular infiltrate was measured after the last challenge. RESULTS: The diversity of microbiota in the airway of specific pathogen-free rats decreased compared with the control rats; the more frequent microbiota in the control rats were Proteobacteria and Bacteroidetes. In addition, increased nasal rubbing and sneezing combined with exaggerated IgE production and leukocyte number was observed in ovalbumin-treated specific pathogen-free rats. CONCLUSION: These data indicate that the excessive "hygienic" environment resulted in a decreased bacterial diversity in the airway during infancy, leading to an increased susceptibility to allergic disease.
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Microbiota , Hipersensibilidade Respiratória/microbiologia , Sistema Respiratório/microbiologia , Alérgenos/administração & dosagem , Alérgenos/imunologia , Alérgenos/toxicidade , Animais , Quimiocinas/genética , Suscetibilidade a Doenças , Tolerância Imunológica , Imunização , Incidência , Injeções Subcutâneas , Ovalbumina/administração & dosagem , Ovalbumina/imunologia , Ovalbumina/toxicidade , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Wistar , Hipersensibilidade Respiratória/epidemiologia , Hipersensibilidade Respiratória/imunologia , Organismos Livres de Patógenos Específicos , SimbioseRESUMO
Hyperuricemia is a prevalent metabolic disorder that arises from abnormal purine metabolism and reduced excretion of uric acid (UA). The gut microbiota plays a significant role in the biosynthesis and excretion of UA. Probiotics capable of purine degradation possess the potential to prevent hyperuricemia. Our study aimed to screen probiotics in areas with abundant dairy products and longevity populations in China, which could attenuate the level of UA and explore the underlying mechanism. In this study, twenty-three lactic acid bacteria isolated from healthy Chinese infant feces and traditional fermented foods such as hurood and lump milk were evaluated for the ability to tolerance acid, bile, artificial gastric juice, and artificial intestinal juice to determine the potential of the candidate strains as probiotics. Eight strains were identified as possessing superior tolerance to simulated intestinal conditions and were further analyzed by high-performance liquid chromatography (HPLC), revealing that Limosilactobacillus reuteri HCS02-001 (Lact-1) and Lacticaseibacillus paracasei HCS17-040 (Lact-2) possess the most potent ability to degrade purine nucleosides. The effect of Lact-1 and Lact-2 on hyperuricemia was evaluated by intervening with them in the potassium oxonate and adenine-induced hyperuricemia Balb/c mice model in vivo. Our results showed that the level of serum UA in hyperuricemic mice can be efficiently reduced via the oral administration of Lact-1 (p < 0.05). It significantly inhibited the levels of liver inflammatory cytokines and hepatic xanthine oxidase through a TLR4/MyD88/NF-κB pathway across the gut-liver axis. Furthermore, UA transporters ABCG2 and SLC2A9 were substantially upregulated by the intervention of this probiotic. Fecal ATP levels were significantly induced, while fecal xanthine dehydrogenase and allantoinase levels were increased following probiotics. RNA sequencing of HT-29 cells line treated with Lact-1 and its metabolites demonstrated significant regulation of pathways related to hyperuricemia. In summary, these findings demonstrate that Limosilactobacillus reuteri HCS02-001 possesses a capacity to ameliorate hyperuricemia by inhibiting UA biosynthesis via enhancing gastrointestinal barrier functions and promoting UA removal through the upregulation of urate transporters, thereby providing a basis for the probiotic formulation by targeting the gut microbiota.
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Human milk oligosaccharides (HMOs) are vital milk carbohydrates that help promote the microbiota-dependent growth and immunity of infants. Sialic acid (SA) is a crucial component of sialylated milk oligosaccharides (S-MOs); however, the effects of SA supplementation in lactating mothers on S-MO biosynthesis and their breastfed infants are unknown. Probiotic intervention during pregnancy or lactation demonstrates promise for modulating the milk glycobiome. Here, we evaluated whether SA and a probiotic (Pro) mixture could increase S-MO synthesis in lactating mothers and promote the microbiota development of their breastfed neonates. The results showed that SA+Pro intervention modulated the gut microbiota and 6'-SL contents in milk of maternal rats more than the SA intervention, which promoted Lactobacillus reuteri colonization in neonates and immune development. Deficient 6'-SL in the maternal rat milk of St6gal1 knockouts (St6gal1-/-) disturbed intestinal microbial structures in their offspring, thereby impeding immune tolerance development. SA+Pro intervention in lactating St6gal1± rats compromised the allergic responses of neonates by promoting 6'-SL synthesis and the neonatal gut microbiota. Our findings from human mammary epithelial cells (MCF-10A) indicated that the GPR41-PI3K-Akt-PPAR pathway helped regulate 6'-SL synthesis in mammary glands after SA+Pro intervention through the gut - breast axis. We further validated our findings using a human-cohort study, confirming that providing SA+Pro to lactating Chinese mothers increased S-MO contents in their breast milk and promoted gut Bifidobacterium spp. and Lactobacillus spp. colonization in infants, which may help enhance immune responses. Collectively, our findings may help alter the routine supplementation practices of lactating mothers to modulate milk HMOs and promote the development of early-life gut microbiota and immunity.
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Microbioma Gastrointestinal , Ácido N-Acetilneuramínico , Feminino , Lactente , Gravidez , Humanos , Animais , Ratos , Lactação , Estudos de Coortes , Fosfatidilinositol 3-Quinases , Leite Humano , ImunidadeRESUMO
Whether or not treatment with antibiotics or probiotics for bacterial vaginosis (BV) is associated with a change in the diversity of vaginal microbiota in women was investigated. One hundred fifteen women, consisting of 30 healthy subjects, 30 BV-positive control subjects, 30 subjects with BV treated with a 7-day metronidazole regimen, and 25 subjects with BV treated with a 10-day probiotics regimen, were analyzed to determine the efficacy and disparity of diversity and richness of vaginal microbiota using 454 pyrosequencing. Follow-up visits at days 5 and 30 showed a greater BV cure rate in the probiotics-treated subjects (88.0 and 96 %, respectively) compared to the metronidazole-treated subjects (83.3 and 70 %, respectively [p = 0.625 at day 5 and p = 0.013 at day 30]). Treatment with metronidazole reduced the taxa diversity and eradicated most of the BV-associated phylotypes, while probiotics only suppressed the overgrowth and re-established vaginal homeostasis gradually and steadily. Despite significant interindividual variation, the microbiota of the actively treated groups or participants constituted a unique profile. Along with the decrease in pathogenic bacteria, such as Gardnerella, Atopobium, Prevotella, Megasphaera, Coriobacteriaceae, Lachnospiraceae, Mycoplasma, and Sneathia, a Lactobacillus-dominated vaginal microbiota was recovered. Acting as vaginal sentinels and biomarkers, the relative abundance of Lactobacillus and pathogenic bacteria determined the consistency of the BV clinical and microbiologic cure rates, as well as recurrent BV. Both 7-day intravaginal metronidazole and 10-day intravaginal probiotics have good efficacy against BV, while probiotics maintained normal vaginal microbiota longer due to effective and steady vaginal microbiota restoration, which provide new insights into BV treatment.
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Metagenoma/efeitos dos fármacos , Metronidazol/administração & dosagem , Probióticos/administração & dosagem , Vagina/microbiologia , Vaginose Bacteriana/tratamento farmacológico , Administração Intravaginal , Bactérias/classificação , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Bactérias/isolamento & purificação , Estudos de Coortes , Feminino , Humanos , Lactobacillus/genética , Lactobacillus/isolamento & purificação , Lactobacillus/fisiologia , Dados de Sequência Molecular , Filogenia , Resultado do Tratamento , Vaginose Bacteriana/microbiologiaRESUMO
The aim of this study was to evaluate the effect of Lactobacillus delbrueckii subsp. lactis (L.del) on vaginal microbiota (VM) dysbiosis and vaginal radiation injury in gynecologic cancer patients. The inhibitory effects of L.del on cervical cancer cells were also studied in vitro. Gynecologic cancer patients receiving radiotherapy were randomized into control and L.del intervention groups. The control group received radiotherapy, while the intervention group received radiotherapy and L.del intervention (1 capsule/day placed into the deep vagina from the first day of radiotherapy until the end of treatment). Vaginal swab samples were collected on the first day pre-treatment and the last day post-treatment. DNA from 54 patients was extracted and assessed by the 16S rRNA sequencing method. Radiotherapy resulted in vaginal microbiome dysbiosis characterized by increased phylogenetic diversity and increased abundance of Brevundimonas, Streptococcus and Prevotella, but a decreased abundance of Lactobacillus. Level 2 vaginal radiation injury was positively associated with the abundance of Brevundimonas and gram-negative non-fermenting bacteria. Administration of L.del attenuated the reduction of Lactobacillus while also inhibiting the abundance of Streptococcus and Prevotella, thereby ameliorating radiotherapy-related vaginal microbiota dysbiosis. CLD inhibited the in vitro proliferation of SiHa cells by altering the expression of BCL2, HPV16-E6, HPV16-E7, IL6, MAP7, BAX, Caspase-3, Caspase-9 and LTF. In conclusion, L. del application can alleviate radiation-induced vaginal dysbiosis and restore Lactobacillus dominance of the vaginal microbiome. Moreover, CLD was found to inhibit cell growth and promote the apoptosis of SiHa cells in vitro. The registration number for this clinical trial is ChiCTR1900021784.
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Disbiose , Neoplasias , Feminino , Humanos , Disbiose/microbiologia , RNA Ribossômico 16S/genética , Filogenia , Vagina/microbiologia , Lactobacillus/genética , Streptococcus/genéticaRESUMO
Gestational diabetes mellitus (GDM) is an increasing public health concern that significantly increases the risk of early childhood allergic diseases. Altered maternal milk glycobiome may strongly affect gut microbiota and enteric-specific Treg cell-mediated development of immune tolerance in GDM infants. In this study, we found that, compared with healthy Chinese mothers, mothers with GDM had significantly lower levels of total and specific human milk oligosaccharides (HMOs) in their colostrum that subsequently increased with extension of lactation. This alteration in HMO profiles significantly delayed colonization of Lactobacillus and Bifidobacterium spp. in their breast-fed infants, resulting in a distinct gut microbial structure and metabolome. Further experiments in GDM mouse models indicated that decreased contents of milk oligosaccharides, mainly 3'-sialyllactose (3'-SL), in GDM maternal mice reduced colonization of bacteria, such as L. reuteri and L. johnsonii, in the neonatal gut, which impeded development of RORγt+ regulatory T (Treg) cell-mediated immune tolerance. Treatment of GDM neonates with 3'-SL, Lactobacillus reuteri (L. reuteri) and L. johnsonii promoted the proliferation of enteric Treg cells and expression of transcription factor RORγt, which may have contributed to compromising ovalbumin (OVA)-induced allergic responses. In vitro experiments showed that 3'-SL, metabolites of L. johnsonii, and lysates of L. reuteri stimulated differentiation of mouse RORγt+ Treg cells through multiple regulatory effects on Toll-like receptor, MAPK, p53, and NOD-like receptor signaling pathways. This study provides new ideas for the development of gut microbiota and immune tolerance in GDM newborns.
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Diabetes Gestacional , Microbioma Gastrointestinal , Pré-Escolar , Recém-Nascido , Lactente , Feminino , Gravidez , Humanos , Animais , Camundongos , Linfócitos T Reguladores , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares , Mães , Leite Humano , BactériasRESUMO
BACKGROUND: Probiotic fermentation is a promising strategy for improving the nutritional and functional properties of traditional Chinese medicines (TCMs). Ganoderma lucidum and Raphani Semen are famous TCMs that have been shown to help alleviate immune system disorders. However, few studies have experimentally investigated the effects of probiotic-fermented G.lucidum and Raphani Semen on the immune system. PURPOSE: We established the in vitro fermentation of G. lucidum and Raphani Semen with a probiotic mixture (Bifidobacterium longum, Lactobacillus acidophilus, and l. fermentum) (GRFB), investigated its ameliorating effect against cyclophosphamide (CTX)-induced immunosuppression, and explored its possible mechanisms. METHODS: First, the different components in GRFB were identified by high-performance liquid chromatography. Second, its immune-stimulatory activities were evaluated in CTX-treated mice. Lastly, its possible in vitro and in vivo mechanisms were studied. RESULTS: Probiotic fermentation of G. lucidum and Raphani Semen altered some of its chemical constituents, potentially helping improve the ability of GRFB to alleviate immunosuppression. As expected, GRFB effectively ameliorated CTX-induced immunosuppression by increasing the number of splenic lymphocytes and regulating the secretion of serum and ileum cytokines. GRFB supplementation also effectively improved intestinal integrity in CTX-treated mice by upregulating tight junction proteins. It also protects against CTX-induced intestinal dysbiosis by increasing the abundance of beneficial bacteria and reducing the abundance of harmful bacteria. GRFB could directly promote intestinal immunity but not systemic immunity in vitro, suggesting a microbiota-dependent regulation of GRFB. Interestingly, cohousing CTX-induced immunosuppressed mice with GRFB-treated mice promoted their symptoms recovery. Enhanced CTX-induced immunosuppression by GRFB in vitro depended on the gut microbiota. Remarkably, a Kyoto Encyclopedia of Genes and Genomes analysis showed that the GRFB-reprogrammed microbiota was significantly enriched in DNA damage repair pathways, which contribute to repairing the intestinal mucosal barrier. CONCLUSION: This is the first study to suggest that compare with unfermented G. lucidum and Raphani Semen, GRFB can more effectively promote intestinal immunity and manipulate the gut microbiota to promote immunostimulatory activity and repair immunosuppression-induced intestinal barrier damage by biotransforming G.lucidum and Raphani Semen components.
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Microbioma Gastrointestinal , Probióticos , Reishi , Animais , Camundongos , Fermentação , Probióticos/farmacologia , Probióticos/uso terapêutico , Ciclofosfamida/efeitos adversos , Imunidade , Terapia de Imunossupressão , SementesRESUMO
BACKGROUND: Omega-3 polyunsaturated fatty acids (PUFAs) play beneficial roles in metabolism and health. Little is known about the effects of different doses of omega-3 PUFAs on gut microbiota. OBJECTIVE: In this study, we focus on the effects of different doses of omega-3 PUFAs on gut microbiota and immunity. DESIGN: BALB/c mice was first treated with ceftriaxone sodium for 7 days, and then they received saline or different doses of omega-3 PUFAs (30, 60 and 90 mg omega-3 PUFAs) via daily gavage for 21 days. Alterations of cecum microbiota; the tight junction proteins, zonula occludens 3 (ZO3) and occludin, in the ileal wall; serum lipopolysaccharide (LPS); Interleukin-10 (IL-10), interleukin-1ß (IL-1ß), and Tumour Necrosis Factor α (TNF-α) ; mucus SIgA levels were measured. RESULTS: Compared with the ceftriaxone sodium administration group, significant increases in bacterial richness and diversity were observed in the 60- and 90-mg omega-3 PUFA groups, while only a slight increase was observed in the 30-mg omega-3 PUFA group. A higher percentage of several genera, including Lactobacillus, Helicobacter, and Ruminococcus, and a lower percentage of Bacteroides, Clostridium, and Prevotella were observed in the 60- and 90-mg omega-3 PUFA groups when compared with those in the 30-mg group. The expression of ZO3 and occludin proteins increased in 60- and 90-mg omega-3 PUFA groups compared with the natural recovery group. The mucus SIgA and serum IL-10 levels were increased, and serum levels of LPS, IL-1ß, and TNF-α were decreased in the 60- and 90-mg omega-3 PUFA groups when compared with those in the ceftriaxone sodium-treated group. CONCLUSION: Different doses of omega-3 PUFAs have different therapeutic effects on the intestinal microbiota. The 60- and 90-mg omega-3 PUFA supplementation had better recovery effects on the gut microbiota and immunity than those of the 30 mg omega-3 PUFAs supplementation.
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Breast milk is rich in sialic acids (SA), which are commonly combined with milk oligosaccharides and glycoconjugates. As a functional nutrient component, SA-containing milk components have received increasing attention in recent years. Sialylated human milk oligosaccharides (HMOs) have been demonstrated to promote the growth and metabolism of beneficial gut microbiota in infants, bringing positive outcomes to intestinal health and immune function. They also exhibit antiviral and bacteriostatic activities in the intestinal mucosa of new-borns, thereby inhibiting the adhesion of pathogens to host cells. These properties play a pivotal role in regulating the intestinal microbial ecosystem and preventing the occurrence of neonatal inflammatory diseases. In addition, some recent studies also support the promoting effects of sialylated HMOs on neonatal bone and brain development. In addition to HMOs, sialylated glycoproteins and glycolipids are abundant in milk, and are also critical to neonatal health. This article reviews the current research progress in the regulation of sialylated milk oligosaccharides and glycoconjugates on neonatal gut microbiota and health.
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Vaginal dysbiosis often occurs in patients with cervical cancer. The fucosylation of mucosal epithelial cells is closely related to microbial colonization, and play an important role in protecting the vaginal mucosal epithelial cells. However, no reports on the relationship between vaginal dysbiosis and abnormal mucosal epithelial cell fucosylation, and their roles in the occurrence and development of cervical cancer are unavailable. Here we report that core fucosylation levels were significantly lower in the serum, exfoliated cervical cells and tumor tissue of cervical cancer patients. Core fucosyltransferase gene (Fut8) knockout promoted the proliferation and migration of cervical cancer cells. In patients with cervical cancer, the vaginal dysbiosis, and the abundance of Lactobacillus, especially L. iners, was significantly reduced. Meanwhile, the abundance of L.iners was positively correlated with core fucosylation levels. The L. iners metabolite lactate can activate the Wnt pathway through the lactate-Gpr81 complex, which increases the level of core fucosylation in epidermal cells, inhibiting the proliferation and migration of cervical cancer cells, and have application prospects in regulating the vaginal microecology and preventing cervical cancer.
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Células Epiteliais/metabolismo , Fucosiltransferases/metabolismo , Lactobacillus/patogenicidade , Neoplasias do Colo do Útero/microbiologia , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Microambiente TumoralRESUMO
Ganoderma lucidum is a legendary traditional Chinese medicine with various bioactivities. This study was conducted (a) to explore the in vitro fermentation of the water extracts of G. lucidum fruiting body with Lactobacillus acidophilus and Bifidobacterium breve and (b) to investigate the effect of fermentation broth (GLFB) on dexamethasone (DEX)-induced immunosuppressed mice. Our results demonstrated that probiotic fermentation of G. lucidum fruiting body extracts underwent structural changing of major ganoderic acid components, such as ganoderic acid A (GA) into GC2, and this fermentation process involves changing of several metabolic pathways in the probiotic strains. GLFB could significantly improve the immunity, intestinal integrity, and gut microbiota dysbiosis in DEX-treated mice, and the immunostimulatory activity of GLFB was found closely related to its direct regulation on the expansion of CD4+ T cells in Peyer's patches of mice. These data implied that probiotic fermentation of G. lucidum fruiting body extracts promoted its immunostimulatory activity via biotransformation of components such as GA. This research provides a theoretical support for the development and application of G. lucidum fermentation by probiotics.
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Adjuvantes Imunológicos/farmacologia , Dexametasona/farmacologia , Carpóforos/química , Imunossupressores/farmacologia , Probióticos/metabolismo , Reishi/metabolismo , Animais , Linfócitos T CD4-Positivos/metabolismo , Fermentação , Microbioma Gastrointestinal/efeitos dos fármacos , Ácidos Heptanoicos/farmacologia , Intestinos/efeitos dos fármacos , Lanosterol/análogos & derivados , Lanosterol/farmacologia , Contagem de Linfócitos , Masculino , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos BALB C , Nódulos Linfáticos Agregados/citologia , Nódulos Linfáticos Agregados/efeitos dos fármacos , Reishi/químicaRESUMO
This study aimed at determining the beneficial effect of Clostridium butyricum (CB) RH2 on ceftriaxone-induced dysbacteriosis. To this purpose, BALB/c mice were exposed to ceftriaxone (400 mg/ml) or not (control) for 7 days, and administered a daily oral gavage of low-, and high-dose CB RH2 (108 and 1010 CFU/ml, respectively) for 2 weeks. CB RH2 altered the diversity of gut microbiota, changed the composition of gut microbiota in phylum and genus level, decreased the F/B ratio, and decreased the pro-inflammatory bacteria (Deferribacteres, Oscillibacter, Desulfovibrio, Mucispirillum and Parabacteroides) in ceftriaxone-treated mice. Additionally, CB RH2 improved colonic architecture and intestinal integrity by improving the mucous layer and the tight junction barrier. Furthermore, CB RH2 also mitigated intestinal inflammation through decreasing proinflammatory factors (TNF-α and COX-2) and increasing anti-inflammatory factors (IL-10). CB RH2 had direct effects on the expansion of CD4+ T cells in Peyer's patches (PPs) in vitro, which in turn affected their immune response upon challenge with ceftriaxone. All these data suggested that CB RH2 possessed the ability to modulate the intestinal mucosal and systemic immune system in limiting intestinal alterations to relieve ceftriaxone-induced dysbacteriosis.
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Clostridium butyricum , Disbiose , Animais , Ceftriaxona , Mucosa Intestinal , Intestinos , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Gut dysbiosis induced by high-fat diet (HFD) may result in low-grade inflammation leading to diverse inflammatory diseases. The beneficial effects of probiotics and prebiotics on obesity have been reported previously. However, their benefits in promoting human health and the underlying mechanisms still need to be further characterized. This study is aimed at understanding how probiotic Bacillus licheniformis Zhengchangsheng® (BL) and prebiotic xylooligosaccharides (XOS) influence the health of a rat model with HF (60 kcal %) diet-induced obesity. Five groups of male Sprague Dawley (SD) rats were fed a normal fat diet (CON) or an HFD with or without BL and XOS supplementation for 3 weeks. Lipid profiles, inflammatory biomarkers, and microbiota composition were analyzed at the end of the experiment. Rats fed an HFD exhibited increased body weight and disordered lipid metabolism. In contrast, combined BL and XOS supplementation inhibited body weight gain and returned lipid metabolism to normal. Furthermore, BL and XOS administration changed the gut microbiota composition and modulated specific bacteria such as Prevotellaceae, Desulfovibrionaceae, and Ruminococcaceae. In addition, supplements of combined BL and XOS obviously reduced the serum LPS level, which was significantly related to microbial variations. Our findings suggest that modulation of the gut microbiota as a result of probiotic BL and prebiotic XOS supplementation has a positive effect on HFD-induced obesity in rats.
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Bacillus licheniformis , Microbioma Gastrointestinal/efeitos dos fármacos , Glucuronatos , Obesidade , Oligossacarídeos , Probióticos , Administração Oral , Animais , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Medicamentos de Ervas Chinesas , Glucuronatos/administração & dosagem , Glucuronatos/farmacologia , Masculino , Obesidade/metabolismo , Obesidade/microbiologia , Oligossacarídeos/administração & dosagem , Oligossacarídeos/farmacologia , Prebióticos/administração & dosagem , Probióticos/administração & dosagem , Probióticos/farmacologia , Ratos , Ratos Sprague-Dawley , Aumento de Peso/efeitos dos fármacosRESUMO
Constipation is one of the most common functional gastrointestinal disorders accompanied with intestinal dysbiosis. Laxatives for constipation usually have side effects. Bee honey is a natural food with unique composition, antimicrobial properties, and bifidogenic effect. In order to assess whether honey can ameliorate loperamide-induced constipation in BALB/c mice through the alteration of the gut microbiota, the present study was undertaken. Mice were given Jarrah honey (7.5 g/kg body weight) by gavage once per day for 5 days. Fecal water content, intestinal transit rate together with the colon concentrations of substance P (SP), vasoactive intestinal peptide (VIP), and serotonin (5-hydroxytryptamine; 5-HT) were evaluated. Furthermore, we determined the effect of honey treatment on gut microbiota in mice using stool genomic 16S rRNA sequencing. As a result, honey showed an obvious improvement in fecal water content and alleviated constipation by modulating the microbial composition of the microbiota, and this was highly associated with a proportional decrease in gut Desulfovibrio. In addition, we found that the colon level of neurotransmitters SP and VIP was significantly related to microbial variations. Our results indicate that gut microbiota is involved in the alleviation of loperamide-induced constipation by honey supplementation in mice, and it could be considered as an evaluating parameter in constipation therapy strategies.
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OBJECTIVE: High fructose consumption exacerbates purine degradation and intestinal dysbiosis, which are closely related to the development of hyperuricemia. Probiotics are powerful weapons to combat metabolic disturbance and intestinal dysbiosis. Previously we isolated a Lactobacillus strain named DM9218 that could reduce the serum uric acid (UA) level by assimilating purine nucleosides. The present study aimed to evaluate the effects of DM9218 on high-fructose-induced hyperuricemia and to elucidate the underlying mechanisms. METHODS: Mice were fed a normal diet, a high-fructose diet, or high-fructose diet with DM9218. Metabolic parameters, fructose- and UA-related metabolites, and fecal microbiota were investigated. Whole-genome sequencing of strain DM9218 was also conducted. In addition, an inosine hydrolase from DM9218 was heterologously expressed in Escherichia coli, and its inosine-degrading activity was detected. RESULTS: Our results indicated that DM9218 could decrease serum UA level and hepatic xanthine oxidase activity in fructose-fed mice. It could protect against high-fructose-induced liver damage and retard UA accumulation by degrading inosine. The modulation effect of DM9218 on high-fructose-induced intestinal dysbiosis resulted in enhancement of intestinal barrier function and reduction of liver lipopolysaccharide, which was closely correlated with the down-regulation of inflammatory cytokine-stimulated xanthine oxidase expression and activity. CONCLUSIONS: Lactobacillus brevis DM9218 is a probiotic strain with the potential to ameliorate fructose-induced hyperuricemia.
Assuntos
Disbiose/tratamento farmacológico , Frutose/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Hiperuricemia/tratamento farmacológico , Inosina/metabolismo , Levilactobacillus brevis , Animais , Dieta/efeitos adversos , Dieta/métodos , Modelos Animais de Doenças , Disbiose/metabolismo , Disbiose/urina , Hiperuricemia/etiologia , Hiperuricemia/urina , Inosina/urina , Intestinos/efeitos dos fármacos , Intestinos/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , ProbióticosRESUMO
Intestinal bacterial dysbiosis has been increasingly linked to ankylosing spondylitis (AS), which is a prototypic and best studied subtype of spondyloarthritis (SpA). Fungi and bacteria coexist in the human gut and interact with each other. Although they have been shown to contribute actively to health or disease, no studies have investigated whether the fungal microbiota in AS patients is perturbed. In this study, fecal samples from 22 AS patients, with clinical and radiographic assessments, and 16 healthy controls (HCs) were collected to systematically characterize the gut microbiota and mycobiota in AS patients by 16S rRNA gene- and ITS2-based DNA sequencing. Our results showed that the microbiota of AS patients was characterized by increased abundance of Proteobacteria and decreased Bacteroidetes, which was contributed by enrichment of Escherichia-Shigella, Veillonella, Lachnospiraceae NK4A136 group, and reduction of Prevotella strain 9, Megamona, and Fusobacterium. The gut mycobiota of AS patients was characterized by higher levels of Ascomycota, especially the class of Dothideomycetes, and decreased abundance of Basidiomycota, which was mainly contributed by the decease of Agaricales. Compared to HCs, decreased ITS2/16S biodiversity ratios and altered bacterial-fungal interkingdom networks were observed in AS patients. Compared with nonsteroidal anti-inflammatory drugs (NSAIDs), treating AS patients with biological agents induced obvious changes in the gut mycobiota, and this result was highly associated with disease activity indexes, including AS disease activity index (ASDAS) C-reactive protein (asCRP), erythrocyte sedimentation rate (ESR), and Bath AS disease activity index (BASDAI). In addition, altered mycobiota in AS patients was also found associated with the degree of radiographic damage. IMPORTANCE The human gut is colonized by diverse fungi (mycobiota), and fungi have long been suspected in the pathogenesis of SpA. Our study unraveled a disease-specific interkingdom network alteration in AS, suggesting that fungi, or the interkingdom interactions between bacteria and fungi, may play an essential role in AS development. However, our study is limited by sample size, and in-depth mechanism studies and additional large-scale investigations characterizing the gut mycobiome in AS patients are needed to form a foundation for research into the relationship between mycobiota dysbiosis and AS development.
RESUMO
The maternal milk glycobiome is crucial for shaping the gut microbiota of infants. Although high core fucosylation catalyzed by fucosyltransferase 8 (Fut8) is a general feature of human milk glycoproteins, its role in the formation of a healthy microbiota has not been evaluated. In this study, we found that the core-fucosylated N-glycans in milk of Chinese mothers selectively promoted the colonization of specific gut microbial groups, such as Bifidobacterium spp. and Lactobacillus spp. in their breast-fed infants during lactation. Compared with Fut8+/+ (WT) mouse-fed neonates, the offspring fed by Fut8+/- maternal mice had a distinct gut microbial profile, which was featured by a significant reduction of Lactobacillus spp., Bacteroides spp., and Bifidobacterium spp. and increased abundance of members of the Lachnospiraceae NK4A136 group and Akkermansia spp. Moreover, these offspring mice showed a lower proportion of splenic CD19+ CD69+ B lymphocytes and attenuated humoral immune responses upon ovalbumin (OVA) immunization. In vitro studies demonstrated that the chemically synthesized core-fucosylated oligosaccharides possessed the ability to promote the growth of tested Bifidobacterium and Lactobacillus strains in minimal medium. The resulting L-fucose metabolites, lactate and 1,2-propanediol, could promote the activation of B cells via the B cell receptor (BCR)-mediated signaling pathway.IMPORTANCE This study provides novel evidence for the critical role of maternal milk protein glycosylation in shaping early-life gut microbiota and promoting B cell activation of neonates. The special core-fucosylated oligosaccharides might be promising prebiotics for the personalized nutrition of infants.