Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 15.732
Filtrar
1.
BMC Microbiol ; 24(1): 156, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724913

RESUMO

BACKGROUND: To establish a method to induce Campylobacter jejuni colonization in the intestines of C57BL/6 mice through antibiotic-induced microbiome depletion. RESULTS: Fifty-four female C57BL/6 mice were divided into the normal, control, and experimental groups. The experimental group was administered intragastric cefoperazone sodium and sulbactam sodium (50 mg/mL) for 2 days; then, the experimental and control mice were intragastrically administered 200 µL C. jejuni, which was repeated once more after 2 days. Animal feces were collected, and the HipO gene of C. jejuni was detected using TaqMan qPCR from day 1 to day 14 after modeling completion. Immunofluorescence was used to detect intestinal C. jejuni colonization on day 14, and pathological changes were observed using hematoxylin and eosin staining. Additionally, 16S rDNA analyses of the intestinal contents were conducted on day 14. In the experimental group, C. jejuni was detected in the feces from days 1 to 14 on TaqMan qPCR, and immunofluorescence-labeled C. jejuni were visibly discernable in the intestinal lumen. The intestinal mucosa was generally intact and showed no significant inflammatory-cell infiltration. Diversity analysis of the colonic microbiota showed significant inter-group differences. In the experimental group, the composition of the colonic microbiota differed from that in the other 2 groups at the phylum level, and was characterized by a higher proportion of Bacteroidetes and a lower proportion of Firmicutes. CONCLUSIONS: Microbiome depletion induced by cefoperazone sodium and sulbactam sodium could promote long-term colonization of C. jejuni in the intestines of mice.


Assuntos
Antibacterianos , Infecções por Campylobacter , Campylobacter jejuni , Cefoperazona , Fezes , Microbioma Gastrointestinal , Camundongos Endogâmicos C57BL , RNA Ribossômico 16S , Sulbactam , Animais , Campylobacter jejuni/efeitos dos fármacos , Campylobacter jejuni/crescimento & desenvolvimento , Feminino , Antibacterianos/farmacologia , Cefoperazona/farmacologia , Fezes/microbiologia , Infecções por Campylobacter/microbiologia , Camundongos , Microbioma Gastrointestinal/efeitos dos fármacos , Sulbactam/farmacologia , RNA Ribossômico 16S/genética , Intestinos/microbiologia , Colo/microbiologia , Colo/patologia , Modelos Animais de Doenças , Mucosa Intestinal/microbiologia , Mucosa Intestinal/efeitos dos fármacos , DNA Bacteriano/genética , DNA Ribossômico/genética
2.
Gut Microbes ; 16(1): 2347722, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38706205

RESUMO

The intestine is prone to radiation damage in patients undergoing radiotherapy for pelvic tumors. However, there are currently no effective drugs available for the prevention or treatment of radiation-induced enteropathy (RIE). In this study, we aimed at investigating the impact of indole-3-carboxaldehyde (I3A) derived from the intestinal microbiota on RIE. Intestinal organoids were isolated and cultivated for screening radioprotective tryptophan metabolites. A RIE model was established using 13 Gy whole-abdominal irradiation in male C57BL/6J mice. After oral administration of I3A, its radioprotective ability was assessed through the observation of survival rates, clinical scores, and pathological analysis. Intestinal stem cell survival and changes in the intestinal barrier were observed through immunofluorescence and immunohistochemistry. Subsequently, the radioprotective mechanisms of I3A was investigated through 16S rRNA and transcriptome sequencing, respectively. Finally, human colon cancer cells and organoids were cultured to assess the influence of I3A on tumor radiotherapy. I3A exhibited the most potent radioprotective effect on intestinal organoids. Oral administration of I3A treatment significantly increased the survival rate in irradiated mice, improved clinical and histological scores, mitigated mucosal damage, enhanced the proliferation and differentiation of Lgr5+ intestinal stem cells, and maintained intestinal barrier integrity. Furthermore, I3A enhanced the abundance of probiotics, and activated the AhR/IL-10/Wnt signaling pathway to promote intestinal epithelial proliferation. As a crucial tryptophan metabolite, I3A promotes intestinal epithelial cell proliferation through the AhR/IL-10/Wnt signaling pathway and upregulates the abundance of probiotics to treat RIE. Microbiota-derived I3A demonstrates potential clinical application value for the treatment of RIE.


Assuntos
Microbioma Gastrointestinal , Indóis , Camundongos Endogâmicos C57BL , Probióticos , Receptores de Hidrocarboneto Arílico , Via de Sinalização Wnt , Animais , Camundongos , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Humanos , Probióticos/administração & dosagem , Probióticos/farmacologia , Receptores de Hidrocarboneto Arílico/metabolismo , Indóis/metabolismo , Indóis/farmacologia , Protetores contra Radiação/farmacologia , Organoides/metabolismo , Lesões por Radiação/metabolismo , Lesões por Radiação/prevenção & controle , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/efeitos da radiação , Intestinos/microbiologia , Intestinos/efeitos da radiação , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética
3.
Microbiome ; 12(1): 89, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745230

RESUMO

BACKGROUND: Non-toxic approaches to enhance radiotherapy outcomes are beneficial, particularly in ageing populations. Based on preclinical findings showing that high-fibre diets sensitised bladder tumours to irradiation by modifying the gut microbiota, along with clinical evidence of prebiotics enhancing anti-cancer immunity, we hypothesised that dietary fibre and its gut microbiota modification can radiosensitise tumours via secretion of metabolites and/or immunomodulation. We investigated the efficacy of high-fibre diets combined with irradiation in immunoproficient C57BL/6 mice bearing bladder cancer flank allografts. RESULT: Psyllium plus inulin significantly decreased tumour size and delayed tumour growth following irradiation compared to 0.2% cellulose and raised intratumoural CD8+ cells. Post-irradiation, tumour control positively correlated with Lachnospiraceae family abundance. Psyllium plus resistant starch radiosensitised the tumours, positively correlating with Bacteroides genus abundance and increased caecal isoferulic acid levels, associated with a favourable response in terms of tumour control. Psyllium plus inulin mitigated the acute radiation injury caused by 14 Gy. Psyllium plus inulin increased caecal acetate, butyrate and propionate levels, and psyllium alone and psyllium plus resistant starch increased acetate levels. Human gut microbiota profiles at the phylum level were generally more like mouse 0.2% cellulose profiles than high fibre profiles. CONCLUSION: These supplements may be useful in combination with radiotherapy in patients with pelvic malignancy. Video Abstract.


Assuntos
Fibras na Dieta , Suplementos Nutricionais , Microbioma Gastrointestinal , Inulina , Camundongos Endogâmicos C57BL , Psyllium , Neoplasias da Bexiga Urinária , Animais , Camundongos , Microbioma Gastrointestinal/efeitos dos fármacos , Inulina/administração & dosagem , Neoplasias da Bexiga Urinária/radioterapia , Neoplasias da Bexiga Urinária/patologia , Humanos , Feminino , Lesões por Radiação/prevenção & controle , Intestinos/microbiologia , Intestinos/efeitos da radiação , Linfócitos T CD8-Positivos
4.
World J Microbiol Biotechnol ; 40(6): 194, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38713319

RESUMO

The development and utilization of probiotics have many environmental benefits when they are used to replace antibiotics in animal production. In this study, intestinal lactic acid bacteria were isolated from the intestines of Cherry Valley ducks. Probiotic lactic acid bacterial strains were screened for antibacterial activity and tolerance to produce a Lactobacillus spp. mixture. The effects of the compound on the growth performance and intestinal flora of Cherry Valley ducks were studied. Based on the results of the antibacterial activity and tolerance tests, the highly active strains Lactobacillus casei 1.2435, L. salivarius L621, and L. salivarius L4 from the intestines of Cherry Valley ducks were selected. The optimum ratio of L. casei 1.2435, L. salivarius L621, and L. salivarius L4 was 1:1:2, the amount of inoculum used was 1%, and the fermentation time was 14 h. In vivo experiments showed that compared with the control group, the relative abundances of intestinal Lactobacillus and Blautia were significantly increased in the experimental group fed the lactobacilli compound (P < 0.05); the relative abundances of Parabacteroides, [Ruminococcus]_torques_group, and Enterococcus were significantly reduced (P < 0.05), and the growth and development of the dominant intestinal flora were promoted in the Cherry Valley ducks. This study will provide more opportunities for Cherry Valley ducks to choose microecological agents for green and healthy breeding.


Assuntos
Patos , Microbioma Gastrointestinal , Intestinos , Lactobacillus , Probióticos , Animais , Probióticos/farmacologia , Patos/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Lactobacillus/isolamento & purificação , Intestinos/microbiologia , Fermentação , Ração Animal , RNA Ribossômico 16S/genética , Antibacterianos/farmacologia
5.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(4): 757-764, 2024 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-38708510

RESUMO

OBJECTIVE: To explore the effect of intestinal nitrates on the growth of Klebsiella pneumoniae and its regulatory mechanisms. METHODS: K. pneumoniae strains with nitrate reductase narG and narZ single or double gene knockout or with NarXL gene knockout were constructed and observed for both aerobic and anaerobic growth in the presence of KNO3 using an automated bacterial growth analyzer and a spectrophotometer, respectively. The mRNA expressions of narG and narZ in K. pneumoniae in anaerobic cultures in the presence of KNO3 and the effect of the binary regulatory system NarXL on their expresisons were detected using qRT-PCR. Electrophoretic mobility shift assays (EMSA) and MST analysis were performed to explore the specific regulatory mechanisms of NarXL in sensing and utilizing nitrates. Competitive experiments were conducted to examine anaerobic growth advantages of narG and narZ gene knockout strains of K. pneumoniae in the presence of KNO3. RESULTS: The presence of KNO3 in anaerobic conditions, but not in aerobic conditions, promoted bacterial growth more effectively in the wild-type K. pneumoniae strain than in the narXL gene knockout strain. In anaerobic conditions, the narXL gene knockout strain showed significantly lowered mRNA expressions of narG and narZ (P < 0.0001). EMSA and MST experiments demonstrated that the NarXL regulator could directly bind to narG and narZ promoter regions. The wild-type K. pneumoniae strain in anaerobic cultures showed significantly increased expressions of narG and narZ mRNAs in the presence of KNO3 (P < 0.01), and narG gene knockout resulted in significantly attenuated anaerobic growth and competitive growth abilities of K. pneumoniae in the presence of KNO3 (P < 0.01). CONCLUSION: The binary regulatory system NarXL of K. pneumoniae can sense changes in intestinal nitrate concentration and directly regulate the expression of nitrate reductase genes narG and narZ to promote bacterial growth.


Assuntos
Klebsiella pneumoniae , Nitrato Redutase , Nitratos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/metabolismo , Klebsiella pneumoniae/efeitos dos fármacos , Nitratos/metabolismo , Nitratos/farmacologia , Nitrato Redutase/metabolismo , Nitrato Redutase/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Intestinos/microbiologia , Regulação Bacteriana da Expressão Gênica , Anaerobiose , Técnicas de Inativação de Genes
6.
Cell Stem Cell ; 31(5): 591-592, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38701755

RESUMO

Recently in Cell Metabolism, Wei et al.1 unveiled a brain-to-gut pathway that conveys psychological stress to intestinal epithelial cells, leading to their dysfunction. This gut-brain axis involves a microbial metabolite, indole-3-acetate (IAA), as a niche signal that hampers mitochondrial respiration to skew intestinal stem cell (ISC) fate.


Assuntos
Células-Tronco , Células-Tronco/metabolismo , Células-Tronco/citologia , Animais , Humanos , Intestinos/citologia , Intestinos/microbiologia , Estresse Fisiológico , Microbioma Gastrointestinal/fisiologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Diferenciação Celular , Mitocôndrias/metabolismo
7.
Nutrients ; 16(9)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38732540

RESUMO

Zinc deficiency affects the physical and intellectual development of school-age children, while studies on the effects on intestinal microbes and metabolites in school-age children have not been reported. School-age children were enrolled to conduct anthropometric measurements and serum zinc and serum inflammatory factors detection, and children were divided into a zinc deficiency group (ZD) and control group (CK) based on the results of serum zinc. Stool samples were collected to conduct metagenome, metabolome, and diversity analysis, and species composition analysis, functional annotation, and correlation analysis were conducted to further explore the function and composition of the gut flora and metabolites of children with zinc deficiency. Beta-diversity analysis revealed a significantly different gut microbial community composition between ZD and CK groups. For instance, the relative abundances of Phocaeicola vulgatus, Alistipes putredinis, Bacteroides uniformis, Phocaeicola sp000434735, and Coprococcus eutactus were more enriched in the ZD group, while probiotic bacteria Bifidobacterium kashiwanohense showed the reverse trend. The functional profile of intestinal flora was also under the influence of zinc deficiency, as reflected by higher levels of various glycoside hydrolases in the ZD group. In addition, saccharin, the pro-inflammatory metabolites, and taurocholic acid, the potential factor inducing intestinal leakage, were higher in the ZD group. In conclusion, zinc deficiency may disturb the gut microbiome community and metabolic function profile of school-age children, potentially affecting human health.


Assuntos
Fezes , Microbioma Gastrointestinal , Zinco , Humanos , Microbioma Gastrointestinal/fisiologia , Zinco/deficiência , Zinco/sangue , Criança , Masculino , Feminino , Fezes/microbiologia , Bactérias/classificação , Bactérias/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Metaboloma , Intestinos/microbiologia
8.
ACS Biomater Sci Eng ; 10(5): 3387-3400, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38656158

RESUMO

Given the worldwide problem posed by enteric pathogens, the discovery of safe and efficient intestinal adjuvants combined with novel antigen delivery techniques is essential to the design of mucosal vaccines. In this work, we designed poly (lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) to codeliver all-trans retinoic acid (atRA), novel antigens, and CpG. To address the insolubility of the intestinal adjuvant atRA, we utilized PLGA to encapsulate atRA and form a "nanocapsid" with polydopamine. By leveraging polydopamine, we adsorbed the water-soluble antigens and the TLR9 agonist CpG onto the NPs' surface, resulting in the pathogen-mimicking PLPCa NPs. In this study, the novel fusion protein (HBf), consisting of the Mycobacterium avium subspecies paratuberculosis antigens HBHA, Ag85B, and Bfra, was coloaded onto the NPs. In vitro, PLPCa NPs were shown to promote the activation and maturation of bone marrow-derived dendritic cells. Additionally, we found that PLPCa NPs created an immune-rich microenvironment at the injection site following intramuscular administration. From the results, the PLPCa NPs induced strong IgA levels in the gut in addition to enhancing powerful systemic immune responses. Consequently, significant declines in the bacterial burden and inflammatory score were noted in PLPCa NPs-treated mice. In summary, PLPCa can serve as a novel and safe vaccine delivery platform against gut pathogens, such as paratuberculosis, capable of activating both systemic and intestinal immunity.


Assuntos
Nanopartículas , Paratuberculose , Animais , Nanopartículas/química , Paratuberculose/imunologia , Paratuberculose/prevenção & controle , Camundongos , Tretinoína/química , Tretinoína/farmacologia , Mycobacterium avium subsp. paratuberculosis/imunologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/química , Células Dendríticas/imunologia , Células Dendríticas/efeitos dos fármacos , Intestinos/imunologia , Intestinos/microbiologia , Camundongos Endogâmicos C57BL , Feminino , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/administração & dosagem , Vacinas Bacterianas/imunologia , Camundongos Endogâmicos BALB C
9.
Food Funct ; 15(9): 4862-4873, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38587236

RESUMO

Intestinal infections are strongly associated with infant mortality, and intestinal immunoglobulin A (IgA) is important to protect infants from intestinal infections after weaning. This study aims to screen probiotics that can promote the production of intestinal IgA after weaning and further explore their potential mechanisms of action. In this study, probiotics promoting intestinal IgA production were screened in weanling mouse models. The results showed that oral administration of Bifidobacterium bifidum (B. bifidum) FL228.1 and Bifidobacterium bifidum (B. bifidum) FL276.1 significantly enhanced IgA levels in the small intestine and upregulated the expression of a proliferation-inducing ligand (APRIL) and its upstream regulatory factor toll-like receptor 4 (TLR4). Furthermore, B. bifidum FL228.1 upregulated the relative abundance of Lactobacillus, while B. bifidum FL276.1 increased the relative abundance of Marvinbryantia and decreased Mucispirillum, further elevating intestinal IgA levels. In summary, B. bifidum FL228.1 and B. bifidum FL276.1 can induce IgA production in the intestinal tract of weanling mice by promoting intestinal APRIL expression and mediating changes in the gut microbiota, thus playing a significant role in enhancing local intestinal immunity in infants.


Assuntos
Bifidobacterium bifidum , Microbioma Gastrointestinal , Imunoglobulina A , Probióticos , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral , Animais , Probióticos/farmacologia , Probióticos/administração & dosagem , Camundongos , Bifidobacterium bifidum/fisiologia , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo , Desmame , Mucosa Intestinal/metabolismo , Mucosa Intestinal/imunologia , Masculino , Intestinos/imunologia , Intestinos/microbiologia , Feminino , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Camundongos Endogâmicos BALB C
10.
World J Gastroenterol ; 30(14): 1963-1967, 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38681124

RESUMO

Digestion and intestinal absorption allow the body to sustain itself and are the emblematic functions of the bowel. On the flip side, functions also arise from its role as an interface with the environment. Indeed, the gut houses microorganisms, collectively known as the gut microbiota, which interact with the host, and is the site of complex immune activities. Its role in human pathology is complex and scientific evidence is progressively elucidating the functions of the gut, especially regarding the pathogenesis of chronic intestinal diseases and inflammatory conditions affecting various organs and systems. This editorial aims to highlight and relate the factors involved in the pathogenesis of intestinal and systemic inflammation.


Assuntos
Microbioma Gastrointestinal , Motilidade Gastrointestinal , Intestinos , Humanos , Microbioma Gastrointestinal/imunologia , Microbioma Gastrointestinal/fisiologia , Motilidade Gastrointestinal/fisiologia , Intestinos/microbiologia , Intestinos/imunologia , Intestinos/fisiopatologia , Inflamação/imunologia , Inflamação/fisiopatologia , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/fisiopatologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Animais
11.
J Microbiol ; 62(3): 167-179, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38630349

RESUMO

The human gut houses a diverse and dynamic microbiome critical for digestion, metabolism, and immune development, exerting profound effects on human health. However, these microorganisms pose a potential threat by breaching the gut barrier, entering host tissues, and triggering infections, uncontrolled inflammation, and even sepsis. The intestinal epithelial cells form the primary defense, acting as a frontline barrier against microbial invasion. Antimicrobial proteins (AMPs), produced by these cells, serve as innate immune effectors that regulate the gut microbiome by directly killing or inhibiting microbes. Abnormal AMP production, whether insufficient or excessive, can disturb the microbiome equilibrium, contributing to various intestinal diseases. This review delves into the complex interactions between AMPs and the gut microbiota and sheds light on the role of AMPs in governing host-microbiota interactions. We discuss the function and mechanisms of action of AMPs, their regulation by the gut microbiota, microbial evasion strategies, and the consequences of AMP dysregulation in disease. Understanding these complex interactions between AMPs and the gut microbiota is crucial for developing strategies to enhance immune responses and combat infections within the gut microbiota. Ongoing research continues to uncover novel aspects of this intricate relationship, deepening our understanding of the factors shaping gut health. This knowledge has the potential to revolutionize therapeutic interventions, offering enhanced treatments for a wide range of gut-related diseases.


Assuntos
Microbioma Gastrointestinal , Microbioma Gastrointestinal/fisiologia , Humanos , Animais , Peptídeos Antimicrobianos/metabolismo , Imunidade Inata , Mucosa Intestinal/microbiologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Bactérias/metabolismo , Intestinos/microbiologia , Intestinos/imunologia
12.
J Microbiol Biotechnol ; 34(4): 828-837, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38668685

RESUMO

Vancomycin (VAN) and metronidazole (MTR) remain the current drugs of choice for the treatment of non-severe Clostridioides difficile infection (CDI); however, while their co-administration has appeared in clinical treatment, the efficacy varies greatly and the mechanism is unknown. In this study, a CDI mouse model was constructed to evaluate the therapeutic effects of VAN and MTR alone or in combination. For a perspective on the intestinal ecology, 16S rRNA amplicon sequencing and non-targeted metabolomics techniques were used to investigate changes in the fecal microbiota and metabolome of mice under the co-administration treatment. As a result, the survival rate of mice under co-administration was not dramatically different compared to that of single antibiotics, and the former caused intestinal tissue hyperplasia and edema. Co-administration also significantly enhanced the activity of amino acid metabolic pathways represented by phenylalanine, arginine, proline, and histidine, decreased the level of deoxycholic acid (DCA), and downregulated the abundance of beneficial microbes, such as Bifidobacterium and Akkermansia. VAN plays a dominant role in microbiota regulation in co-administration. In addition, co-administration reduced or increased the relative abundance of antibiotic-sensitive bacteria, including beneficial and harmful microbes, without a difference. Taken together, there are some risks associated with the co-administration of VAN and MTR, and this combination mode should be used with caution in CDI treatment.


Assuntos
Antibacterianos , Clostridioides difficile , Infecções por Clostridium , Modelos Animais de Doenças , Quimioterapia Combinada , Fezes , Microbioma Gastrointestinal , Metronidazol , RNA Ribossômico 16S , Vancomicina , Animais , Metronidazol/administração & dosagem , Vancomicina/administração & dosagem , Vancomicina/farmacologia , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Clostridioides difficile/efeitos dos fármacos , Clostridioides difficile/genética , RNA Ribossômico 16S/genética , Fezes/microbiologia , Intestinos/microbiologia , Intestinos/efeitos dos fármacos , Masculino , Bactérias/classificação , Bactérias/genética , Bactérias/efeitos dos fármacos , Metaboloma/efeitos dos fármacos
13.
World J Gastroenterol ; 30(15): 2096-2108, 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38681982

RESUMO

Probiotics are live microorganisms exerting beneficial effects on the host's health when administered in adequate amounts. Among the most popular and adequately studied probiotics are bacteria from the families Lactobacillaceae, Bifidobacteriaceae and yeasts. Most of them have been shown, both in vitro and in vivo studies of intestinal inflammation models, to provide favorable results by means of improving the gut microbiota composition, promoting the wound healing process and shaping the immunological responses. Chronic intestinal conditions, such as inflammatory bowel diseases (IBD), are characterized by an imbalance in microbiota composition, with decreased diversity, and by relapsing and persisting inflammation, which may lead to mucosal damage. Although the results of the clinical studies investigating the effect of probiotics on patients with IBD are still controversial, it is without doubt that these microorganisms and their metabolites, now named postbiotics, have a positive influence on both the host's microbiota and the immune system, and ultimately alter the topical tissue microenvironment. This influence is achieved through three axes: (1) By displacement of potential pathogens via competitive exclusion; (2) by offering protection to the host through the secretion of various defensive mediators; and (3) by supplying the host with essential nutrients. We will analyze and discuss almost all the in vitro and in vivo studies of the past 2 years dealing with the possible favorable effects of certain probiotic genus on gut immunological responses, highlighting which species are the most beneficial against intestinal inflammation.


Assuntos
Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Probióticos , Probióticos/uso terapêutico , Probióticos/administração & dosagem , Humanos , Microbioma Gastrointestinal/imunologia , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/terapia , Animais , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Intestinos/imunologia , Intestinos/microbiologia , Disbiose/imunologia
14.
Food Funct ; 15(8): 4503-4514, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38567489

RESUMO

Caloric restriction is an effective means of extending a healthy lifespan. Fasting mimicking diet (FMD) is a growing pattern of caloric restriction. We found that FMD significantly prolonged the lifespan of prematurely aging mice. In naturally aging mice, FMD improved cognitive and intestinal health. Through a series of behavioral experiments, we found that FMD relieved anxiety and enhanced cognition in aged mice. In the intestine, the FMD cycles enhanced the barrier function, reduced senescence markers, and maintained T cell naïve-memory balance in the lamina propria mucosa. To further explore the causes of immune alterations, we examined changes in the stool microbiota using 16S rRNA sequencing. We found that FMD remodeled gut bacterial composition and significantly expanded the abundance of Lactobacillus johnsonii. Our research revealed that FMD has in-depth investigative value as an anti-aging intervention for extending longevity and improving cognition, intestinal function, and gut microbiota composition.


Assuntos
Restrição Calórica , Cognição , Jejum , Microbioma Gastrointestinal , Longevidade , Camundongos Endogâmicos C57BL , Animais , Camundongos , Masculino , Envelhecimento , Intestinos/microbiologia , Dieta
15.
J Hazard Mater ; 470: 134157, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38569337

RESUMO

The wide occurrence of micro- and nanoplastics (MPs/NPs) within aquatic ecosystems has raised increasing concerns regarding their potential effects on aquatic organisms. However, the effects of MPs/NPs on intestinal health and microbiota of fish remain controversial, and there is a lack of comprehensive understanding regarding how the impact of MPs/NPs is influenced by MPs/NPs characteristics and experimental designs. Here, we conducted a global analysis to synthesize the effects of MPs/NPs on 47 variables associated with fish intestinal health and microbiota from 118 studies. We found that MPs/NPs generally exerted obvious adverse effects on intestinal histological structure, permeability, digestive function, immune and oxidative-antioxidative systems. By contrast, MPs/NPs showed slight effects on intestinal microbial variables. Further, we observed that the responses of intestinal variables to MPs/NPs were significantly regulated by MPs/NPs characteristics and experimental designs. For instance, polyvinyl chloride plastics showed higher toxicity to fish gut than polyethylene and polystyrene did. Additionally, larval fish appeared to be more sensitive to MPs/NPs than juvenile fish. Collectively, this study highlights the potential impacts of MPs/NPs on intestinal health and microbiota of fish, and underscores the determinant role of MPs/NPs characteristics and experimental designs in MPs/NPs toxicity.


Assuntos
Peixes , Microbioma Gastrointestinal , Intestinos , Microplásticos , Poluentes Químicos da Água , Animais , Microplásticos/toxicidade , Poluentes Químicos da Água/toxicidade , Intestinos/efeitos dos fármacos , Intestinos/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Nanopartículas/toxicidade , Nanopartículas/química
16.
Mol Biol Rep ; 51(1): 512, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622483

RESUMO

Bacterial enteritis has a substantial role in contributing to a large portion of the global disease burden and serves as a major cause of newborn mortality. Despite advancements gained from current animal and cell models in improving our understanding of pathogens, their widespread application is hindered by apparent drawbacks. Therefore, more precise models are imperatively required to develop more accurate studies on host-pathogen interactions and drug discovery. Since the emergence of intestinal organoids, massive studies utilizing organoids have been conducted to study the pathogenesis of bacterial enteritis, revealing new mechanisms and validating established ones. In this review, we focus on the advancements of several bacterial pathogenesis mechanisms observed in intestinal organoid/enteroid models, exploring the host response and bacterial effectors during the infection process. Finally, we address the features that warrant additional investigation or could be enhanced in existing organoid models in order to guide future research endeavors.


Assuntos
Infecções Bacterianas , Enterite , Animais , Intestinos/microbiologia , Bactérias , Organoides
17.
Nat Commun ; 15(1): 2842, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38565558

RESUMO

Antibiotic-induced dysbiosis is a major risk factor for Clostridioides difficile infection (CDI), and fecal microbiota transplantation (FMT) is recommended for treating CDI. However, the underlying mechanisms remain unclear. Here, we show that Tritrichomonas musculis (T.mu), an integral member of the mouse gut commensal microbiota, reduces CDI-induced intestinal damage by inhibiting neutrophil recruitment and IL-1ß secretion, while promoting Th1 cell differentiation and IFN-γ secretion, which in turn enhances goblet cell production and mucin secretion to protect the intestinal mucosa. T.mu can actively metabolize arginine, not only influencing the host's arginine-ornithine metabolic pathway, but also shaping the metabolic environment for the microbial community in the host's intestinal lumen. This leads to a relatively low ornithine state in the intestinal lumen in C. difficile-infected mice. These changes modulate C. difficile's virulence and the host intestinal immune response, and thus collectively alleviating CDI. These findings strongly suggest interactions between an intestinal commensal eukaryote, a pathogenic bacterium, and the host immune system via inter-related arginine-ornithine metabolism in the regulation of pathogenesis and provide further insights for treating CDI.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Animais , Camundongos , Arginina , Ornitina , Intestinos/microbiologia , Transplante de Microbiota Fecal , Infecções por Clostridium/terapia , Infecções por Clostridium/microbiologia
18.
Gut Microbes ; 16(1): 2340486, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38659243

RESUMO

Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) is a significant threat to public health worldwide. The primary reservoir for CR-Kp is the intestinal tract. There, the bacterium is usually present at low density but can bloom following antibiotic treatment, mostly in hospital settings. The impact of disturbances in the intestinal environment on the fitness, survival, expansion, and drug susceptibility of this pathogen is not well-understood, yet it may be relevant to devise strategies to tackle CR-Kp colonization and infection. Here, we adopted an in vivo model to examine the transcriptional adaptation of a CR-Kp clinical isolate to immune activation in the intestine. We report that as early as 6 hours following host treatment with anti-CD3 antibody, CR-Kp underwent rapid transcriptional changes including downregulation of genes involved in sugar utilization and amino acid biosynthesis and upregulation of genes involved in amino acid uptake and catabolism, antibiotic resistance, and stress response. In agreement with these findings, treatment increased the concentration of oxidative species and amino acids in the mouse intestine. Genes encoding for proteins containing the domain of unknown function (DUF) 1471 were strongly upregulated, however their deletion did not impair CR-Kp fitness in vivo upon immune activation. Transcription factor enrichment analysis identified the global regulator cAMP-Receptor Protein, CRP, as a potential orchestrator of the observed transcriptional signature. In keeping with the recognized role of CRP in regulating utilization of alternative carbon sources, crp deletion in CR-Kp resulted in strongly impaired gut colonization, although this effect was not amplified by immune activation. Thus, following intestinal colonization, which occurs in a CRP-dependent manner, CR-Kp can rapidly respond to immune cues by implementing a well-defined and complex transcriptional program whose direct relevance toward bacterial fitness warrants further investigation. Additional analyses utilizing this model may identify key factors to tackle CR-Kp colonization of the intestine.


Assuntos
Antibacterianos , Intestinos , Infecções por Klebsiella , Klebsiella pneumoniae , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/imunologia , Animais , Camundongos , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/imunologia , Intestinos/microbiologia , Intestinos/imunologia , Antibacterianos/farmacologia , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Regulação Bacteriana da Expressão Gênica , Carbapenêmicos/farmacologia , Camundongos Endogâmicos C57BL , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Feminino , Humanos
19.
Int J Mol Sci ; 25(8)2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38674120

RESUMO

Hematopoietic acute radiation syndrome (H-ARS) involves injury to multiple organ systems following total body irradiation (TBI). Our laboratory demonstrated that captopril, an angiotensin-converting enzyme inhibitor, mitigates H-ARS in Göttingen minipigs, with improved survival and hematopoietic recovery, as well as the suppression of acute inflammation. However, the effects of captopril on the gastrointestinal (GI) system after TBI are not well known. We used a Göttingen minipig H-ARS model to investigate captopril's effects on the GI following TBI (60Co 1.79 or 1.80 Gy, 0.42-0.48 Gy/min), with endpoints at 6 or 35 days. The vehicle or captopril (0.96 mg/kg) was administered orally twice daily for 12 days, starting 4 h post-irradiation. Ilea were harvested for histological, protein, and RNA analyses. TBI increased congestion and mucosa erosion and hemorrhage, which were modulated by captopril. GPX-4 and SLC7A11 were downregulated post-irradiation, consistent with ferroptosis at 6 and 35 days post-irradiation in all groups. Interestingly, p21/waf1 increased at 6 days in vehicle-treated but not captopril-treated animals. An RT-qPCR analysis showed that radiation increased the gene expression of inflammatory cytokines IL1B, TNFA, CCL2, IL18, and CXCL8, and the inflammasome component NLRP3. Captopril suppressed radiation-induced IL1B and TNFA. Rectal microbiome analysis showed that 1 day of captopril treatment with radiation decreased overall diversity, with increased Proteobacteria phyla and Escherichia genera. By 6 days, captopril increased the relative abundance of Enterococcus, previously associated with improved H-ARS survival in mice. Our data suggest that captopril mitigates senescence, some inflammation, and microbiome alterations, but not ferroptosis markers in the intestine following TBI.


Assuntos
Síndrome Aguda da Radiação , Captopril , Modelos Animais de Doenças , Ferroptose , Microbioma Gastrointestinal , Inflamação , Porco Miniatura , Irradiação Corporal Total , Animais , Síndrome Aguda da Radiação/tratamento farmacológico , Suínos , Inflamação/patologia , Captopril/farmacologia , Irradiação Corporal Total/efeitos adversos , Ferroptose/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Intestinos/microbiologia , Intestinos/patologia , Intestinos/efeitos dos fármacos , Intestinos/efeitos da radiação , Masculino , Inibidores da Enzima Conversora de Angiotensina/farmacologia
20.
Nutrients ; 16(8)2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38674840

RESUMO

Throughout infancy, IgA is crucial for maintaining gut mucosal immunity. This study aims to determine whether supplementing newborn mice with eight different strains of Bifidobacterium longum subsp. infantis might regulate their IgA levels. The strains were gavaged to BALB/C female (n = 8) and male (n = 8) dams at 1-3 weeks old. Eight strains of B. longum subsp. infantis had strain-specific effects in the regulation of intestinal mucosal barriers. B6MNI, I4MI, and I10TI can increase the colonic IgA level in females and males. I8TI can increase the colonic IgA level in males. B6MNI was also able to significantly increase the colonic sIgA level in females. B6MNI, I4MI, I8TI, and I10TI regulated colonic and Peyer's patch IgA synthesis genes but had no significant effect on IgA synthesis pathway genes in the jejunum and ileum. Moreover, the variety of sIgA-coated bacteria in male mice was changed by I4MI, I5TI, I8TI, and B6MNI. These strains also can decrease the relative abundance of Escherichia coli. These results indicate that B. longum subsp. infantis can promote IgA levels but show strain specificity. Different dietary habits with different strains of Bifidobacterium may have varying effects on IgA levels when supplemented in early infancy.


Assuntos
Bifidobacterium longum subspecies infantis , Bifidobacterium , Imunoglobulina A , Mucosa Intestinal , Camundongos Endogâmicos BALB C , Probióticos , Animais , Feminino , Masculino , Imunoglobulina A/metabolismo , Camundongos , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/metabolismo , Probióticos/administração & dosagem , Microbioma Gastrointestinal , Animais Recém-Nascidos , Intestinos/microbiologia , Intestinos/imunologia , Imunidade nas Mucosas , Especificidade da Espécie , Colo/microbiologia , Colo/imunologia , Colo/metabolismo , Imunoglobulina A Secretora/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...