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Probiotics are widely prescribed for prevention of antibiotics-associated dysbiosis and related adverse effects. However, probiotic impact on post-antibiotic reconstitution of the gut mucosal host-microbiome niche remains elusive. We invasively examined the effects of multi-strain probiotics or autologous fecal microbiome transplantation (aFMT) on post-antibiotic reconstitution of the murine and human mucosal microbiome niche. Contrary to homeostasis, antibiotic perturbation enhanced probiotics colonization in the human mucosa but only mildly improved colonization in mice. Compared to spontaneous post-antibiotic recovery, probiotics induced a markedly delayed and persistently incomplete indigenous stool/mucosal microbiome reconstitution and host transcriptome recovery toward homeostatic configuration, while aFMT induced a rapid and near-complete recovery within days of administration. In vitro, Lactobacillus-secreted soluble factors contributed to probiotics-induced microbiome inhibition. Collectively, potential post-antibiotic probiotic benefits may be offset by a compromised gut mucosal recovery, highlighting a need of developing aFMT or personalized probiotic approaches achieving mucosal protection without compromising microbiome recolonization in the antibiotics-perturbed host.
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Antibacterianos/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Probióticos/administración & dosificación , Adolescente , Adulto , Anciano , Animales , Trasplante de Microbiota Fecal , Heces/microbiología , Femenino , Humanos , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/microbiología , Lactobacillus/efectos de los fármacos , Lactobacillus/genética , Lactobacillus/aislamiento & purificación , Lactococcus/genética , Lactococcus/aislamiento & purificación , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , ARN Ribosómico 16S/análisis , ARN Ribosómico 16S/genética , ARN Ribosómico 16S/metabolismo , Adulto JovenRESUMEN
Homeostasis of the gut microbiota critically influences host health and aging. Developing genetically engineered probiotics holds great promise as a new therapeutic paradigm to promote healthy aging. Here, through screening 3,983 Escherichia coli mutants, we discovered that 29 bacterial genes, when deleted, increase longevity in the host Caenorhabditis elegans. A dozen of these bacterial mutants also protect the host from age-related progression of tumor growth and amyloid-beta accumulation. Mechanistically, we discovered that five bacterial mutants promote longevity through increased secretion of the polysaccharide colanic acid (CA), which regulates mitochondrial dynamics and unfolded protein response (UPRmt) in the host. Purified CA polymers are sufficient to promote longevity via ATFS-1, the host UPRmt-responsive transcription factor. Furthermore, the mitochondrial changes and longevity effects induced by CA are conserved across different species. Together, our results identified molecular targets for developing pro-longevity microbes and a bacterial metabolite acting on host mitochondria to promote longevity.
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Caenorhabditis elegans/microbiología , Escherichia coli/genética , Longevidad , Envejecimiento/metabolismo , Péptidos beta-Amiloides/metabolismo , Animales , Carga Bacteriana , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Escherichia coli/metabolismo , Eliminación de Gen , Estudio de Asociación del Genoma Completo , Dinámicas Mitocondriales , Modelos Animales , Polisacáridos/metabolismo , Factores de Transcripción/metabolismo , Respuesta de Proteína DesplegadaRESUMEN
Nutritional supplementation with probiotics can prevent pathologic bone loss. Here we examined the impact of supplementation with Lactobacillus rhamnosus GG (LGG) on bone homeostasis in eugonadic young mice. Micro-computed tomography revealed that LGG increased trabecular bone volume in mice, which was due to increased bone formation. Butyrate produced in the gut following LGG ingestion, or butyrate fed directly to germ-free mice, induced the expansion of intestinal and bone marrow (BM) regulatory T (Treg) cells. Interaction of BM CD8+ T cells with Treg cells resulted in increased secretion of Wnt10b, a bone anabolic Wnt ligand. Mechanistically, Treg cells promoted the assembly of a NFAT1-SMAD3 transcription complex in CD8+ cells, which drove expression of Wnt10b. Reducing Treg cell numbers, or reconstitution of TCRß-/- mice with CD8+ T cells from Wnt10b-/- mice, prevented butyrate-induced bone formation and bone mass acquisition. Thus, butyrate concentrations regulate bone anabolism via Treg cell-mediated regulation of CD8+ T cell Wnt10b production.
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Butiratos/farmacología , Osteogénesis/efectos de los fármacos , Linfocitos T Reguladores/metabolismo , Proteínas Wnt/metabolismo , Animales , Butiratos/metabolismo , Linfocitos T CD8-positivos/citología , Linfocitos T CD8-positivos/metabolismo , Comunicación Celular , Proliferación Celular/efectos de los fármacos , Femenino , Lacticaseibacillus rhamnosus/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Probióticos/administración & dosificación , Probióticos/metabolismo , Linfocitos T Reguladores/citología , Proteínas Wnt/genéticaRESUMEN
Beneficial bacteria remain largely unexplored. Lacking systematic methods, understanding probiotic community traits becomes challenging, leading to various conclusions about their probiotic effects among different publications. We developed language model-based metaProbiotics to rapidly detect probiotic bins from metagenomes, demonstrating superior performance in simulated benchmark datasets. Testing on gut metagenomes from probiotic-treated individuals, it revealed the probioticity of intervention strains-derived bins and other probiotic-associated bins beyond the training data, such as a plasmid-like bin. Analyses of these bins revealed various probiotic mechanisms and bai operon as probiotic Ruminococcaceae's potential marker. In different health-disease cohorts, these bins were more common in healthy individuals, signifying their probiotic role, but relevant health predictions based on the abundance profiles of these bins faced cross-disease challenges. To better understand the heterogeneous nature of probiotics, we used metaProbiotics to construct a comprehensive probiotic genome set from global gut metagenomic data. Module analysis of this set shows that diseased individuals often lack certain probiotic gene modules, with significant variation of the missing modules across different diseases. Additionally, different gene modules on the same probiotic have heterogeneous effects on various diseases. We thus believe that gene function integrity of the probiotic community is more crucial in maintaining gut homeostasis than merely increasing specific gene abundance, and adding probiotics indiscriminately might not boost health. We expect that the innovative language model-based metaProbiotics tool will promote novel probiotic discovery using large-scale metagenomic data and facilitate systematic research on bacterial probiotic effects. The metaProbiotics program can be freely downloaded at https://github.com/zhenchengfang/metaProbiotics.
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Metagenoma , Probióticos , Humanos , Algoritmos , Metagenómica/métodos , Bacterias/genética , LenguajeRESUMEN
With the increasing prevalence of age-related chronic diseases burdening healthcare systems, there is a pressing need for innovative management strategies. Our study focuses on the gut microbiota, essential for metabolic, nutritional, and immune functions, which undergoes significant changes with aging. These changes can impair intestinal function, leading to altered microbial diversity and composition that potentially influence health outcomes and disease progression. Using advanced metagenomic sequencing, we explore the potential of personalized probiotic supplements in 297 older adults by analyzing their gut microbiota. We identified distinctive Lactobacillus and Bifidobacterium signatures in the gut microbiota of older adults, revealing probiotic patterns associated with various population characteristics, microbial compositions, cognitive functions, and neuroimaging results. These insights suggest that tailored probiotic supplements, designed to match individual probiotic profile, could offer an innovative method for addressing age-related diseases and functional declines. Our findings enhance the existing evidence base for probiotic use among older adults, highlighting the opportunity to create more targeted and effective probiotic strategies. However, additional research is required to validate our results and further assess the impact of precision probiotics on aging populations. Future studies should employ longitudinal designs and larger cohorts to conclusively demonstrate the benefits of tailored probiotic treatments.
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Envejecimiento , Suplementos Dietéticos , Microbioma Gastrointestinal , Probióticos , Probióticos/uso terapéutico , Probióticos/administración & dosificación , Humanos , Anciano , Femenino , Masculino , Anciano de 80 o más Años , Persona de Mediana Edad , Lactobacillus/genética , Metagenómica/métodos , BifidobacteriumRESUMEN
Gut microbiota has been shown to systemically shape the immunological landscape, modulate homeostasis and play a role in both health and disease. Dysbiosis of gut microbiota promotes inflammation and contributes to the pathogenesis of several major disorders in gastrointestinal tract, metabolic, neurological and respiratory diseases. Much effort is now focused on understanding host-microbes interactions and new microbiota-targeted therapies are deeply investigated as a means to restore health or prevent disease. This review details the immunoregulatory role of the gut microbiota in health and disease and discusses the most recent strategies in manipulating individual patient's microbiota for the management and prevention of inflammatory conditions.
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Microbioma Gastrointestinal , Microbiota , Humanos , Disbiosis/terapia , Inflamación/terapia , Tracto GastrointestinalRESUMEN
Inflammatory bowel disease (IBD) is a spectrum of autoimmune diseases affecting the gastrointestinal tract characterized by a relapsing and remitting course of gut mucosal inflammation. Disease flares can be difficult to predict, and the current practice of IBD disease activity surveillance through endoscopy is invasive and requires medical expertise. Recent advancements in synthetic biology raise the possibility that symbiotic microbes can be engineered to selectively detect disease biomarkers used in current clinical practice. Here, we introduce an engineered probiotic capable of detecting the clinical gold standard IBD biomarker, calprotectin, with sensitivity and specificity in IBD patients. Specifically, we identified a bacterial promoter in the probiotic strain Escherichia coli Nissle 1917 (EcN) which exhibits a specific expression increase in the presence of calprotectin. Using murine models of colitis, we show that the reporter signal is activated in vivo during transit of the GI tract following oral delivery. Furthermore, our engineered probiotic can successfully discriminate human patients with active IBD from those in remission and without IBD using patient stool samples, where the intensity of reporter signal quantitatively tracks with clinical laboratory-measured levels of calprotectin. Our pilot study sets the stage for probiotics that can be engineered to detect fecal calprotectin for precise noninvasive disease activity monitoring in IBD patients.
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Colitis , Enfermedades Inflamatorias del Intestino , Probióticos , Humanos , Animales , Ratones , Complejo de Antígeno L1 de Leucocito/metabolismo , Proyectos Piloto , Enfermedades Inflamatorias del Intestino/metabolismo , Sensibilidad y Especificidad , Heces , Biomarcadores/metabolismoRESUMEN
SUMMARYThe gut microbiota is a major factor contributing to the regulation of energy homeostasis and has been linked to both excessive body weight and accumulation of fat mass (i.e., overweight, obesity) or body weight loss, weakness, muscle atrophy, and fat depletion (i.e., cachexia). These syndromes are characterized by multiple metabolic dysfunctions including abnormal regulation of food reward and intake, energy storage, and low-grade inflammation. Given the increasing worldwide prevalence of obesity, cachexia, and associated metabolic disorders, novel therapeutic strategies are needed. Among the different mechanisms explaining how the gut microbiota is capable of influencing host metabolism and energy balance, numerous studies have investigated the complex interactions existing between nutrition, gut microbes, and their metabolites. In this review, we discuss how gut microbes and different microbiota-derived metabolites regulate host metabolism. We describe the role of the gut barrier function in the onset of inflammation in this context. We explore the importance of the gut-to-brain axis in the regulation of energy homeostasis and glucose metabolism but also the key role played by the liver. Finally, we present specific key examples of how using targeted approaches such as prebiotics and probiotics might affect specific metabolites, their signaling pathways, and their interactions with the host and reflect on the challenges to move from bench to bedside.
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Brevibacillus laterosporus is a strain of probiotic bacteria that has been widely used in pest control, cash crop, and other production areas. However, few studies have been conducted on its use as a feed additive in animals. Therefore, the probiotic potential of B. laterosporus PBC01 was evaluated by characterizing hydrophobicity, auto-aggregation activity, bile salt and simulated gastrointestinal fluid tolerance, bienzymatic, and antibacterial activity. Antibiotic susceptibility, hemolysis assays, and supplemental feeding of mice were also performed to evaluate safety features. Our results showed that B. laterosporus PBC01 had moderate hydrophobicity, high auto-agglutination ability. Meanwhile, B. laterosporus PBC01 had good tolerance to bile salt and simulated gastrointestinal fluid. It had the ability to secrete protease, cellulase, and to inhibit various pathogens. In addition, B. laterosporus PBC01 was sensitive to many antibiotics, and did not produce hemolysin. In the safety assessment of mice, it did not cause any deaths, nor did it affect the cell components of blood, antioxidant capacity, and reproductive health. The study indicated the great probiotic characteristics and safety of B. laterosporus PBC01. This may provide a theoretical basis for the clinical application and development of probiotic-based feed additives.
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Bacillus , Brevibacillus , Animales , Ratones , Antibacterianos/farmacología , Ácidos y Sales BiliaresRESUMEN
BACKGROUND: We examined components of systemic and intestinal renin-angiotensin system on gut barrier permeability, glucose homeostasis, systemic inflammation, and progression of diabetic retinopathy (DR) in human subjects and mice with type 1 diabetes (T1D). METHODS: T1D individual with (n=18) and without (n=20) DR and controls (n=34) were examined for changes in gut-regulated components of the immune system, gut leakage markers (FABP2 [fatty acid binding protein 2] and peptidoglycan), and Ang II (angiotensin II); Akita mice were orally administered a Lactobacillus paracasei (LP) probiotic expressing humanized ACE2 (angiotensin-converting enzyme 2) protein (LP-ACE2) as either a prevention or an intervention. Akita mice with genetic overexpression of humanAce2 by small intestine epithelial cells (Vil-Cre.hAce2KI-Akita) were similarly examined. After 9 months of T1D, circulatory, enteral, and ocular end points were assessed. RESULTS: T1D subjects exhibit elevations in gut-derived circulating immune cells (ILC1 cells) and higher gut leakage markers, which were positively correlated with plasma Ang II and DR severity. The LP-ACE2 prevention cohort and genetic overexpression of intestinal ACE2 preserved barrier integrity, reduced inflammatory response, improved hyperglycemia, and delayed development of DR. Improvements in glucose homeostasis were due to intestinal MasR activation, resulting in a GSK-3ß (glycogen synthase kinase-3 beta)/c-Myc (cellular myelocytomatosis oncogene)-mediated decrease in intestinal glucose transporter expression. In the LP-ACE2 intervention cohort, gut barrier integrity was improved and DR reversed, but no improvement in hyperglycemia was observed. These data support that the beneficial effects of LP-ACE2 on DR are due to the action of ACE2, not improved glucose homeostasis. CONCLUSIONS: Dysregulated systemic and intestinal renin-angiotensin system was associated with worsening gut barrier permeability, gut-derived immune cell activation, systemic inflammation, and progression of DR in human subjects. In Akita mice, maintaining intestinal ACE2 expression prevented and reversed DR, emphasizing the multifaceted role of the intestinal renin-angiotensin system in diabetes and DR.
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Diabetes Mellitus Tipo 1 , Retinopatía Diabética , Hiperglucemia , Animales , Humanos , Ratones , Enzima Convertidora de Angiotensina 2/metabolismo , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/metabolismo , Retinopatía Diabética/prevención & control , Glucosa/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Hiperglucemia/complicaciones , Inflamación/metabolismo , Intestino Delgado , Fragmentos de Péptidos/metabolismo , Peptidil-Dipeptidasa A/genética , Sistema Renina-Angiotensina/fisiologíaRESUMEN
Streptococcus pneumoniae (Spn) is the predominant pathogen responsible for community-acquired pneumonia (CAP) in children under five years old, and it can induce over 17% of pregnant women. However, no more effective measures exist to prevent infection induced by Spn in these two special populations. The beneficial microbes can antagonize Spn and provide new targets for preventing pneumococcal infections. This study used 16S rRNA gene sequencing and targeted metabolomics to evaluate the role of the Bacillus aerolatus CX253 (CX253) in alleviating Spn infection. Additionally, the colonization of CX253 was observed in nose, trachea, and lung by using confocal laser scanning microscopy and fluorescent labeling techniques. Compared with the model group, the expression level of interleukin-1ß was dropped 1.81-fold and 2.22-fold, and interleukin-6 was decreased 2.39-fold and 1.84-fold. The express of tumor necrosis factor-α was down 2.30-fold and 3.84-fold in prevention group of childhood and pregnant rats, respectively. The 16S rRNA sequencing results showed that CX253 administration alone significantly increased the abundance of Lactobacillus, Limosilactobacillus, and Prevotella in the gut of childhood and pregnant rats. Furthermore, the CX253 increased propionate in the gut of childhood rats and increased propionate and butyrate in the gut of pregnant rats to inhibit pulmonary inflammation. In summary, CX253 attenuated Spn-induced inflammation by regulating the gut microbiota and SCFAs. The research provides valuable information for the prevention of pneumonia.
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Bacillus , Microbioma Gastrointestinal , Inflamación , Streptococcus pneumoniae , Animales , Femenino , Embarazo , Microbioma Gastrointestinal/efectos de los fármacos , Ratas , Inflamación/metabolismo , Inflamación/patología , Inflamación/microbiología , Bacillus/metabolismo , Humanos , ARN Ribosómico 16S/genética , ARN Ribosómico 16S/metabolismo , Ratas Sprague-Dawley , Masculino , Interleucina-1beta/metabolismo , Interleucina-1beta/genética , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/genética , Interleucina-6/metabolismo , Interleucina-6/genética , Pulmón/microbiología , Pulmón/patología , Pulmón/metabolismo , Probióticos/farmacologíaRESUMEN
Bifidobacterium is a commensal bacterial genus ubiquitous in the human gastrointestinal tract, which is associated with a range of health benefits. The advent of CRISPR-based genome editing technologies provides opportunities to investigate the genetics of important bacteria and transcend the lack of genetic tools in bifidobacteria to study the basis for their health-promoting attributes. Here, we repurpose the endogenous type I-G CRISPR-Cas system and adopt an exogenous CRISPR base editor for genome engineering in B. animalis subsp. lactis, demonstrating that both genomic and epigenetic contexts drive editing outcomes across strains. We reprogrammed the endogenous type I-G system to screen for naturally occurring large deletions up to 27 kb and to generate a 500-bp deletion in tetW to abolish tetracycline resistance. A CRISPR-cytosine base editor was optimized to install Câ¢G-to-Tâ¢A amber mutations to resensitize multiple B. lactis strains to tetracycline. Remarkably, we uncovered epigenetic patterns that are distributed unevenly among B. lactis strains, despite their genomic homogeneity, that may contribute to editing efficiency variability. Insights were also expanded to Bifidobacterium longum subsp. infantis to emphasize the broad relevance of these findings. This study highlights the need to develop individualized CRISPR-based genome engineering approaches for distinct bacterial strains and opens avenues for engineering of next generation probiotics.
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Bifidobacterium , Sistemas CRISPR-Cas , Edición Génica , Probióticos , Bifidobacterium/genética , Edición Génica/métodos , Genoma Bacteriano/genética , Genómica , HumanosRESUMEN
Antibiotic therapeutics to combat intestinal pathogen infections often exacerbate microbiota dysbiosis and impair mucosal barrier functions. Probiotics are promising strategies, because they inhibit pathogen colonization and improve intestinal microbiota imbalance. Nevertheless, their limited targeting ability and susceptibility to oxidative stress have hindered their therapeutic potential. To tackle these challenges, Ces3 is synthesized by in situ growth of CeO2 nanozymes with positive charges on probiotic spores, facilitating electrostatic interactions with negatively charged pathogens and possessing a high reactive oxygen species (ROS) scavenging activity. Importantly, Ces3 can resist the harsh environment of the gastrointestinal tract. In mice with S. Typhimurium-infected acute gastroenteritis, Ces3 shows potent anti-S. Typhimurium activity, thereby alleviating the dissemination of S. Typhimurium into other organs. Additionally, owing to its O2 deprivation capacity, Ces3 promotes the proliferation of anaerobic probiotics, reshaping a healthy intestinal microbiota. This work demonstrates the promise of combining antibacterial, anti-inflammatory, and O2 content regulation properties for acute gastroenteritis therapy.
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Gastroenteritis , Probióticos , Animales , Ratones , Intestinos , Gastroenteritis/tratamiento farmacológico , Gastroenteritis/microbiología , Antibacterianos/uso terapéutico , Probióticos/uso terapéutico , EsporasRESUMEN
While oral probiotics show promise in treating inflammatory bowel disease, the primary challenge lies in sustaining their activity and retention within the inflamed gastrointestinal environment. In this work, we develop an engineered probiotic platform that is armed with biocatalytic and inflamed colon-targeting nanocoatings for multipronged management of IBD. Notably, we achieve the in situ growth of artificial nanocatalysts on probiotics through a bioinspired mineralization strategy. The resulting ferrihydrite nanostructures anchored on bacteria exhibit robust catalase-like activity across a broad pH range, effectively scavenging ROS to alleviate inflammation. The further envelopment with fucoidan-based shields confers probiotics with additional inflamed colon-targeting functions. Upon oral administration, the engineered probiotics display markedly improved viability and colonization within the inflamed intestine, and they further elicit boosted prophylactic and therapeutic efficacy against colitis through the synergistic interplay of nanocatalysis-based immunomodulation and probiotics-mediated microbiota reshaping. The robust and multifunctional probiotic platforms offer great potential for the comprehensive management of gastrointestinal disorders.
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Oral administration of probiotics orchestrates the balance between intestinal microbes and the immune response. However, effective delivery and in situ colonization are limited by the harsh environment of the gastrointestinal tract. Herein, we provide a microfluidics-derived encapsulation strategy to address this problem. A novel synergistic delivery system composed of EcN Nissle 1917 and prebiotics, including alginate sodium and inulin gel, for treating inflammatory bowel disease and colitis-associated colorectal cancer is proposed. We demonstrated that EcN@AN microparticles yielded promising gastrointestinal resistance for on-demand probiotic delivery and colon-retentive capability. EcN@AN microparticles efficiently ameliorated intestinal inflammation and modulated the gut microbiome in experimental colitis. Moreover, the prebiotic composition of EcN@AN enhanced the fermentation of relative short-chain fatty acid metabolites, a kind of postbiotics, to exert anti-inflammatory and tumor-suppressive effects in murine models. This microfluidcis-based approach for the coordinated delivery of probiotics and prebiotics may have broad implications for gastrointestinal bacteriotherapy applications.
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Colitis , Probióticos , Animales , Ratones , Prebióticos , Microfluídica , Colitis/terapia , Probióticos/uso terapéutico , InmunidadRESUMEN
OBJECTIVE: Probiotic Lactococcus lactis is known to confer health benefits to humans. Here, we aimed to investigate the role of L. lactis in colorectal cancer (CRC). DESIGN: L. lactis abundance was evaluated in patients with CRC (n=489) and healthy individuals (n=536). L. lactis was isolated from healthy human stools with verification by whole genome sequencing. The effect of L. lactis on CRC tumourigenesis was assessed in transgenic Apc Min/+ mice and carcinogen-induced CRC mice. Faecal microbiota was profiled by metagenomic sequencing. Candidate proteins were characterised by nano liquid chromatography-mass spectrometry. Biological function of L. lactis conditioned medium (HkyuLL 10-CM) and functional protein was studied in human CRC cells, patient-derived organoids and xenograft mice. RESULTS: Faecal L. lactis was depleted in patients with CRC. A new L. lactis strain was isolated from human stools and nomenclated as HkyuLL 10. HkyuLL 10 supplementation suppressed CRC tumourigenesis in Apc Min/+ mice, and this tumour-suppressing effect was confirmed in mice with carcinogen-induced CRC. Microbiota profiling revealed probiotic enrichment including Lactobacillus johnsonii in HkyuLL 10-treated mice. HkyuLL 10-CM significantly abrogated the growth of human CRC cells and patient-derived organoids. Such protective effect was attributed to HkyuLL 10-secreted proteins, and we identified that α-mannosidase was the functional protein. The antitumourigenic effect of α-mannosidase was demonstrated in human CRC cells and organoids, and its supplementation significantly reduced tumour growth in xenograft mice. CONCLUSION: HkyuLL 10 suppresses CRC tumourigenesis in mice through restoring gut microbiota and secreting functional protein α-mannosidase. HkyuLL 10 administration may serve as a prophylactic measure against CRC.
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Carcinogénesis , Neoplasias Colorrectales , Heces , Microbioma Gastrointestinal , Lactococcus lactis , Probióticos , alfa-Manosidasa , Animales , Neoplasias Colorrectales/microbiología , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/prevención & control , Microbioma Gastrointestinal/fisiología , Humanos , Ratones , Probióticos/uso terapéutico , Heces/microbiología , alfa-Manosidasa/metabolismo , Ratones Transgénicos , Femenino , MasculinoRESUMEN
Bifidobacteria are early colonizers of the human neonatal gut and provide multiple health benefits to the infant, including inhibiting the growth of enteropathogens and modulating the immune system. Certain Bifidobacterium species prevail in the gut of breastfed infants due to the ability of these microorganisms to selectively forage glycans present in human milk, specifically human milk oligosaccharides (HMOs) and N-linked glycans. Therefore, these carbohydrates serve as promising prebiotic dietary supplements to stimulate the growth of bifidobacteria in the guts of children suffering from impaired gut microbiota development. However, the rational formulation of milk glycan-based prebiotics requires a detailed understanding of how bifidobacteria metabolize these carbohydrates. Accumulating biochemical and genomic data suggest that HMO and N-glycan assimilation abilities vary remarkably within the Bifidobacterium genus, both at the species and strain levels. This review focuses on the delineation and genome-based comparative analysis of differences in respective biochemical pathways, transport systems, and associated transcriptional regulatory networks, providing a foundation for genomics-based projection of milk glycan utilization capabilities across a rapidly growing number of sequenced bifidobacterial genomes and metagenomic datasets. This analysis also highlights remaining knowledge gaps and suggests directions for future studies to optimize the formulation of milk-glycan-based prebiotics that target bifidobacteria.
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Bifidobacterium , Prebióticos , Lactante , Recién Nacido , Niño , Humanos , Bifidobacterium/genética , Bifidobacterium/metabolismo , Prebióticos/análisis , Leche Humana/química , Leche Humana/metabolismo , Polisacáridos/metabolismo , Carbohidratos/análisis , GenómicaRESUMEN
Neonatal respiratory distress syndrome (NRDS) is one of the most severe respiratory disorders in preterm infants (PTIs) due to immature lung development. To delineate the serum metabolic alterations and gut microbiota variations in NRDS and assess their implications on neonatal development, we enrolled 13 NRDS neonates and 12 PTIs and collected fecal and serum specimens after birth. Longitudinal fecal sampling was conducted weekly for a month in NRDS neonates. NRDS neonates were characterized by notably reduced gestational ages and birth weights and a higher rate of asphyxia at birth relative to PTIs. Early postnatal disturbances in tryptophan metabolism were evident in the NRDS group, concomitant with elevated relative abundance of Haemophilus, Fusicatenibacter, and Vibrio. Integrative multiomics analyses revealed an inverse relationship between tryptophan concentrations and Blautia abundance. At one-week old, NRDS neonates exhibited cortisol regulation anomalies and augmented hepatic catabolism. Sequential microbial profiling revealed distinct gut microbiota evolution in NRDS subjects, characterized by a general reduction in potentially pathogenic bacteria. The acute perinatal stress of NRDS leads to mitochondrial compromise, hormonal imbalance, and delayed gut microbiota evolution. Despite the short duration of NRDS, its impact on neonatal development is significant and requires extended attention.
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Heces , Microbioma Gastrointestinal , Recien Nacido Prematuro , Síndrome de Dificultad Respiratoria del Recién Nacido , Humanos , Recién Nacido , Síndrome de Dificultad Respiratoria del Recién Nacido/microbiología , Síndrome de Dificultad Respiratoria del Recién Nacido/metabolismo , Heces/microbiología , Femenino , Masculino , Edad Gestacional , Triptófano/metabolismo , Triptófano/sangre , Hidrocortisona/sangreRESUMEN
This study aimed to examine the impact of SCD Probiotics supplementation on liver biomolecule content and histological changes during a 30-day intermittent fasting (IF) program in 24-month-old male Sprague-Dawley rats. Rats underwent 18-h daily fasting and received 1 × 108 CFU of SCD Probiotics daily. Liver tissue biomolecules were analysed using FTIR Spectroscopy, LDA, and SVM techniques, while histopathological evaluations used Haematoxylin and eosin and Masson trichrome-stained tissues. Blood samples were collected for biochemical analysis. Gross alterations in the quantity of biomolecules were observed with individual or combined treatments. LDA and SVM analyses demonstrated a high accuracy in differentiating control and treated groups. The combination treatments led to the most significant reduction in cholesterol ester (1740 cm-1 ) and improved protein phosphorylation (A1239 /A2955 and A1080 /A1545 ) and carbonylation (A1740 /A1545 ). Individually, IF and SCD Probiotics were more effective in enhancing membrane dynamics (Bw2922 /Bw2955 ). In treated groups, histological evaluations showed decreased hepatocyte degeneration, lymphocyticinfiltration, steatosis and fibrosis. Serum ALP, LDH and albumin levels significantly increased in the SCD Probiotics and combined treatment groups. This study offers valuable insights into the potential mechanisms behind the beneficial effects of IF and SCD Probiotics on liver biomolecule content, contributing to the development of personalized nutrition and health strategies.
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Hepatopatías , Probióticos , Ratas , Masculino , Animales , Ratas Sprague-Dawley , Ayuno Intermitente , Hígado/patología , Hepatopatías/patología , FibrosisRESUMEN
This study aimed to explore the impact of SCD Probiotics supplementation on biomolecule profiles and histopathology of ileum and colon tissues during a 30-day intermittent fasting (IF) program. Male Sprague-Dawley rats, aged 24 months, underwent 18-h daily fasting and received 3 mL (1 × 108 CFU) of SCD Probiotics. The differences in biomolecule profiles were determined using FTIR Spectroscopy and two machine learning techniques, Linear Discriminant Analysis (LDA) and Support Vector Machine (SVM), which showed significant differences with high accuracy rates. Spectrochemical bands indicating alterations in lipid, protein and nucleic acid profiles in both tissues. The most notable changes were observed in the group subjected to both IF and SCD Probiotics, particularly in the colon. Both interventions, individually and in combination, decreased protein carbonylation levels. SCD Probiotics exerted a more substantial impact on membrane dynamics than IF alone. Additionally, both IF and SCD Probiotics were found to have protective effects on intestinal structure and stability by reducing mast cell density and levels of TNF-α and NF-κB expression in ileum and colon tissues, thus potentially mitigating age-related intestinal damage and inflammation. Furthermore, our results illustrated that while IF and SCD Probiotics individually instigate unique changes in ileum and colon tissues, their combined application yielded more substantial benefits. This study provides evidence for the synergistic potential of IF and SCD Probiotics in combating age-related intestinal alterations.