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1.
mSystems ; 9(3): e0071523, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38363147

RESUMO

Bifidobacterium longum subsp. infantis is a representative and dominant species in the infant gut and is considered a beneficial microbe. This organism displays multiple adaptations to thrive in the infant gut, regarded as a model for human milk oligosaccharides (HMOs) utilization. These carbohydrates are abundant in breast milk and include different molecules based on lactose. They contain fucose, sialic acid, and N-acetylglucosamine. Bifidobacterium metabolism is complex, and a systems view of relevant metabolic pathways and exchange metabolites during HMO consumption is missing. To address this limitation, a refined genome-scale network reconstruction of this bacterium is presented using a previous reconstruction of B. infantis ATCC 15967 as a template. The latter was expanded based on an extensive revision of genome annotations, current literature, and transcriptomic data integration. The metabolic reconstruction (iLR578) accounted for 578 genes, 1,047 reactions, and 924 metabolites. Starting from this reconstruction, we built context-specific genome-scale metabolic models using RNA-seq data from cultures growing in lactose and three HMOs. The models revealed notable differences in HMO metabolism depending on the functional characteristics of the substrates. Particularly, fucosyl-lactose showed a divergent metabolism due to a fucose moiety. High yields of lactate and acetate were predicted under growth rate maximization in all conditions, whereas formate, ethanol, and 1,2-propanediol were substantially lower. Similar results were also obtained under near-optimal growth on each substrate when varying the empirically observed acetate-to-lactate production ratio. Model predictions displayed reasonable agreement between central carbon metabolism fluxes and expression data across all conditions. Flux coupling analysis revealed additional connections between succinate exchange and arginine and sulfate metabolism and a strong coupling between central carbon reactions and adenine metabolism. More importantly, specific networks of coupled reactions under each carbon source were derived and analyzed. Overall, the presented network reconstruction constitutes a valuable platform for probing the metabolism of this prominent infant gut bifidobacteria.IMPORTANCEThis work presents a detailed reconstruction of the metabolism of Bifidobacterium longum subsp. infantis, a prominent member of the infant gut microbiome, providing a systems view of its metabolism of human milk oligosaccharides.


Assuntos
Fucose , Leite Humano , Lactente , Feminino , Humanos , Leite Humano/química , Fucose/análise , Lactose/análise , Oligossacarídeos/análise , Bifidobacterium/genética , Bifidobacterium longum subspecies infantis/metabolismo , Acetatos/análise , Carbono/análise , Lactatos/análise
2.
Int J Pharm ; 652: 123804, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38220120

RESUMO

Microencapsulation of probiotics is a main technique employed to improve cell survival in gastrointestinal tract (GIT). The present study investigated the impact of utilizing proteins i.e. Whey Protein Isolates (WPI), Pea Protein Isolates (PPI) or (WPI + PPI) complex based microbeads as encapsulating agents on the encapsulation efficiency (EE), diameter, morphology along with the survival and viability of Bifidobacterium infantis ATCC 15697. Results revealed that WPI + PPI combination had the highest EE% of the probiotics up to 94.09 % and the smoothest surface with less visible holes. WPI based beads revealed lower EE% and smaller size than PPI based ones. In addition, WPI based beads showed rough surface with visible signs of cracks, while PPI beads showed dense surfaces with pores and depressions. In contrast, the combination of the two proteins resulted in compact and smooth beads with less visible pores/wrinkles. The survival in gastrointestinal tract (GIT) was observed through TNO in-vitro gastrointestinal model (TIM-1) and results illustrated that all microbeads shrank in gastric phase while swelled in intestinal phase. In addition, in-vitro survival rate of free cells was very low in gastric phase (18.2 %) and intestinal phase (27.5 %). The free cells lost their viability after 28 days of storage (2.66 CFU/mL) with a maximum log reduction of 6.76, while all the encapsulated probiotic showed more than 106-7 log CFU/g viable cell. It was concluded that encapsulation improved the viability of probiotics in GIT and utilization of WPI + PPI in combination provided better protection to probiotics.


Assuntos
Bifidobacterium longum subspecies infantis , Probióticos , Microesferas , Trato Gastrointestinal , Polissacarídeos , Proteínas do Soro do Leite , Viabilidade Microbiana
3.
Gut Microbes ; 16(1): 2304160, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38235736

RESUMO

Precision engineering of the gut microbiome holds promise as an effective therapeutic approach for diseases associated with a disruption in this microbial community. Engrafting a live biotherapeutic product (LBP) in a predictable, controllable manner is key to the consistent success of this approach and has remained a challenge for most LBPs under development. We recently demonstrated high-level engraftment of Bifidobacterium longum subsp. infantis (B. infantis) in adults when co-dosed with a specific prebiotic, human milk oligosaccharides (HMO). Here, we present a cellular kinetic-pharmacodynamic approach, analogous to pharmacokinetic-pharmacodynamic-based analyses of small molecule- and biologic-based drugs, to establish how HMO controls expansion, abundance, and metabolic output of B. infantis in a human microbiota-based model in gnotobiotic mice. Our data demonstrate that the HMO dose controls steady-state abundance of B. infantis in the microbiome, and that B. infantis together with HMO impacts gut metabolite levels in a targeted, HMO-dependent manner. We also found that HMO creates a privileged niche for B. infantis expansion across a 5-log range of bacterial inocula. These results demonstrate remarkable control of both B. infantis levels and the microbiome community metabolic outputs using this synbiotic approach, and pave the way for precision engineering of desirable microbes and metabolites to treat a range of diseases.


Assuntos
Bifidobacterium , Microbioma Gastrointestinal , Humanos , Animais , Camundongos , Leite Humano/metabolismo , Oligossacarídeos/metabolismo , Bifidobacterium longum subspecies infantis
4.
J Dairy Sci ; 107(1): 91-104, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37678788

RESUMO

The milk fat globule membrane (MFGM) can protect probiotic bacteria from bile stress. However, its potential mechanism has not been reported. In this study, the viability, morphology and gene transcriptional response of Bifidobacterium longum ssp. infantis ATCC 15697 (BI_15697) stressed by bile salts with or without MFGM were investigated. It was shown that MFGM alleviated the reduction in BI_15697 population induced by 0.2% porcine bile stress and restored the population to the control levels. MFGM ameliorated the shrunken, fragmented appearance and irregular morphology of BI_15697 and maintained cell integrity disrupted by bile stress. RNA-sequencing results showed that MFGM increased transport of glucose and raffinose and decreased that of branched-chain amino acids (BCAA) in the presence of bile salts. MFGM stimulated the expression of genes involved in the synthesis of raffinose in galactose metabolism and the metabolism of BCAA, suggesting that MFGM stimulated the accumulation of raffinose and BCAA in the presence of bile. In addition, MFGM stimulated the expression of 2 bile efflux transporters under bile stress. Together, the multifactorial response helps BI_15697 excrete bile salts and maintain cellular integrity in response to bile stress. This study proposes a mechanism for the protection of BI_15697 against bile salt stress by MFGM, thereby providing a molecular basis for its application in incorporation of probiotics.


Assuntos
Bifidobacterium longum subspecies infantis , Bile , Glicoproteínas , Animais , Suínos , Rafinose , Glicolipídeos , Gotículas Lipídicas , Ácidos e Sais Biliares
5.
Gut Microbes ; 16(1): 2290344, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38116652

RESUMO

Bifidobacterium longum subsp. infantis is a prevalent member of the gut microbiota of breastfed infants. In this study, the effects of human breastmilk-derived B.longum subsp. infantis CCFM1269 on bone formation in developing BALB/c mice were investigated. Newborn female and male mice were assigned to control group (administered saline), CCFM11269 group (administered B. longum subsp. infantis CCFM1269, 1 × 109 CFU/mouse/day) and I5TI group (administered B. longum subsp. infantis I5TI, 1 × 109 CFU/mouse/day) from 1-week-old to 3-, 4- and 5-week old. B. longum subsp. infantis I5TI served as a negative control in this study. The results demonstrated that B. longum subsp. infantis CCFM1269 promoted bone formation in growing mice by modulating the composition of the gut microbiota and metabolites. The expression of genes and proteins in the PI3K/AKT pathway was stimulated by B. longum subsp. infantis CCFM1269 through the GH/IGF-1 axis in growing mice. This finding suggests B. longum subsp. infantis CCFM1269 may be useful for modulating bone metabolism during growth.


Assuntos
Bifidobacterium , Microbioma Gastrointestinal , Leite Humano , Osteogênese , Animais , Feminino , Humanos , Lactente , Masculino , Camundongos , Bifidobacterium longum subspecies infantis , Leite Humano/microbiologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo
6.
Sci Adv ; 9(49): eade1370, 2023 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-38064556

RESUMO

Bacille Calmette-Guerin (BCG) vaccine can elicit good TH1 responses in neonates. We hypothesized that the pioneer gut microbiota affects vaccine T cell responses. Infants who are HIV exposed but uninfected (iHEU) display an altered immunity to vaccination. BCG-specific immune responses were analyzed at 7 weeks of age in iHEU, and responses were categorized as high or low. Bifidobacterium longum subsp. infantis was enriched in the stools of high responders, while Bacteroides thetaiotaomicron was enriched in low responders at time of BCG vaccination. Neonatal germ-free or SPF mice orally gavaged with live B. infantis exhibited significantly higher BCG-specific T cells compared with pups gavaged with B. thetaiotaomicron. B. infantis and B. thetaiotaomicron differentially affected stool metabolome and colonic transcriptome. Human colonic epithelial cells stimulated with B. infantis induced a unique gene expression profile versus B. thetaiotaomicron. We thus identified a causal role of B. infantis in early-life antigen-specific immunity.


Assuntos
Bifidobacterium longum subspecies infantis , Microbioma Gastrointestinal , Humanos , Lactente , Camundongos , Animais , Vacina BCG , Linfócitos T , Fezes/microbiologia
7.
BMC Complement Med Ther ; 23(1): 367, 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37853370

RESUMO

INTRODUCTION: Infants who are born from mothers with HIV (infants who are HIV exposed but uninfected; iHEU) are at higher risk of morbidity and display multiple immune alterations compared to infants who are HIV-unexposed (iHU). Easily implementable strategies to improve immunity of iHEU, and possibly subsequent clinical health outcomes, are needed. iHEU have altered gut microbiome composition and bifidobacterial depletion, and relative abundance of Bifidobacterium infantis has been associated with immune ontogeny, including humoral and cellular vaccine responses. Therefore, we will assess microbiological and immunological phenotypes and clinical outcomes in a randomized, double-blinded trial of B. infantis Rosell®-33 versus placebo given during the first month of life in South African iHEU. METHODS: This is a parallel, randomised, controlled trial. Two-hundred breastfed iHEU will be enrolled from the Khayelitsha Site B Midwife Obstetric Unit in Cape Town, South Africa and 1:1 randomised to receive 8 × 109 CFU B. infantis Rosell®-33 daily or placebo for the first 4 weeks of life, starting on day 1-3 of life. Infants will be followed over 36 weeks with extensive collection of meta-data and samples. Primary outcomes include gut microbiome composition and diversity, intestinal inflammation and microbial translocation and cellular vaccine responses. Additional outcomes include biological (e.g. gut metabolome and T cell phenotypes) and clinical (e.g. growth and morbidity) outcome measures. DISCUSSION: The results of this trial will provide evidence whether B. infantis supplementation during early life could improve health outcomes for iHEU. ETHICS AND DISSEMINATION: Approval for this study has been obtained from the ethics committees at the University of Cape Town (HREC Ref 697/2022) and Seattle Children's Research Institute (STUDY00003679). TRIAL REGISTRATION: Pan African Clinical Trials Registry Identifier: PACTR202301748714019. TRIALS: gov: NCT05923333. PROTOCOL VERSION: Version 1.8, dated 18 July 2023.


Assuntos
Infecções por HIV , Vacinas , Feminino , Humanos , Lactente , Gravidez , Bifidobacterium longum subspecies infantis , Suplementos Nutricionais , Infecções por HIV/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , África do Sul
8.
Nutrients ; 15(19)2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37836387

RESUMO

Obesity has emerged as one of the most prevalent chronic diseases worldwide. Our study was conducted to investigate the anti-obese potential of novel probiotic Bifidobacterium longum subsp. infantis FB3-14 (FB3-14) and the underlying molecular mechanisms in high-fat diet (HFD)-fed mice. The results demonstrated that an 8-week FB3-14 intervention significantly suppressed the HFD-induced body and fat weight gain and abnormal alterations of the serum lipid parameter, restoring the levels of cholesterol (4.29 mmol/L) and low-density lipoprotein cholesterol (3.42 mmol/L). FB3-14 treatment also attenuated adipocyte expansion, hepatic injury, and low-grade systemic inflammation and restored the expressions of lipid-metabolism-related genes, including Hsl, Leptin, and Adiponectin. Furthermore, FB3-14 was observed to reduce the Firmicutes/Bacteroidetes ratio in obese mice; increase the abundance of Akkermansia muciniphila, unclassified_Muribaculaceae, Lachnospiraceae_NK4A136_group, and Bifidobacterim; and upregulate G protein-coupled receptor41 associated with higher levels of butyric acid. These results indicate the protective effectiveness of FB3-14 in HFD-driven obesity and gut microbiota disorders, highlighting the promising potential of FB3-14 as a functional nutrition supplement.


Assuntos
Microbioma Gastrointestinal , Camundongos , Animais , Dieta Hiperlipídica/efeitos adversos , Obesidade/metabolismo , Bifidobacterium longum subspecies infantis , Butiratos/farmacologia , Colesterol/farmacologia , Bacteroidetes , Camundongos Endogâmicos C57BL
9.
Appl Environ Microbiol ; 89(9): e0097923, 2023 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-37681950

RESUMO

Bifidobacterium is the dominant genus, particularly in the intestinal tract niche of healthy breast-fed infants, and many of these strains have been proven to elicit positive effects on infant development. In addition to its effective antimicrobial activity against detrimental microorganisms, it helps to improve the intestinal microbiota balance. The isolation and identification of bacteriocins from Bifidobacterium have been limited since the mid-1980s, leading to an underestimation of its ability for bacteriocin production. Here, we employed a silicon-based search strategy to mine 354 putative bacteriocin gene clusters (BGCs), most of which have never been reported, from the genomes of 759 Bifidobacterium strains distributed across 9 species. Consistent with previous reports, most Bifidobacterium strains did not carry or carry only a single BGC; however, Bifidobacterium longum subsp. infantis, in contrast to other Bifidobacterium species, carried numerous BGCs, including lanthipeptides, lasso peptides, thiopeptides, and class IId bacteriocins. The antimicrobial activity of the crude bacteriocins and transcription analysis confirmed its potential for bacteriocin biosynthesis. Additionally, we investigated the association of bacteriocins with the phylogenetic positions of their homologs from other genera and niches. In conclusion, this study re-examines a few Bifidobacterium species traditionally regarded as a poor source of bacteriocins. These bacteriocin genes impart a competitive advantage to Bifidobacterium in colonizing the infant intestinal tract. IMPORTANCE Development of the human gut microbiota commences from birth, with bifidobacteria being among the first colonizers of the newborn intestinal tract and dominating it for a considerable period. To date, the genetic basis for the successful adaptation of bifidobacteria to this particular niche remains unclear since studies have mainly focused on glycoside hydrolase and adhesion-related genes. Bacteriocins are competitive factors that help producers maintain colonization advantages without destroying the niche balance; however, they have rarely been reported in Bifidobacterium. The advancement in sequencing methods and bacteriocin databases enables the use of a silicon-based search strategy for the comprehensive and rapid re-evaluation of the bacteriocin distribution of Bifidobacterium. Our study revealed that B. infantis carries abundant bacteriocin biosynthetic gene clusters for the first time, presenting new evidence regarding the competitive interactions of Bifidobacterium in the infant intestinal tract.


Assuntos
Anti-Infecciosos , Bacteriocinas , Lactente , Recém-Nascido , Criança , Feminino , Humanos , Bifidobacterium/genética , Bacteriocinas/genética , Filogenia , Silício , Bifidobacterium longum subspecies infantis , Família Multigênica
10.
Nutrients ; 15(18)2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37764787

RESUMO

We investigated the effects of two dosing regimens of two multi-strain probiotic products on the gut microbiota of breastfed infants, including the transfer of the dosed strains and clinical outcomes. In forty-seven dyads, infants were either exposed through maternal intake (MS) of Lactobacillus acidophilus LA-5, Bifidobacterium animalis subsp. lactis BB-12, Lacticaseibacillus rhamnosus LGG, and Bifidobacterium longum subsp. infantis Bifin02 from gestational week thirty-three until four weeks after birth (n = 24) or dosed directly (IS) with the same strains except for LA-5 starting within 24 h after birth until day 28 (n = 23). Infant stool samples were collected on day 0, 14, 28, and 42 after birth. Gastrointestinal symptoms were assessed by parents using an electronic diary. Microbiota composition was determined using 16S rRNA sequencing, and strain recovery was analyzed by qPCR. Notably, 100% of the IS infants were colonized with Bifin02 after 14 days as opposed to only 25% of the MS infants. Mean stool frequency was significantly lower in IS infants compared to MS infants and IS infants had softer stools on day 14, 28, and 42. A significantly steeper slope of progression of inconsolable crying and fussing was observed in MS infants compared to IS infants. In conclusion, direct infant seeding induced a faster increase in fecal bifidobacteria abundancy and Bifin02 recovery compared to dosed through the maternal intake.


Assuntos
Bifidobacterium animalis , Microbiota , Probióticos , Feminino , Humanos , Lactente , Aleitamento Materno , RNA Ribossômico 16S/genética , Lactobacillus acidophilus , Fezes/microbiologia , Bifidobacterium longum subspecies infantis/genética
11.
Gut Microbes ; 15(2): 2244721, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37609905

RESUMO

Bifidobacterium longum subsp. infantis (B. infantis) utilizes oligosaccharides secreted in human milk as a carbohydrate source. These human milk oligosaccharides (HMOs) integrate the nitrogenous residue N-acetylglucosamine (NAG), although HMO nitrogen utilization has not been described to date. Herein, we characterize the B. infantis nitrogen utilization phenotype on two NAG-containing HMO species, LNT and LNnT. This was characterized through in vitro growth kinetics, incorporation of isotopically labeled NAG nitrogen into the proteome, as well as modulation of intracellular 2-oxoglutarate levels while utilizing HMO nitrogen. Further support is provided by comparative transcriptomics and proteomics that identified global regulatory networks deployed during HMO nitrogen utilization. The aggregate data demonstrate that B. infantis strains utilize HMO nitrogen with the potential to significantly impact fundamental and clinical studies, as well as enable applications.


Assuntos
Bifidobacterium longum subspecies infantis , Microbioma Gastrointestinal , Humanos , Acetilglucosamina , Leite Humano , Oligossacarídeos , Nitrogênio
12.
Pediatr Res ; 94(6): 1887-1905, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37460707

RESUMO

BACKGROUND: Bifidobacterium infantis has special abilities to utilise human milk oligosaccharides. Hence we hypothesised that probiotic supplements containing B. infantis may confer greater benefits to preterm infants than probiotic supplements without B. infantis. METHODS: A systematic review with meta-analysis was conducted according to standard guidelines. We selected RCTs evaluating probiotics compared to placebo or no treatment in preterm and/or low birth weight infants. Probiotic effects on Necrotizing Enterocolitis (NEC), Late Onset Sepsis (LOS) and Mortality were analysed separately for RCTs in which the supplemented probiotic product contained B. infantis and those that did not contain B. infantis. RESULTS: 67 RCTs were included (n = 14,606), of which 16 used probiotics containing B. infantis (Subgroup A) and 51 RCTs did not (Subgroup B) Meta-analysis of all RCTs indicated that probiotics reduced the risk of NEC, LOS, and mortality. The subgroup meta-analysis demonstrated greater reduction in the incidence of NEC in subgroup A than subgroup B [(relative risk in subgroup A: 0.38; 95% CI, 0.27-0.55) versus (0.67; 95% CI, 0.55-0.81) in subgroup B; p value for subgroup difference: 0.01]. CONCLUSIONS: These results provide indirect evidence that probiotic supplements that include B. infantis may be more beneficial for preterm infants. Well-designed RCTs are necessary to confirm these findings. IMPACT: Evidence is emerging that beneficial effects of probiotics are species and strain specific. This systematic review analyses if B. infantis supplementation provides an advantage to preterm infants. This is the first systematic review evaluating the effects of probiotics containing B. infantis in preterm infants. The results of this systematic review provides indirect evidence that probiotics that include B. infantis may be more beneficial for preterm infants. These results will help in guiding future research and clinical practice for using B. infantis as a probiotic in preterm infants.


Assuntos
Enterocolite Necrosante , Probióticos , Sepse , Lactente , Recém-Nascido , Humanos , Recém-Nascido Prematuro , Bifidobacterium longum subspecies infantis , Probióticos/uso terapêutico , Suplementos Nutricionais , Recém-Nascido de Baixo Peso , Enterocolite Necrosante/prevenção & controle , Sepse/prevenção & controle , Sepse/microbiologia
13.
Int J Mol Sci ; 24(14)2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37511481

RESUMO

Previous studies have found that Bifidobacterium infantis-mediated herpes simplex virus-TK/ganciclovir (BF-TK/GCV) reduces the expression of VEGF and CD146, implying tumor metastasis inhibition. However, the mechanism by which BF-TK/GCV inhibits tumor metastasis is not fully studied. Here, we comprehensively identified and quantified protein expression profiling for the first time in gastric cancer (GC) cells MKN-45 upon BF-TK/GCV treatment using quantitative proteomics. A total of 159 and 72 differential expression proteins (DEPs) were significantly changed in the BF-TK/GCV/BF-TK and BF-TK/GCV/BF/GCV comparative analysis. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis enriched some metastasis-related pathways such as gap junction and cell adhesion molecules pathways. Moreover, the transwell assay proved that BF-TK/GCV inhibited the invasion and migration of tumor cells. Furthermore, immunohistochemistry (IHC) demonstrated that BF-TK/GCV reduced the expression of HIF-1α, mTOR, NF-κB1-p105, VCAM1, MMP13, CXCL12, ATG16, and CEBPB, which were associated with tumor metastasis. In summary, BF-TK/GCV inhibited tumor metastasis, which deepened and expanded the understanding of the antitumor mechanism of BF-TK/GCV.


Assuntos
Ganciclovir , Neoplasias Gástricas , Camundongos , Animais , Ganciclovir/farmacologia , Ganciclovir/uso terapêutico , Simplexvirus/genética , Simplexvirus/metabolismo , Bifidobacterium longum subspecies infantis/metabolismo , Terapia Genética , Modelos Animais de Doenças , Neoplasias Gástricas/terapia , Timidina Quinase/genética , Antivirais/farmacologia
14.
Nutrients ; 15(11)2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37299550

RESUMO

Necrotizing enterocolitis (NEC) is the leading cause of death caused by gastrointestinal disease in preterm infants. Major risk factors include prematurity, formula feeding, and gut microbial colonization. Microbes have been linked to NEC, yet there is no evidence of causal species, and select probiotics have been shown to reduce NEC incidence in infants. In this study, we evaluated the effect of the probiotic Bifidobacterium longum subsp. infantis (BL. infantis), alone and in combination with a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on the microbiome, and the incidence of NEC in preterm piglets fed an infant formula diet. We studied 50 preterm piglets randomized between 5 treatments: (1) Preterm infant formula, (2) Donor human milk (DHM), (3) Infant formula + 3'SL, (4) Infant formula + BL. infantis, and (5) Infant formula and BL. infantis + 3'SL. NEC incidence and severity were assessed through the evaluation of tissue from all the segments of the GI tract. The gut microbiota composition was assessed both daily and terminally through 16S and whole-genome sequencing (WGS) of rectal stool samples and intestinal contents. Dietary BL. infantis and 3'SL supplementation had no effect, yet DHM significantly reduced the incidence of NEC. The abundance of BL. infantis in the gut contents negatively correlated with disease severity. Clostridium sensu stricto 1 and Clostridium perfringens were significantly more abundant in NEC and positively correlated with disease severity. Our results suggest that pre- and probiotics are not sufficient for protection from NEC in an exclusively formula-based diet. The results highlight the differences in microbial species positively associated with both diet and NEC incidence.


Assuntos
Enterocolite Necrosante , Microbioma Gastrointestinal , Probióticos , Animais , Humanos , Bifidobacterium longum subspecies infantis , Enterocolite Necrosante/epidemiologia , Enterocolite Necrosante/prevenção & controle , Enterocolite Necrosante/etiologia , Incidência , Leite Humano , Suínos
15.
Int J Mol Sci ; 24(9)2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37175970

RESUMO

Exposure to long-term chronic unpredictable mild stress (CUMS) can cause redox imbalance and inflammation, which may affect the integrity of the gut barrier. The present study was conducted to investigate the effects of a probiotics bacterium mixture, including Clostridium butyricum (C. butyricum) and Bifidobacterium infantis (B. infantis), on the intestinal homeostasis in rats exposed to multiple low-intensity stressors for 28 days. The mechanism of CUMS-induced altered intestinal homeostasis was evaluated by focusing on the nuclear factor-E2-related factor-2 (Nrf-2) pathway. In contrast to the CUMS group, probiotic mixture supplementation significantly (p < 0.01) reversed the stress-induced elevated corticosterone level, protein and lipid oxidation, and increased enzymatic and non-enzymatic antioxidant levels, as well as upregulated Nrf-2/HO-1 pathway. Probiotics supplementation further significantly (p < 0.01) decreased the CUMS-induced inflammation, altered T-lymphocyte levels, and suppressed the protein expression of nuclear factor kappa B (NF-κB) in rat intestines. Improvement in histological changes and intestinal barrier integrity further validate the beneficial effects of probiotic mixtures on CUMS-induced altered intestinal morphology. In conclusion, our results suggest that the combination of C. butyricum and B. infantis significantly attenuated CUMS-induced oxidative stress, inflammation, and T-lymphocyte modulation by upregulating Nrf-2/HO-1 signaling and inhibiting NF-κB expression in rat intestine.


Assuntos
Clostridium butyricum , Probióticos , Ratos , Animais , NF-kappa B/metabolismo , Bifidobacterium longum subspecies infantis/metabolismo , Transdução de Sinais , Inflamação , Probióticos/farmacologia , Probióticos/uso terapêutico
16.
Nutrients ; 15(6)2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36986131

RESUMO

Bifidobacteria are important intestinal bacteria that provide a variety of health benefits in infants. We investigated the efficacy and safety of Bifidobacterium longum subsp. infantis (B. infantis) M-63 in healthy infants in a double-blind, randomized, placebo-controlled trial. Healthy term infants were given B. infantis M-63 (n = 56; 1 × 109 CFU/day) or placebo (n = 54) from postnatal age ≤ 7 days to 3 months. Fecal samples were collected, and fecal microbiota, stool pH, short-chain fatty acids, and immune substances were analyzed. Supplementation with B. infantis M-63 significantly increased the relative abundance of Bifidobacterium compared with the placebo group, with a positive correlation with the frequency of breastfeeding. Supplementation with B. infantis M-63 led to decreased stool pH and increased levels of acetic acid and IgA in the stool at 1 month of age compared with the placebo group. There was a decreased frequency of defecation and watery stools in the probiotic group. No adverse events related to test foods were observed. These results indicate that early supplementation with B. infantis M-63 is well tolerated and contributes to the development of Bifidobacterium-predominant gut microbiota during a critical developmental phase in term infants.


Assuntos
Microbioma Gastrointestinal , Probióticos , Feminino , Humanos , Lactente , Recém-Nascido , Bifidobacterium , Bifidobacterium longum subspecies infantis , Aleitamento Materno , Fezes/microbiologia
17.
Mol Nutr Food Res ; 67(11): e2200851, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36938958

RESUMO

SCOPE: Fucosylated human milk oligosaccharides (fHMOs) are metabolized by Bifidobacterium infantis and promote syntrophic interactions between microbiota that colonize the infant gut. The role of fHMO structure on syntrophic interactions and net microbiome function is not yet fully understood. METHODS AND RESULTS: Metabolite production and microbial populations are tracked during mono- and co-culture fermentations of 2'fucosyllactose (2'FL) and difucosyllactose (DFL) by two B. infantis strains and Eubacterium hallii. This is also conducted in an in vitro modeled microbiome supplemented by B. infantis and/or E. hallii. Metabolites are quantified by high performance liquid chromatography. Total B. infantis and E. hallii populations are quantified through qRT-PCR and community composition through 16S amplicon sequencing. Differential metabolism of 2'FL and DFL by B. infantis strains gives rise to strain- and fHMO structure-specific syntrophy with E. hallii. Within the modeled microbial community, fHMO structure does not strongly alter metabolite production in aggregate, potentially due to functional redundancy within the modeled community. In contrast, community composition is dependent on fHMO structure. CONCLUSION: Whereas short chain fatty acid production is not significantly altered by the specific fHMO structure introduced to the modeled community, specific fHMO structure influences the composition of the gut microbiome.


Assuntos
Microbioma Gastrointestinal , Leite Humano , Humanos , Lactente , Leite Humano/química , Bifidobacterium longum subspecies infantis/metabolismo , Oligossacarídeos/metabolismo
18.
Nat Commun ; 14(1): 1349, 2023 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-36906612

RESUMO

Preterm infants with very low birthweight are at serious risk for necrotizing enterocolitis. To functionally analyse the principles of three successful preventive NEC regimens, we characterize fecal samples of 55 infants (<1500 g, n = 383, female = 22) longitudinally (two weeks) with respect to gut microbiome profiles (bacteria, archaea, fungi, viruses; targeted 16S rRNA gene sequencing and shotgun metagenomics), microbial function, virulence factors, antibiotic resistances and metabolic profiles, including human milk oligosaccharides (HMOs) and short-chain fatty acids (German Registry of Clinical Trials, No.: DRKS00009290). Regimens including probiotic Bifidobacterium longum subsp. infantis NCDO 2203 supplementation affect microbiome development globally, pointing toward the genomic potential to convert HMOs. Engraftment of NCDO 2203 is associated with a substantial reduction of microbiome-associated antibiotic resistance as compared to regimens using probiotic Lactobacillus rhamnosus LCR 35 or no supplementation. Crucially, the beneficial effects of Bifidobacterium longum subsp. infantis NCDO 2203 supplementation depends on simultaneous feeding with HMOs. We demonstrate that preventive regimens have the highest impact on development and maturation of the gastrointestinal microbiome, enabling the establishment of a resilient microbial ecosystem that reduces pathogenic threats in at-risk preterm infants.


Assuntos
Microbioma Gastrointestinal , Recém-Nascido Prematuro , Lactente , Recém-Nascido , Humanos , Feminino , RNA Ribossômico 16S/genética , Ecossistema , Intestinos , Fezes/microbiologia , Bifidobacterium longum subspecies infantis/genética
19.
Gut Microbes ; 15(1): 2192546, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36967532

RESUMO

Human milk guides the structure and function of microbial commensal communities that colonize the nursing infant gut. Indigestible molecules dissolved in human milk establish a microbiome often dominated by bifidobacteria capable of utilizing these substrates. Interestingly, urea accounts for ~15% of total human milk nitrogen, representing a potential reservoir for microbiota that may be salvaged for critical metabolic operations during lactation and neonatal development. Accordingly, B. infantis strains are competent for urea nitrogen utilization, constituting a previously hypothetical phenotype in commensal bacteria hosted by humans. Urease gene expression, downstream nitrogen metabolic pathways, and enzymatic activity are induced during urea utilization to yield elevated ammonia concentrations. Moreover, biosynthetic networks relevant to infant nutrition and development are transcriptionally responsive to urea utilization including branched chain and other essential amino acids. Importantly, isotopically labeled urea nitrogen is broadly distributed throughout the expressed B. infantis proteome. This incisively demonstrates that the previously inaccessible urea nitrogen is incorporated into microbial products available for infant host utilization. In aggregate, B. infantis possesses the requisite phenotypic foundation to participate in human milk urea nitrogen recycling within its infant host and thus may be a key contributor to nitrogen homeostasis early in life.


Assuntos
Microbioma Gastrointestinal , Leite Humano , Recém-Nascido , Feminino , Lactente , Humanos , Leite Humano/química , Ureia/análise , Ureia/metabolismo , Oligossacarídeos/metabolismo , Bifidobacterium longum subspecies infantis
20.
Anaerobe ; 80: 102713, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36754140

RESUMO

Prophylactic administration of oral probiotics is associated with significant reductions in the morbidity and mortality of necrotising enterocolitis in preterm infants. We document the first case of Bifidobacterium longum subsp. infantis sub-clinical bacteraemia, in an extremely low birth weight preterm infant, since introduction of routine probiotic treatment at the Norfolk and Norwich University Hospital 10 years ago. Whole genome comparisons confirmed the isolated strain likely originated from the probiotic product.


Assuntos
Bacteriemia , Probióticos , Lactente , Recém-Nascido , Humanos , Recém-Nascido Prematuro , Bifidobacterium/genética , Bacteriemia/diagnóstico , Bifidobacterium longum subspecies infantis
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