The immune-modulatory effects of Bifidobacterium in IBD. 

The immune-modulatory effects of Bifidobacterium in IBD. 

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The gut-associated microbiota is essential for multiple physiological processes, including immune development. Acquisition of our initial pioneer microbial communities, including the dominant early life genus Bifidobacterium, occurs at a critical period of immune maturation and programming. Bifidobacteria are resident microbiota members throughout...

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... the cell type, species of animal, model used, and human cohort supplemented also affect immune responses generated [39]. Currently, most mechanistic studies have focused on inflammatory bowel disease (IBD) (Figure 2), allergy, and infection models, reporting bifidobacterial-associated modulation of specific immune cells and their outputs. There are also some limited reports highlighting immune receptor-ligand interactions and downstream signalling events Although further studies are required to test this hypothesis, this figure illustrates the potential correlation between bifidobacteria and immune cell maturation in early life. ...

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... 11 Bifidobacteria have anti-inflammatory properties and have been found to be lower in human patients with IBD. 36 In our study, no alteration in Bifidobacteria was observed. An increase in mucosaassociated Fusobacterium spp and Bacteroides spp in ileal biopsies of cats with LGITL and an increase in mucosa-associated Fusobacterium spp in colonic biopsies of cats with LGITL compared with that of cats with LPE have been previously described. ...
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OBJECTIVE To evaluate the fecal bacterial microbiota at the time of diagnosis (T0) and after 1 month of therapy (T1) in cats diagnosed with lymphoplasmacytic enteritis (LPE) or cats with low-grade intestinal T-cell lymphoma (LGITL) and to compare these findings with those of healthy cats. ANIMALS 5 healthy cats, 13 cats with LPE, and 7 cats with LGITL were prospectively enrolled between June 2020 and June 2021. METHODS Fecal samples were collected at T0 and T1, and DNA was extracted for 16S ribosomal amplicon sequencing. Alpha diversity and beta diversity were computed. The taxonomic assignment was performed using sequences from the Silva v138 formatted reference database. Differential abundant taxa were selected in each taxonomic level, with the P value adjusted < .05, as the cut-off. RESULTS No significant differences in alpha and beta diversity were found either at T0 or T1 between healthy and diseased cats or between cats with LPE and LGITL. Beta-diversity analysis showed an increase in the Fusobacteriaceae family in cats with LGITL at T0, compared to cats with LPE. Regardless of histological diagnosis, several microbiota differences were found at T0 based on serum cobalamin levels. CLINICAL RELEVANCE Fecal samples were successfully used to characterize the bacteriome of the intestinal tract in cats by 16S rRNA gene sequencing. However, results highlighted that the metagenomic evaluation was not useful to discriminate between LPE and LGITL nor to predict the therapeutic response in this study population.
... Among its diverse microbial inhabitants, Bifidobacteria have gained considerable attention for their potential immunomodulatory effects. These beneficial bacteria have demonstrated the ability to interact with the host's immune system, influencing its homeostasis [4,5]. ...
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The interaction between the gut microbiota and the host can influence the host’s immune system. Bifidobacterium, a commensal genus of gut bacteria, seems to have positive effects on host health. Our previous clinical research showed that B. longum subsp. longum BB536 enhanced innate and adaptive immune responses in elderly individuals with a lower grade of immunity, but the immunomodulatory mechanism is still unclear. In this study, dendritic cell (DC) surface markers in peripheral blood mononuclear cells isolated from healthy individuals were evaluated through coculture with heat-killed BB536. DC markers, innate immune activity and cytokine levels in plasma were also evaluated by a randomized, double-blind, placebo-controlled, parallel-group study (UMIN000045564) with 4 weeks of continuous live BB536 intake. BB536 significantly increased the expression of CD86 and HLA-DR on plasmacytoid DCs (pDCs) in vitro. Compared to placebo (n = 48), a significant increase in the expression of CD86 on peripheral pDCs was detected at week 4 of live BB536 intake (n = 49; 1 × 1010 CFU/day). Furthermore, coculture with hk-BB536 significantly increased the IFNγ expression level and demonstrated trends of increased IFNα1 and IFNβ expression. These findings suggest that consumption of BB536 has potential immunomodulatory effects on healthy individuals through the activation of peripheral pDCs.
... 8 In adults, presence of Bifidobacterium is also associated with "health", and particular strains have potential roles in the reduction of serum cholesterol, alleviation of lactose intolerance, and treatment of inflammatory bowel diseases, acute diarrhea, colorectal cancer, and other intestinal infections. 7,9 Sources of Beneficial Bacteria or "Probiotics" ...
... 10 Indeed, Lactobacillus buchneri P2, isolated from pickled juice, has probiotic properties, such as cholesterol reduction, and acid tolerance. 9,10 Animals also harbor beneficial bacteria, and several species, eg pigs, rats, and poultry, insects, eg honeybees, and fish are potential probiotic strain sources. 10 The Potential Roles of Probiotics and Prebiotics ...
... The major difference between vaginally delivered and exclusively breastfed infants, and those who are not, is their access to natural prebiotics (eg human milk oligosaccharides) and probiotics (eg maternal and breast milk microbes). 9,11 The human milk oligosaccharides (HMOs) found in breast milk are not digested by the infant, but rather they favor the growth of certain Bifidobacterium species and strains, eg B. longum subsp. infantis and B. bifidum. ...
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Background Gut microbiota play a key role in host health, with certain Bifidobacterium strains critical for immune development. The healthy gut of breastfed infants is dominated by these pioneer microbes, especially the strains that feed on human milk oligosaccharides. Objective This is a scoping review of gut microbiome research from Zimbabwe. It focuses on distribution and dynamic changes of bifidobacteria, and milk components that promote growth of microbes in infants, together with the distribution of associated gut microbes in adults. Design Online databases were searched for publications from 2000 to 2023. Results and Analysis Fourteen publications on microbiota of infants and adults were included in this scoping review. Most were cross-sectional, while three were clinical trials/cohort protocols. Publications focused on pediatrics (78.5%), pregnant women (14.3%), and men (7.2%). Zimbabwe has a high burden of HIV; hence 35.7% of study populations were delineated by HIV status. The laboratory methods used included shotgun metagenomics (62%) or 16S rRNA gene amplicon sequencing. Almost 85% of the studies focused on total microbiome profiles and rarely reported the distribution of different Bifidobacterium species and variants. None of the papers studied human breast milk composition. There were reports of reduced abundance of beneficial genera in pregnant women, children, and adolescents living with HIV. Additionally, gut microbiota was reported to be poorly predictive of child growth and vaccine response, though this was not conclusive. Conclusion There are few studies that characterize the gut microbiome by Zimbabwe-based researchers. However, studies on strain level diversity of Bifidobacterium and other key microbes, and their role in health during and beyond infancy, lag behind in Zimbabwe and other low- and middle-income countries. Such cohorts are needed to inform future mechanistic studies and downstream translational work such as next-generation probiotics and prebiotics.
... Bifidobacterium represents highly abundant and common members of the mammalian gut microbiota, especially during the host's infancy, while the relative abundance of Bifidobacterium may reduce to 15 % in the adult gut microbiota. Numerous studies have found a connection between decreased Bifidobacterium in the host gut microbiota and a number of metabolic, immunological and intestinal illness (Arboleya, Watkins, Stanton, & Ross, 2016;Derrien, Turroni, Ventura, & van Sinderen, 2022;O'Neill, Schofield, & Hall, 2017). The B-CPS and CS-Mix groups also possessed higher levels of Parabacteroides and Subdoligranulum compared to the NF group. ...
... Біфідобактерії -це грампозитивні, гетероферментативні, анаеробні бактерії з характерною біфідоподібною (тобто «Y») формою [1,2]. Рід Bifi dobacterium був вперше виділений із калу немовлят на грудному вигодовуванні у 1899 році Анрі Тіссьє [3]. Біфідобактерії колонізують кишечник новонароджених протягом перших днів і тижнів після народження і є найпоширенішим родом бактерій, що становить від 40 % до 80 % загальної мікробіоти кишечника [4,14]. ...
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The genus Bifi dobacterium has been shown to predominate in the gut microbiota of breastfed infants and to benefi t the body by accelerating maturation of the immune response, balancing the immune system to suppress infl ammation, improving intestinal barrier function, and increasing acetate production. The microfl ora of breastfed infants consists mainly of these bacteria, and their presence is considered important in early childhood because they maintain a healthy acid-alkaline balance necessary for the normal functioning of digestive enzymes, prevent the development of harmful bacteria, infl uence intestinal motility (peristalsis), and promote normal functioning of the immune system. Bifi dobacterium is well adapted to the infant gut and has evolved with the gut microbiome, in part due to its ability to consume the complex carbohydrates found in human milk.In order to provide the benefi ts associated with Bifi dobacterium to all infants, a number of commercial strains have been developed over the past decades. As new ingredients become available, their safety and suitability must be evaluated in preclinical and clinical studies. A review of the complete clinical data on the use of Bifi dobacterium in infant formula is essential to better understand its potential impact on infant health and development. In this article, we begin to summarize recent clinical trials using selected commercial strains of Bifi dobacterium.
... The correlation between Bifidobacterium species consumption and improved human health has been well documented [35]. Various illnesses [36,37] and aging [36][37][38] have been associated with reduced numbers of Bifidobacterium species, which, in a healthy population, positively impact the immune system [39] and are thus important for health August 24, 2023 Volume 14 Issue 4 Figure 5 The impact of ADS024 on microbiota diversity in the miniature swine fecal samples during the 28-d study. MiSeq compositional sequencing and bioinformatic analysis were performed to measure the impact of ADS024 on the microbiota in miniature swine fecal samples after 28 d using the: A: Shannon index for alpha diversity; B: Simpson diversity index for alpha diversity; C: UniFrac principal coordinates analysis (PCoA) for beta diversity. ...
... The correlation between Bifidobacterium species consumption and improved human health has been well documented [35]. Various illnesses [36,37] and aging [36][37][38] have been associated with reduced numbers of Bifidobacterium species, which, in a healthy population, positively impact the immune system [39] and are thus important for health August 24, 2023 Volume 14 Issue 4 Figure 5 The impact of ADS024 on microbiota diversity in the miniature swine fecal samples during the 28-d study. MiSeq compositional sequencing and bioinformatic analysis were performed to measure the impact of ADS024 on the microbiota in miniature swine fecal samples after 28 d using the: A: Shannon index for alpha diversity; B: Simpson diversity index for alpha diversity; C: UniFrac principal coordinates analysis (PCoA) for beta diversity. ...
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Background: The Centers for Disease Control and Prevention estimate that Clostridioides difficile (C. difficile) causes half a million infections (CDI) annually and is a major cause of total infectious disease death in the United States, causing inflammation of the colon and potentially deadly diarrhea. We recently reported the isolation of ADS024, a Bacillus velezensis (B. velezensis) strain, which demonstrated direct in vitro bactericidal activity against C. difficile, with minimal collateral impact on other members of the gut microbiota. In this study, we hypothesized that in vitro activities of ADS024 will translate in vivo to protect against CDI challenge in mouse models. Aim: To investigate the in vivo efficacy of B. velezensis ADS024 in protecting against CDI challenge in mouse models. Methods: To mimic disruption of the gut microbiota, the mice were exposed to vancomycin prior to dosing with ADS024. For the mouse single-dose study, the recovery of ADS024 was assessed via microbiological analysis of intestinal and fecal samples at 4 h, 8 h, and 24 h after a single oral dose of 5 × 108 colony-forming units (CFU)/mouse of freshly grown ADS024. The single-dose study in miniature swine included groups that had been pre-dosed with vancomycin and that had been exposed to a dose range of ADS024, and a group that was not pre-dosed with vancomycin and received a single dose of ADS024. The ADS024 colonies [assessed by quantitative polymerase chain reaction (qPCR) using ADS024-specific primers] were counted on agar plates. For the 28-d miniature swine study, qPCR was used to measure ADS024 levels from fecal samples after oral administration of ADS024 capsules containing 5 × 109 CFU for 28 consecutive days, followed by MiSeq compositional sequencing and bioinformatic analyses to measure the impact of ADS024 on microbiota. Two studies were performed to determine the efficacy of ADS024 in a mouse model of CDI: Study 1 to determine the effects of fresh ADS024 culture and ADS024 spore preparations on the clinical manifestations of CDI in mice, and Study 2 to compare the efficacy of single daily doses vs dosing 3 times per day with fresh ADS024. C. difficile challenge was performed 24 h after the start of ADS024 exposure. To model the human distal colon, an anerobic fecal fermentation system was used. MiSeq compositional sequencing and bioinformatic analyses were performed to measure microbiota diversity changes following ADS024 treatment. To assess the potential of ADS024 to be a source of antibiotic resistance, its susceptibility to 18 different antibiotics was tested. Results: In a mouse model of CDI challenge, single daily doses of ADS024 were as efficacious as multiple daily doses in protecting against subsequent challenge by C. difficile pathogen-induced disease. ADS024 showed no evidence of colonization based on the observation that the ADS024 colonies were not recovered 24 h after single doses in mice or 72 h after single doses in miniature swine. In a 28-d repeat-dose study in miniature swine, ADS024 was not detected in fecal samples using plating and qPCR methods. Phylogenetic analysis performed in the human distal colon model showed that ADS024 had a selective impact on the healthy human colonic microbiota, similarly to the in vivo studies performed in miniature swine. Safety assessments indicated that ADS024 was susceptible to all the antibiotics tested, while in silico testing revealed a low potential for off-target activity or virulence and antibiotic-resistance mechanisms. Conclusion: Our findings, demonstrating in vivo efficacy of ADS024 in protecting against CDI challenge in mouse models, support the use of ADS024 in preventing recurrent CDI following standard antibiotic treatment.
... Notably, Bifidobacterium and Megasphaera were also reported to be positively associated with the metformin treatment [17,20,22], highlighting the shared role of these taxa in the therapeutic effects of these drugs. Bifidobacterium is known for its beneficial health effects, including regulation of intestinal microbial homeostasis, modulation of local and systemic immune responses, inhibition of pathogens and harmful bacteria [47], improvement of the gut mucosal barrier, and lowering lipopolysaccharide levels in the intestine [48]. In addition, Bifidobacterium species can improve glucose homeostasis by enhancing expressions of insulin signalling proteins and improving the adipokine profile in diabetic mice [49]. ...
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Background: Although common drugs for treating type 2 diabetes (T2D) are widely used, their therapeutic effects vary greatly. The interaction between the gut microbiome and glucose-lowering drugs is one of the main contributors to the variability in T2D progression and response to therapy. On the one hand, glucose-lowering drugs can alter gut microbiome components. On the other hand, specific gut microbiota can influence glycemic control as the therapeutic effects of these drugs. Therefore, this systematic review assesses the bi-directional relationships between common glucose-lowering drugs and gut microbiome profiles. Methods: A systematic search of Embase, Web of Science, PubMed, and Google Scholar databases was performed. Observational studies and randomised controlled trials (RCTs), published from inception to July 2023, comprising T2D patients and investigating bi-directional interactions between glucose-lowering drugs and gut microbiome, were included. Results: Summarised findings indicated that glucose-lowering drugs could increase metabolic-healthy promoting taxa (e.g., Bifidobacterium) and decrease harmful taxa (e.g., Bacteroides and Intestinibacter). Our findings also showed a significantly different abundance of gut microbiome taxa (e.g., Enterococcus faecium (i.e., E. faecium)) in T2D patients with poor compared to optimal glycemic control. Conclusions: This review provides evidence for glucose-lowering drug and gut microbiome interactions, highlighting the potential of gut microbiome modulators as co-adjuvants for T2D treatment.
... They have become one of the main research interests due to their potential immunoregulatory [46,47] and anti-tumor activity on the host [22,48]. It was shown that Bifidobacterium can activate NK cells, T cells, and also macrophages to produce a wide spectrum of mediators playing a pivotal role in the control of inflammation [49][50][51]. It is assumed that there are two possible paths of immunomodulatory action of Bifidobacterium. ...
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Bifidobacterium species are one of the most important probiotic microorganisms which are present in both, infants and adults. Nowadays, growing data describing their healthy properties arise, indicating they could act at the cellular and molecular level. However, still little is known about the specific mechanisms promoting their beneficial effects. Nitric oxide (NO), produced by inducible nitric oxide synthase (iNOS), is involved in the protective mechanisms in the gastrointestinal tract, where it can be provided by epithelial cells, macrophages, or bacteria. The present study explored whether induction of iNOS-dependent NO synthesis in macrophages stems from the cellular action of Bifidobacterium species. The ability of ten Bifidobacterium strains belonging to 3 different species (Bifidobacterium longum, Bifidobacterium adolescentis, and Bifidobacterium animalis) to activate MAP kinases, NF-κB factor, and iNOS expression in a murine bone-marrow-derived macrophages cell line was determined by Western blotting. Changes in NO production were determined by the Griess reaction. It was performed that the Bifidobacterium strains were able to induce NF-қB-dependent iNOS expression and NO production; however, the efficacy depends on the strain. The highest stimulatory activity was observed for Bifidobacterium animalis subsp. animals CCDM 366, whereas the lowest was noted for strains Bifidobacterium adolescentis CCDM 371 and Bifidobacterium longum subsp. longum CCDM 372. Both TLR2 and TLR4 receptors are involved in Bifidobacterium-induced macrophage activation and NO production. We showed that the impact of Bifidobacterium on the regulation of iNOS expression is determined by MAPK kinase activity. Using pharmaceutical inhibitors of ERK 1/2 and JNK, we confirmed that Bifidobacterium strains can activate these kinases to control iNOS mRNA expression. Concluding, the induction of iNOS and NO production may be involved in the protective mechanism of action observed for Bifidobacterium in the intestine, and the efficacy is strain-dependent.
... Because the newborn gut is sterile, these useful microbes and their mechanisms must be attained during and after birth; this is accomplished through early colonization by pioneer bacteria, subsequent diversification, and variations in microbial population abundances over time until a stable microbiome is developed during early life (Sprockett et al., 2018). The gut microbiome's early colonization and development throughout childhood have an impact on physiological and immunological development (O'Neill et al., 2017). Due to the possibility that enteric microbes promote macromolecules and antigens past the gut epithelium, the gut microbiota has been linked to the immune response (Hou et al., 2022). ...
Article
The link between the gut microbiome and health has recently garnered considerable interest in its employment for medicinal purposes. Since the early microbiota exhibits more flexibility compared to that of adults, there is a considerable possibility that altering it will have significant consequences on human development. Like genetics, the human microbiota can be passed from mother to child. This provides information on early microbiota acquisition, future development, and prospective chances for intervention. The succession and acquisition of early-life microbiota, modifications of the maternal microbiota during pregnancy, delivery, and infancy, and new efforts to understand maternal-infant microbiota transmission are discussed in this article. We also examine the shaping of mother-to-infant microbial transmission, and we then explore possible paths for future research to advance our knowledge in this area.
... Due to their 'Generally Regarded as Safe' status, the commercial potential of certain Bifidobacterium spp. has driven much of the investigation into their purported benefits, which include positive effects on diarrhoeal disease 7,8 , resistance to microbial infection 9, 10 , risk of colorectal cancer 11,12 , and the immune system 13,14 . ...
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Background The composition of the infant microbiome can have a variety of short- and long-term implications for health. It is unclear if maternal probiotic supplementation in pregnancy can impact infant gut microbiome. Objective The aim of our study was to investigate if maternal supplementation of a formulation of Bifidobacterium breve 702258 from early pregnancy until three months postpartum could transfer to the infant gut. Study design This was a double-blinded placebo controlled randomised-controlled trial of B. breve 702258 (minimum 1x109 colony forming units) or placebo taken orally from 16-weeks gestation until three-months postpartum in healthy pregnant women. The primary outcome was presence of the supplemented strain in infant stool up to 3 months of life, detected by at a least two of three methods, i.e., strain specific PCR, shotgun metagenomic sequencing, or genome sequencing of cultured B. breve. 120 individual infant stool samples were required for 80% power to detect a difference in strain transfer between groups. Rates of detection were compared using Fishers exact test. Results 160 pregnant women with average age 33.6 (3.9) years, mean BMI of 24.3 (22.5, 26.5) kg/m2 and 43% with nulliparity (n=58) were recruited from September 2016 to July 2019. Neonatal stool samples were obtained from 135 infants (65 in intervention and 70 in control). The presence of the supplemented strain was detected through at least two methods (PCR and culture) in two infants in the intervention group (n=2/65, 3.1%) and none in the control group (n=0, 0%), p = 0.230. Conclusion Direct strain transfer from mothers to infants of B. breve 772058 occurred, albeit infrequently. This study highlights potential for maternal supplementation to introduce microbial strains into the infant microbiome.