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Potential mechanisms how Bifidobacterium lactis HN019™ (HN019) may modulate colonic motility in humans. The human intestinal epithelial cell layer comprises, among others, of epithelial cells (EC) and enterochromaffin cells (ECM) lining the gut wall. B. lactis HN019™ may stimulate Lactobacilli and Bifidobacteria and inhibit certain Gram-negative bacteria (G⁻ bacteria). Bacteria-derived and neurotransmitters or modulators of dietary origin, such as deconjugated bile acids (dBA), short chain fatty acids (SCFA), and serotonin (5-HT) could interact with their host receptors expressed in the epithelial cell layer; G protein-coupled receptors (GPR); and 5-HT receptors (5-HT R). Microvesicles (MV), peptidoglycan (PG), and lipopolysaccharide (LPS) from different bacteria interact with Toll-like receptors (TLRs). These components may also cross the epithelial layer and like the receptors signal afferent neurons in the enteric nervous system (ENS) with among others acetylcholine (ACh) to regulate colonic motility. Modified after Dalziel et al. (2021) (with permission). ©Pinja Kettunen/SciArt and IFF, with permission.
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Optimal gut motility is central to bowel function and gut health. The link between the gut dysmotility related disorders and dysfunctional-intestinal barriers has led to a hypothesis that certain probiotics could help in normalizing gut motility and maintain gut health. This review investigates the roles of Bifidobacterium animalis subsp. lactis HN...
Citations
... This probiotic species is positively associated with longevity in mice and negatively correlated with inflammation and obesity in humans. 45,46 Our data are in line with Zhang et al.'s report of a positive association between B. animalis spp. levels and survival of IAV-infected mice. ...
The gut-to-lung axis is critical during respiratory infections, including influenza A virus (IAV) infection. In the present study, we used high-resolution shotgun metagenomics and targeted metabolomic analysis to characterize influenza-associated changes in the composition and metabolism of the mouse gut microbiota. We observed several taxonomic-level changes on day (D)7 post-infection, including a marked reduction in the abundance of members of the Lactobacillaceae and Bifidobacteriaceae families, and an increase in the abundance of Akkermansia muciniphila. On D14, perturbation persisted in some species. Functional scale analysis of metagenomic data revealed transient changes in several metabolic pathways, particularly those leading to the production of short-chain fatty acids (SCFAs), polyamines, and tryptophan metabolites. Quantitative targeted metabolomics analysis of the serum revealed changes in specific classes of gut microbiota metabolites, including SCFAs, trimethylamine, polyamines, and indole-containing tryptophan metabolites. A marked decrease in indole-3-propionic acid (IPA) blood level was observed on D7. Changes in microbiota-associated metabolites correlated with changes in taxon abundance and disease marker levels. In particular, IPA was positively correlated with some Lactobacillaceae and Bifidobacteriaceae species (Limosilactobacillus reuteri, Lactobacillus animalis) and negatively correlated with Bacteroidales bacterium M7, viral load, and inflammation markers. IPA supplementation in diseased animals reduced viral load and lowered local (lung) and systemic inflammation. Treatment of mice with antibiotics targeting IPA-producing bacteria before infection enhanced viral load and lung inflammation, an effect inhibited by IPA supplementation. The results of this integrated metagenomic-metabolomic analysis highlighted IPA as an important contributor to influenza outcomes and a potential biomarker of disease severity.
... Previous studies on a similar strain, Bifidobacterium animalis subsp. lactis HN019, have demonstrated its ability to reduce intestinal transit time and increase bowel movement frequency in FC, possibly through SCFAs derived from microbial fermentation [38]. Therefore, the upregulated SCFAs metabolism could contribute to the amelioration of FC by regulating intestinal function. ...
Functional constipation (FC) can seriously affect the physical and mental health of children. The goal of this study is to assess the efficacy and safety of Bifidobacterium animalis subsp. lactis XLTG11 in treating FC in children through a randomized, double-blinded, placebo-controlled approach. Eligible children were randomized into either the intervention group (IG, n = 65, receiving conventional treatment with probiotics) or the control group (CG, n = 66, receiving conventional treatment without probiotics). The primary outcome measure was fecal frequency. Fecal gut microbiota analysis and PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) were used to predict gene family abundances based on 16S information. Over the course of treatment, the weekly frequency of feces within each group increased significantly ( F = 41.97, p < 0.001). The frequency of feces (times/week (t/w)) in the IG was significantly higher than that in the CG (3.69 ± 2.62 t/w vs.3.18 ± 1.43 t/w, 4.03 ± 2.54 t/w vs. 2.89 ± 1.39 t/w and 3.74 ± 2.36 t/w vs. 2.94 ± 1.18 t/w and 3.45 ± 1.98 vs. 3.17 ± 1.41 t/w for the 1st, 2nd, 3rd, and 4th week after intervention, respectively) ( F = 7.60, p = 0.0067). After the intervention, dominate species shifted to Bifidobacterium longum , Bifidobacterium breve , and Escherichia coli in the IG. Additionally, genes related to short-chain fatty acid (SCF) metabolism were upregulated, while methane metabolism was downregulated. Administration of XLTG11 at a dose of 1 × 10 ¹⁰ CFU/day to children increased fecal frequency, induced beneficial changes in gut microbiota, and regulated SCFs and methane metabolism–related genes.
... Numerous studies have demonstrated improved transit in patients with constipation. Administration of Bifidobacterium lactis HN019 and Bifidobacterium lactis DN-173 010 decreased transit time in adult subjects with chronic constipation [85]. Both in vitro and in human studies, B. lactis HN019™ reduced intestinal transit time in functional constipation by modulating the gut-brain-microbiota axis, mainly by the serotonin signalling pathway, via short-chain fatty acids produced by bacterial fermentation. ...
... Both in vitro and in human studies, B. lactis HN019™ reduced intestinal transit time in functional constipation by modulating the gut-brain-microbiota axis, mainly by the serotonin signalling pathway, via short-chain fatty acids produced by bacterial fermentation. B. lactis HN019™ is thus a probiotic that can improve the intestinal dysmotility-related disorders [85,86]. ...
Irritable bowel syndrome (IBS) is a common digestive disorder with a significant impact on both individuals and society in terms of quality of life and healthcare costs. A growing body of research has identified various communication pathways between the microbiota and the brain in relation to motility disorders, with the gut–brain axis being key to the pathogenesis of IBS. Multiple factors contribute to the pathogenetic pathways in IBS, including immune mechanisms, psychosocial factors, increased oxidative stress and pro-inflammatory cytokine release, as well as genetic and hormonal factors. Increased permeability of the normal intestinal barrier allows bacterial products to access the lamina propria, providing a mechanism for perpetuating chronic inflammation and characteristic symptoms. The microbiota influences inflammatory processes in IBS by altering the balance between pro-inflammatory factors and host defence. Probiotics modulate the pathophysiological mechanisms involved in IBS by influencing the composition of the microbiota and improving intestinal motility disorders, visceral hypersensitivity, immune function of the intestinal epithelium, metabolic processes in the intestinal lumen, dysfunction of the microbiota-GBA, and are recognised as effective and safe in IBS therapy. Our study aimed to provide a comprehensive overview of the relationship between the gut–brain axis, microbiota, and IBS, based on current information.
... B. lactis strains are widely used in a variety of dairy products or fermented foods [57,58], and their use as probiotics has been extensively documented in newborns, children, and adults [26,[59][60][61][62][63]. The B. lactis subspecies was described as a strict monophyletic bifidobacterial taxon [64]. ...
The influence of microbiota dysbiosis in early life is increasingly recognized as a risk factor for the development of several chronic diseases later in life, including an increased risk of asthma, eczema, allergies, obesity, and neurodevelopmental disorders. The question whether the potential lifelong consequences of early life dysbiosis could be mitigated by restoring microbiota composition remains unresolved. However, the current evidence base suggests that protecting the normal development of the microbiome during this critical developmental window could represent a valuable public health strategy to curb the incidence of chronic and lifestyle-related diseases. Probiotic Bifidobacteria are likely candidates for this purpose in newborns and infants considering the natural dominance of this genus on microbiota composition in early life. Moreover, the most frequently reported microbiota composition alteration in association with newborn and infant diseases, including necrotizing enterocolitis and diarrhea, is a reduction in Bifidobacteria levels. Several studies have assessed the effects of B. animalis subsp. lactis strains in newborns and infants, but recent expert opinions recommend analyzing their efficacy at the strain-specific level. Hence, using the B94 strain as an example, this review summarizes the clinical evidence available in infants and children in various indications, discussing the safety and potential modes of actions while providing perspectives on the concept of “non-infant-type” probiotics for infants’ health.
... polymorphonuclear cell phagocytosis, and NK cell killing activity. 16,24 Likewise, L. rhamnosus HN001 has also been suggested to enhance natural and acquired immunity in animal and human experiments. 14,25 Additionally, we also observed an increase in the concentration of fecal sIgA, which was widely used as a marker of mucosal immunity. ...
Synbiotics are increasingly used by the general population to boost immunity. However, there is limited evidence concerning the immunomodulatory effects of synbiotics in healthy individuals. Therefore, we conducted a double-blind, randomized, placebo-controlled study in 106 healthy adults. Participants were randomly assigned to receive either synbiotics (containing Bifidobacterium lactis HN019 1.5 × 10⁸ CFU/d, Lactobacillus rhamnosus HN001 7.5 × 10⁷ CFU/d, and fructooligosaccharide 500 mg/d) or placebo for 8 weeks. Immune parameters and gut microbiota composition were measured at baseline, mid, and end of the study. Compared to the placebo group, participants receiving synbiotic supplementation exhibited greater reductions in plasma C-reactive protein (P = 0.088) and interferon-gamma (P = 0.008), along with larger increases in plasma interleukin (IL)-10 (P = 0.008) and stool secretory IgA (sIgA) (P = 0.014). Additionally, synbiotic supplementation led to an enrichment of beneficial bacteria (Clostridium_sensu_stricto_1, Lactobacillus, Bifidobacterium, and Collinsella) and several functional pathways related to amino acids and short-chain fatty acids biosynthesis, whereas reduced potential pro-inflammatory Parabacteroides compared to baseline. Importantly, alternations in anti-inflammatory markers (IL-10 and sIgA) were significantly correlated with microbial variations triggered by synbiotic supplementation. Stratification of participants into two enterotypes based on pre-treatment Prevotella-to-Bacteroides (P/B) ratio revealed a more favorable effect of synbiotic supplements in individuals with a higher P/B ratio. In conclusion, this study suggested the beneficial effects of synbiotic supplementation on immune parameters, which were correlated with synbiotics-induced microbial changes and modified by microbial enterotypes. These findings provided direct evidence supporting the personalized supplementation of synbiotics for immunomodulation.
... lactis HN019 (HN019) has a long history of use as a probiotic, and its health benefits have been demonstrated in numerous human clinical trials. These trials have investigated HN019 s ability to modulate the immune system [1], improve colonic transit time and constipation [2] and reduce childhood morbidity in the developing world [3] when given with a prebiotic in fortified milk [4]. Probiotics, by definition, are 'live microorganisms that, when administered in adequate amounts, confer a health benefit on the host', with the health benefits being strain specific to the microorganism [5]. ...
Bifidobacterium animalis subsp. lactis HN019 is a probiotic with several documented human health benefits. Interest in probiotics has led to the development of new formats that probiotics, including HN019, can be supplemented into. In this study, we looked at common HN019 formats such as frozen culture and freeze-dried powder as well as supplementing it into the following food matrices: yogurts (dairy, soy, and oat based), xanthan gum-based tablets, pulpless orange juice, whey sports drink, and dark chocolate (70% cocoa). In this work, our aim was to investigate whether the food matrix that carried HN019 via simulated human digestion (a dual model system mimicking both upper and lower gastrointestinal digestion) influenced probiotic delivery. To that end, we validated and used a real-time qPCR assay to detect HN019 after simulated digestion. In addition, we also measured the effect on a panel of metabolites. After simulated digestion, we were able to detect HN019 from all the matrices tested, and the observed changes to the metabolite profile were consistent with those expected from the food matrix used. In conclusion, this work suggests that the food matrix supplemented with HN019 did not interfere with delivery to the colon via simulated human digestion.
... It is known that when macrophages are activated by interferons (IFN) or LPS, the phenotype M1 results. On the other hand, when the activation is performed by interleukins (IL-4 or IL-13), immune complexes, or glucocorticoids, the phenotype M2 is the result [43,44]. The M1 macrophages have an inflammatory role and are generally activated by intracellular pathogens, LPS, IFN-γ and TNF-α among others. ...
Probiotics play an important role against infectious pathogens, such as Escherichia coli (E. coli), mainly through the production of antimicrobial compounds and their immunomodulatory effect. This protection can be detected both on the live probiotic microorganisms and in their inactive forms (paraprobiotics). Probiotics may affect different cells involved in immunity, such as macrophages. Macrophages are activated through contact with microorganisms or their products (lipopolysaccharides, endotoxins or cell walls). The aim of this work was the evaluation of the effect of two probiotic bacteria (Escherichia coli Nissle 1917 and Bifidobacterium animalis subsp. lactis HN019 on macrophage cell line J774A.1 when challenged with two pathogenic strains of E. coli. Macrophage activation was revealed through the detection of reactive oxygen (ROS) and nitrogen (RNS) species by flow cytometry. The effect varied depending on the kind of probiotic preparation (immunobiotic, paraprobiotic or postbiotic) and on the strain of E. coli (enterohemorrhagic or enteropathogenic). A clear immunomodulatory effect was observed in all cases. A higher production of ROS compared with RNS was also observed.
... In contrast, participants in the S2 + BB12 group (n = 28) were administered the base yogurt beverage that was supplemented with an additional 1 × 10 10 colony-forming units of BB12 per serving per day. BB12 was chosen as the interventional probiotic of interest as it has been widely studied in infants and children (Merenstein et al., 2010(Merenstein et al., , 2011Goldenberg et al., 2015;Merenstein et al., 2021), and is associated with positive gastrointestinal protective mechanisms including maintenance of tight junction function and immune regulation in the gut (Uusitupa et al., 2020;Cheng et al., 2021). The yogurt was administered to the participants in both groups for ten consecutive days. ...
Introduction
The consumption of probiotics may influence children’s gut microbiome and metabolome, which may reflect shifts in gut microbial diversity composition and metabolism. These potential changes might have a beneficial impact on health. However, there is a lack of evidence investigating the effect of probiotics on the gut microbiome and metabolome of children. We aimed to examine the potential impact of a two ( Streptococcus thermophilus and Lactobacillus delbrueckii ; S2) vs. three (S2 + Bifidobacterium animalis subsp . lactis strain BB-12) strain-supplemented yogurt.
Methods
Included in this study were 59 participants, aged one to five years old, recruited to phase I of a double-blinded, randomized controlled trial. Fecal samples were collected at baseline, after the intervention, and at twenty days post-intervention discontinuation, and untargeted metabolomics and shotgun metagenomics were performed.
Results
Shotgun metagenomics and metabolomic analyses showed no global changes in either intervention group’s gut microbiome alpha or beta diversity indices, except for a lower microbial diversity in the S2 + BB12 group at Day 30. The relative abundance of the two and three intervention bacteria increased in the S2 and S2 + BB12 groups, respectively, from Day 0 to Day 10. In the S2 + BB12 group, the abundance of several fecal metabolites increased at Day 10, including alanine, glycine, lysine, phenylalanine, serine, and valine. These fecal metabolite changes did not occur in the S2 group.
Discussion
In conclusion, there were were no significant differences in the global metagenomic or metabolomic profiles between healthy children receiving two (S2) vs. three (S2 + BB12) probiotic strains for 10 days. Nevertheless, we observed a significant increase (Day 0 to Day 10) in the relative abundance of the two and three probiotics administered in the S2 and S2 + BB12 groups, respectively, indicating the intervention had a measurable impact on the bacteria of interest in the gut microbiome. Future research using longer probiotic intervention durations and in children at risk for gastrointestinal disorders may elucidate if functional metabolite changes confer a protective gastrointestinal effect.
... In fact, the use of B. lactis HN019 as a promising therapeutic strategy in PE and MS has been well documented in several clinical 14,[34][35][36] and preclinical studies 26,27,[37][38][39] . This probiotic strain can modify the microbiology of the intestinal environment and the expression of adipokines in white adipose tissue 40,41 . It is currently known that the intestine and adipose tissue may play a relevant role in the etiopathogenesis of the association MS-PE [42][43][44] . ...
Background:
This study evaluated the systemic (intestine and adipose tissue) and local (periodontal tissues) impact of probiotic therapy in rats with metabolic syndrome (MS) associated or not with periodontitis (PE).
Methods:
Forty-eight rats received a high-fat diet for induction of MS for 16 weeks. They were subdivided into groups with (+) and without (-) PE, receiving (*) or not (**) probiotic (PROB): MS-, MSP-*, MSPE+**, and MSPEP+*. PROB administration (Bifidobacterium animalis subsp. lactis HN019) started on the eighth week of the study and PE was induced on the 14th week by placing ligature on the animals' lower first molars. Euthanasia occurred in the 16th week. Biomolecular, immunoenzymatic assays, and histomorphometric analyses were performed. The data obtained were statistically analyzed (ANOVA, Tukey, p<0.05).
Results:
The MSPEP group exhibited reduced alveolar bone loss when compared with the MSPE group, as well as lower levels of hepatic steatosis and proteinuria (p<0.05). In the intestinal environment, the MSPE group exhibited significantly lower villus height and crypt depth, as well as a greater increase in Bacillota when compared with the MSPEP group (p<0.05). The MSPEP group showed lower adipokine gene expression (FABP4, NAMPT and LEPR) in adipose tissue than the MSPE group (p<0.05).
Conclusion:
The probiotic B. lactis HN019 reduced the severity of experimental periodontitis and modulated the expression of lipogenic genes and intestinal morphological and microbiological parameters in rats with MS. This article is protected by copyright. All rights reserved.
... Prospective studies are needed to analyze alterations in metabolite production from gut microbial modulation production and the indirect impacts of their vitamins on immunotherapy response. There are many immune-related adverse events (AEs) that occur in ICI treatments, such as colitis and peripheral neuropathy [274][275][276][277][278]. Several bacterial species, including Bacteroidaceae, Bifidobacterium animalis, Bifidobacteria infantis, Faecalibacterium prausnitzii, and Lactobacillaceae are associated with the maintenance of tolerogenic responses in the gut [51,264,[279][280][281][282][283][284][285][286][287][288][289]. The bacteria are deemed protective against ICI-induced colitis through nitric oxide production, shifts in the Th1/Th2 balance, and induced Treg differentiation. ...
Simple Summary
Despite clinical success, only a limited percentage of cancer patients are responsive to immunotherapy. Recently, gut microbiota modulation has been suggested as a tool to enhance immunotherapy efficacy, and mechanisms for these effects may be linked to microbial contributions—such as microbial-derived vitamins—to immune responses. While humans can acquire their vitamins from dietary sources, gut microbial-derived vitamins are crucial to the immune system’s function. The production of these vitamins can be altered by the bidirectional crosstalk between the immune system and the gut microbiome; however, their exact mechanism of action in bacterial communities and immune responses remains elusive. Further studies and clinical trials are needed to understand the role of microbial-derived vitamins in anti-tumor immune responses and their role in the efficacy of immunotherapies. This review will discuss the in-depth mechanisms of selective vitamins and their role in modulating immune responses, as well as their potential as immunotherapy enhancers.
Abstract
Not all cancer patients who receive immunotherapy respond positively and emerging evidence suggests that the gut microbiota may be linked to treatment efficacy. Though mechanisms of microbial contributions to the immune response have been postulated, one likely function is the supply of basic co-factors to the host including selected vitamins. Bacteria, fungi, and plants can produce their own vitamins, whereas humans primarily obtain vitamins from exogenous sources, yet despite the significance of microbial-derived vitamins as crucial immune system modulators, the microbiota is an overlooked source of these nutrients in humans. Microbial-derived vitamins are often shared by gut bacteria, stabilizing bioenergetic pathways amongst microbial communities. Compositional changes in gut microbiota can affect metabolic pathways that alter immune function. Similarly, the immune system plays a pivotal role in maintaining the gut microbiota, which parenthetically affects vitamin biosynthesis. Here we elucidate the immune-interactive mechanisms underlying the effects of these microbially derived vitamins and how they can potentially enhance the activity of immunotherapies in cancer.
