Restorative effects of probiotics on memory impairment in sleep-deprived mice.

BACKGROUND: Insufficient sleep is a serious public health epidemic in modern society, impairing memory and other cognitive functions. In this study, partial sleep deprivation (SD) was used to induce cognitive impairment in mice to determine the effects of probiotics on subsequent cognitive deficits. METHODS: Lactiplantibacillus plantarum Lp-115 (Lp-115), Lacticaseibacillus paracasei Lpc-37 (Lpc-37), Bifidobacterium animalis subsp. lactis 420 (B420) and their combination were administered to mice subjected to partial SD and compared with non-SD and SD vehicle groups. Mice were administered a daily oral gavage containing either 1 × 109 colony forming units (CFU) of single-strain, 1.5 × 109 CFU of multi-strain (5 × 108 CFU/strain), or vehicle for thirty days prior to and for nine days during a behavioural test paradigm. The novel object recognition (NOR) test, spontaneous alternation Y-maze (Y-maze), and the step-through passive avoidance (STPA) task were applied to evaluate learning and memory performance following partial SD. RESULTS: Partial SD had a significant impact on cognitive function in vehicle mice. Intervention with Lpc-37 significantly improved recognition memory deficits in the NOR test, spatial working memory deficits in the Y-maze, and contextual long-term memory impairments in the STPA task, in mice subjected to partial SD compared to the SD vehicle group. The multi-strain significantly improved recognition memory deficits in the NOR test and spatial working memory deficits in the Y-maze in mice subjected to partial SD compared to the SD vehicle group. CONCLUSIONS: These findings demonstrate that Lpc-37 and the multi-strain may play a role in alleviating memory impairments and improve cognitive function in partially sleep-deprived mice.

Single-Cell Tracking Reveals a Role for Pre-Existing CCR5+ Memory Th1 Cells in the Control of Rhinovirus-A39 After Experimental Challenge in Humans.

Background: Little is known about T cells that respond to human rhinovirus in vivo, due to timing of infection, viral diversity, and complex T-cell specificities. We tracked circulating CD4+ T cells with identical epitope specificities that responded to intranasal challenge with rhinovirus (RV)-A39, and we assessed T-cell signatures in the nose. Methods: Cells were monitored using a mixture of 2 capsid-specific major histocompatibility complex II tetramers over a 7-week period, before and after RV-A39 challenge, in 16 human leukocyte antigen-DR4+ subjects who participated in a trial of Bifidobacterium lactis (Bl-04) supplementation. Results: Pre-existing tetramer+ T cells were linked to delayed viral shedding, enriched for activated CCR5+ Th1 effectors, and included a minor interleukin-21+ T follicular helper cell subset. After RV challenge, expansion and activation of virus-specific CCR5+ Th1 effectors was restricted to subjects who had a rise in neutralizing antibodies, and tetramer-negative CCR5+ effector memory types were comodulated. In the nose, CXCR3-CCR5+ T cells present during acute infection were activated effector memory type, whereas CXCR3+ cells were central memory type, and cognate chemokine ligands were elevated over baseline. Probiotic had no T-cell effects. Conclusions: We conclude that virus-specific CCR5+ effector memory CD4+ T cells primed by previous exposure to related viruses contribute to the control of rhinovirus.

Mutations in Complement Factor H Impair Alternative Pathway Regulation on Mouse Glomerular Endothelial Cells in Vitro.

Complement factor H (FH) inhibits complement activation and interacts with glomerular endothelium via its complement control protein domains 19 and 20, which also recognize heparan sulfate (HS). Abnormalities in FH are associated with the renal diseases atypical hemolytic uremic syndrome and dense deposit disease and the ocular disease age-related macular degeneration. Although FH systemically controls complement activation, clinical phenotypes selectively manifest in kidneys and eyes, suggesting the presence of tissue-specific determinants of disease development. Recent results imply the importance of tissue-specifically expressed, sulfated glycosaminoglycans (GAGs), like HS, in determining FH binding to and activity on host tissues. Therefore, we investigated which GAGs mediate human FH and recombinant human FH complement control proteins domains 19 and 20 (FH19-20) binding to mouse glomerular endothelial cells (mGEnCs) in ELISA. Furthermore, we evaluated the functional defects of FH19-20 mutants during complement activation by measuring C3b deposition on mGEnCs using flow cytometry. FH and FH19-20 bound dose-dependently to mGEnCs and TNF-α treatment increased binding of both proteins, whereas heparinase digestion and competition with heparin/HS inhibited binding. Furthermore, 2-O-, and 6-O-, but not N-desulfation of heparin, significantly increased the inhibitory effect on FH19-20 binding to mGEnCs. Compared with wild type FH19-20, atypical hemolytic uremic syndrome-associated mutants were less able to compete with FH in normal human serum during complement activation on mGEnCs, confirming their potential glomerular pathogenicity. In conclusion, our study shows that FH and FH19-20 binding to glomerular endothelial cells is differentially mediated by HS but not other GAGs. Furthermore, we describe a novel, patient serum-independent competition assay for pathogenicity screening of FH19-20 mutants.

The effect of an apple polyphenol extract rich in epicatechin and flavan-3-ol oligomers on brachial artery flow-mediated vasodilatory function in volunteers with elevated blood pressure.

BACKGROUND: The primary aim of this study was to test the hypothesis that an orally ingested apple polyphenol extract rich in epicatechin and flavan-3-ol oligomers improves endothelium-dependent brachial artery flow-mediated vasodilatation (FMD) in volunteers with borderline hypertension. The secondary aim of the study was to test whether the investigational product would improve endothelium-independent nitrate-mediated vasodilatation (NMD). METHODS: This was a single centre, repeated-dose, double-blind, placebo-controlled, crossover study in 60 otherwise healthy subjects (26 men, 34 women; aged 40-65 years) with borderline hypertension (blood pressure 130-139/85-89 mmHg) or unmedicated mild hypertension (blood pressure 140-165/90-95 mmHg). The subjects were randomised to receive placebo or the apple polyphenol extract to provide a daily dose of 100 mg epicatechin for 4 weeks, followed by a four to five-week wash-out period, and then 4 weeks intake of the product that they did not receive during the first treatment period. FMD and NMD of the left brachial artery were investigated with ultrasonography at the start and end of both treatment periods, and the per cent increase of the arterial diameter (FMD% and NMD%) was calculated. RESULTS: With the apple extract treatment, a significant acute improvement was detected in the mean change of maximum FMD% at the first visit 1.16 (p = 0.04, 95% CI: 0.04; 2.28), last visit 1.37 (p = 0.02, 95% CI: 0.22; 2.52) and for both visits combined 1.29 (p < 0.01, 95% CI: 0.40; 2.18). However, such improvement was not statistically significant when apple extract was compared with placebo. The overall long-term effect of apple extract on FMD% was not different from placebo. No statistically significant differences between the apple extract and placebo treatments were observed for endothelium-independent NMD. CONCLUSIONS: A significant acute improvement in maximum FMD% with apple extract administration was found. However, superiority of apple extract over placebo was not statistically significant in our study subjects with borderline hypertension or mild hypertension. The study raised no safety concerns regarding the daily administration of an apple polyphenol extract rich in epicatechin. TRIAL REGISTRATION: The trial is registered at http://clinicaltrials.gov (identifier: NCT01690676 ). Registered 25th May 2012.

Structural basis for complement evasion by Lyme disease pathogen Borrelia burgdorferi.

Borrelia burgdorferi spirochetes that cause Lyme borreliosis survive for a long time in human serum because they successfully evade the complement system, an important arm of innate immunity. The outer surface protein E (OspE) of B. burgdorferi is needed for this because it recruits complement regulator factor H (FH) onto the bacterial surface to evade complement-mediated cell lysis. To understand this process at the molecular level, we used a structural approach. First, we solved the solution structure of OspE by NMR, revealing a fold that has not been seen before in proteins involved in complement regulation. Next, we solved the x-ray structure of the complex between OspE and the FH C-terminal domains 19 and 20 (FH19-20) at 2.83 Å resolution. The structure shows that OspE binds FH19-20 in a way similar to, but not identical with, that used by endothelial cells to bind FH via glycosaminoglycans. The observed interaction of OspE with FH19-20 allows the full function of FH in down-regulation of complement activation on the bacteria. This reveals the molecular basis for how B. burgdorferi evades innate immunity and suggests how OspE could be used as a potential vaccine antigen.

Dual interaction of factor H with C3d and glycosaminoglycans in host-nonhost discrimination by complement.

The alternative pathway of complement is important in innate immunity, attacking not only microbes but all unprotected biological surfaces through powerful amplification. It is unresolved how host and nonhost surfaces are distinguished at the molecular level, but key components are domains 19-20 of the complement regulator factor H (FH), which interact with host (i.e., nonactivator surface glycosaminoglycans or sialic acids) and the C3d part of C3b. Our structure of the FH19-20:C3d complex at 2.3-Å resolution shows that FH19-20 has two distinct binding sites, FH19 and FH20, for C3b. We show simultaneous binding of FH19 to C3b and FH20 to nonactivator surface glycosaminoglycans, and we show that both of these interactions are necessary for full binding of FH to C3b on nonactivator surfaces (i.e., for target discrimination). We also show that C3d could replace glycosaminoglycan binding to FH20, thus providing a feedback control for preventing excess C3b deposition and complement amplification. This explains the molecular basis of atypical hemolytic uremic syndrome, where mutations on the binding interfaces between FH19-20 and C3d or between FH20 and glycosaminoglycans lead to complement attack against host surfaces.

The effect of probiotic Bifidobacterium lactis Bl-04 on innate antiviral responses invitro.

Consumption of certain probiotic strains may be beneficial for reducing the risk of acute upper respiratory tract infections (URTIs), however, underlying immunological mechanisms are elusive. Bifidobacterium lactis Bl-04™ has been reported in humans to significantly reduce the risk of URTIs, affect the innate immunity in the nasal mucosa, and reduce nasal lavage virus titer after a rhinovirus (RV) challenge. To study the immunological mechanisms, we investigated the effect of Bl-04 on cytokine production and transcriptomes of human monocyte-derived macrophages (Mfs) and dendritic cells (DCs), and further on RV replication and cytokine production in MRC-5 fibroblasts. The results showed that Bl-04 modulates antiviral immune responses and potentiates cytokine production during viral challenge mimic in immune cells. However, effect of Bl-04 on RV replication and cytokine production in fibroblasts was negligible. Overall, the findings suggest that Bl-04 mildly stimulates antiviral immunity in Mfs and DCs, and potentially influences viral replication in fibroblasts that however warrants further investigations.

Enhancing Bioaccessibility of Plant Protein Using Probiotics: An In Vitro Study.

As plant-based diets become more popular, there is an interest in developing innovations to improve the bioaccessibility of plant protein. In this study, seven probiotic strains (Bifidobacterium animalis subsp. lactis B420, B. lactis Bl-04, Lactobacillus acidophilus NCFM, Lacticaseibacillus rhamnosus HN001, Lacticaseibacillus paracasei subsp. paracasei Lpc-37, Lactiplantibacillus plantarum Lp-115, and Lactococcus lactis subsp. lactis Ll-23) were evaluated for their capacity to hydrolyze soy and pea protein ingredients in an in vitro digestion model of the upper gastrointestinal tract (UGIT). Compared to the control digestion of protein without a probiotic, all the studied strains were able to increase the digestion of soy or pea protein, as evidenced by an increase in free α-amino nitrogen (FAN) and/or free amino acid concentration. The increase in FAN varied between 13 and 33% depending on the protein substrate and probiotic strain. The survival of probiotic bacteria after exposure to digestive fluids was strain-dependent and may have affected the strain's capacity to function and aid in protein digestion in the gastrointestinal environment. Overall, our results from the standardized in vitro digestion model provide an approach to explore probiotics for improved plant protein digestion and bioaccessibility of amino acids; however, human clinical research is needed to evaluate the efficacy of probiotics on amino acid absorption and bioavailability in vivo.

Lactobacillus acidophilus NCFM and Lactiplantibacillus plantarum Lp-115 inhibit Helicobacter pylori colonization and gastric inflammation in a murine model.

Purpose: To determine the role of Lactobacillus strains and their combinations in inhibiting the colonization of H. pylori and gastric mucosa inflammation. Methods: Human gastric adenocarcinoma AGS cells were incubated with H. pylori and six probiotic strains (Lactobacillus acidophilus NCFM, L. acidophilus La-14, Lactiplantibacillus plantarum Lp-115, Lacticaseibacillus paracasei Lpc-37, Lacticaseibacillus rhamnosus Lr-32, and L. rhamnosus GG) and the adhesion ability of H. pylori in different combinations was evaluated by fluorescence microscopy and urease activity assay. Male C57BL/6 mice were randomly divided into five groups (uninfected, H. pylori, H. pylori+NCFM, H. pylori+Lp-115, and H. pylori+NCFM+Lp-115) and treated with two lactobacilli strains (NCFM and Lp-115) for six weeks. H. pylori colonization and tissue inflammation statuses were determined by rapid urease test, Hematoxylin-Eosin (HE) staining, immunohistochemistry, and qRT-PCR and ELISA. Results: L. acidophilus NCFM, L. acidophilus La-14, L. plantarum Lp-115, L. paracasei Lpc-37, L. rhamnosus Lr-32, and L. rhamnosus GG reduced H. pylori adhesion and inflammation caused by H. pylori infection in AGS cells and mice. Among all probiotics L. acidophilus NCFM and L. plantarum, Lp-115 showed significant effects on the H. pylori eradication and reduction of inflammation in-vitro and in-vivo. Compared with the H. pylori infection group, the mRNA and protein expression levels of IL-8 and TNF-α in the six Lactobacillus intervention groups were significantly reduced. The changes in the urease activity (ureA and ureB) for 1-7h in each group showed that L. acidophilus NCFM, L. acidophilus La-14, L. plantarum Lp-115, and L. rhamnosus GG effectively reduced the colonization of H. pylori. We observed a higher ratio of lymphocyte and plasma cell infiltration into the lamina propria of the gastric mucosa and neutrophil infiltration in H. pylori+NCFM+Lp-115 mice. The infiltration of inflammatory cells in lamina propria of the gastric mucosa was reduced in the H. pylori+NCFM+Lp-115 group. Additionally, the expression of IFN-γ was decreased significantly in the NCFM and Lp-115 treated C57BL/6 mice. Conclusions: L. acidophilus NCFM and L. plantarum Lp-115 can reduce the adhesion of H. pylori and inhibit the gastric inflammatory response caused by H. pylori infection.

The Effect of Bifidobacterium animalis subsp. lactis Bl-04 on Influenza A Virus Infection in Mice.

Influenza A virus infection is a major global disease requiring annual vaccination. Clinical studies indicate that certain probiotics may support immune function against influenza and other respiratory viruses, but direct molecular evidence is scarce. Here, mice were treated with a placebo or Bifidobacterium animalis subsp. lactis Bl-04 (Bl-04) orally via food (cereal) and also by gavage and exposed to Influenza A virus H1N1 (H1N1). The symptoms of the infection were observed, and tissues and digesta were collected for viral load RT-qPCR, transcriptomics, and microbiomics. The treatment decreased the viral load by 48% at day 3 post-infection in lungs and symptoms of infection at day 4 compared to placebo. Tissue transcriptomics showed differences between the Bl-04 and placebo groups in the genes in the Influenza A pathway in the intestine, blood, and lungs prior to and post-infection, but the results were inconclusive. Moreover, 16S rRNA gene profiling and qPCR showed the presence of Bl-04 in the intestine, but without major shifts in the microbiome. In conclusion, Bl-04 treatment may influence the host response against H1N1 in a murine challenge model; however, further studies are required to elucidate the mechanism of action.

A Healthy Vaginal Microbiota Remains Stable during Oral Probiotic Supplementation: A Randomised Controlled Trial.

The primary objective of this randomised, placebo-controlled, triple-blind study was to assess whether orally consumed Lactobacillus acidophilus La-14 (La-14) and Lacticaseibacillus rhamnosus HN001 (HN001) colonise a healthy human vagina. Furthermore, potential effects on vaginal microbiota and immune markers were explored. Fifty women devoid of vaginal complaints (Nugent score 0-3 and vaginal pH ≤ 4.5) were randomised into a 2-week intervention with either La-14 and HN001 as the verum product or a comparable placebo. Vaginal swab samples were collected at baseline, after one and two weeks of intervention, and after a one-week follow-up, for assessing colonisation of the supplemented lactobacilli, vaginal microbiota, and six specific immune markers. Colonisation of L. acidophilus and L. rhamnosus was not observed above the assay detection limit (5.29 and 5.11 log 10 genomes/swab for L. acidophilus and L. rhamnosus, respectively). Vaginal microbiotas remained stable and predominated by lactobacilli throughout the intervention, and vaginal pH remained optimal (at least 90% of participants in both groups had pH 4.0 or 4.5 throughout the study). Immune markers elafin and human ß-defensin 3 (HBD-3) were significantly decreased in the verum group (p = 0.022 and p = 0.028, respectively) but did not correlate with any microbiota changes. Adverse events raised no safety concerns, and no undesired changes in the vaginal microbiota or immune markers were detected.

The effect of the probiotic consortia on SARS-CoV-2 infection in ferrets and on human immune cell response in vitro.

Probiotics have been suggested as one solution to counter detrimental health effects by SARS-CoV-2; however, data so far is scarce. We tested the effect of two probiotic consortia, OL-1 and OL-2, against SARS-CoV-2 in ferrets and assessed their effect on cytokine production and transcriptome in a human monocyte-derived macrophage (Mf) and dendritic cell (DC) model. The results showed that the consortia significantly reduced the viral load, modulated immune response, and regulated viral receptor expression in ferrets compared to placebo. In the human Mf and DC model, OL-1 and OL-2-induced cytokine production and genes related to SARS-CoV-2 antiviral immunity. The study results indicate that probiotic stimulation of the ferret immune system leads to improved antiviral immunity against SARS-COV-2, and the genes and cytokines associated with anti-SARS-CoV-2 immunity are stimulated in human immune cells in vitro. The effect of the consortia against SARS-CoV-2 warrants further investigations in human clinical trials.

Effect of Bifidobacterium animalis spp. lactis Bl-04 on Rhinovirus-Induced Colds: A Randomized, Placebo-Controlled, Single-Center, Phase II Trial in Healthy Volunteers.

BACKGROUND: This study was designed to assess the efficacy of Bifidobacterium animalis ssp. lactis (Bl-04) for prevention of rhinovirus colds and to explore the interactions between the probiotic, the viral infection, the host response and the host microbiome. METHODS: The effect of ingestion of the probiotic Bl-04 was evaluated in a randomized, double-blinded rhinovirus (RV) challenge study. Healthy volunteers recruited from a university community in USA were randomized 1:1 using a computer generated code to ingest either Bl-04 (n=165) or placebo (n=169) for 28 days and were then challenged with RV-A39, and followed for 14 days. All study interactions and sample collection occurred in dedicated clinical research space. The primary analysis was the effect of the probiotic on the incidence of RV-associated illness. (Trial registration: NCT02679807, study complete). FINDINGS: The first cohort of volunteers was randomized on March 14, 2016 and the last (5th) cohort was randomized on March 12, 2018. Sixty-three (56%, 95% CI [47%; 66%]) of the 112 subjects in the active group and 60 (50%,95% CI [41%; 59%]) of the 120 subjects in the placebo group had a protocol-defined rhinovirus-associated illness (χ2=0·91, p=0·34). The point estimate of the difference in illness (active-placebo) is 6.3% (95% CI -6.7;19.1). There were no adverse events that were judged as definitely or probably related to the study product. INTERPRETATION: In this study there was no effect of orally administered Bl-04 on the occurrence of RV-associated illness. FUNDING: Danisco Sweeteners Oy (now IFF Health & Biosciences).

Binding of the long pentraxin PTX3 to factor H: interacting domains and function in the regulation of complement activation.

The long pentraxin PTX3 is a multifunctional soluble molecule involved in inflammation and innate immunity. As an acute phase protein, PTX3 binds to the classical pathway complement protein C1q, limits tissue damage in inflammatory conditions by regulating apoptotic cell clearance, and plays a role in the phagocytosis of selected pathogens. This study was designed to investigate the interaction of PTX3 with factor H (FH), the main soluble alternative pathway regulatory protein. We report that PTX3 binds FH with an apparent K(d) of 1.1 x 10(-7) M, and define two binding sites for PTX3 on FH. The primary binding site is located on FH domains 19-20, which interact with the N-terminal domain of PTX3, while a secondary binding site on domain 7 binds the glycosylated PTX3 pentraxin domain. The FH Y402H polymorphism, which affects binding to the short pentraxin CRP, did not affect binding to PTX3. Surface-bound PTX3 enhances FH recruitment and iC3b deposition and PTX3-bound FH retains its activity as a cofactor for factor I-mediated C3b cleavage. Thus, our findings identify PTX3 as a unique FH ligand in that it can bind both of the two hot-spots of FH, namely SCR7 and SCR19-20 and indicate that PTX3 participates in the localization of functionally active FH.

Role of Probiotics in Stimulating the Immune System in Viral Respiratory Tract Infections: A Narrative Review.

Viral respiratory tract infection (RTI) is the most frequent cause of infectious illnesses including the common cold. Pharmacological solutions for treating or preventing viral RTIs are so far limited and thus several self-care products are available in the market. Some dietary supplements such as probiotics have been shown to modulate immune system function and their role in reducing the risk and the course of RTIs has been investigated extensively within the past decade. However, the mechanism of action and the efficacy of probiotics against viral RTIs remains unclear. We searched PubMed, Google Scholar, and Web of Knowledge for pre-clinical and clinical studies investigating the effect of probiotics on respiratory virus infections, immune response, and the course of upper and lower respiratory tract illness. The literature summarized in this narrative review points out that specific probiotic strains seem effective in pre-clinical models, through stimulating the immune system and inhibiting viral replication. Clinical studies indicate variable efficacy on upper respiratory illnesses and lack proof of diagnosed viral infections. However, meta-analyses of clinical studies indicate that probiotics could be beneficial in upper respiratory illnesses without specific etiology. Further studies aiming at discovering the mechanisms of action of probiotics and clinical efficacy are warranted.

Gut Microbiota, Probiotics and Physical Performance in Athletes and Physically Active Individuals.

Among athletes, nutrition plays a key role, supporting training, performance, and post-exercise recovery. Research has primarily focused on the effects of diet in support of an athletic physique; however, the role played by intestinal microbiota has been much neglected. Emerging evidence has shown an association between the intestinal microbiota composition and physical activity, suggesting that modifications in the gut microbiota composition may contribute to physical performance of the host. Probiotics represent a potential means for beneficially influencing the gut microbiota composition/function but can also impact the overall health of the host. In this review, we provide an overview of the existing studies that have examined the reciprocal interactions between physical activity and gut microbiota. We further evaluate the clinical evidence that supports the effects of probiotics on physical performance, post-exercise recovery, and cognitive outcomes among athletes. In addition, we discuss the mechanisms of action through which probiotics affect exercise outcomes. In summary, beneficial microbes, including probiotics, may promote health in athletes and enhance physical performance and exercise capacity. Furthermore, high-quality clinical studies, with adequate power, remain necessary to uncover the roles that are played by gut microbiota populations and probiotics in physical performance and the modes of action behind their potential benefits.

Strain specific stress-modulating effects of candidate probiotics: A systematic screening in a mouse model of chronic restraint stress.

BACKGROUND: Changes in the gut microbiota have been implicated in mood and cognition. In rodents, supplementation with certain bacteria have been shown to alleviate adverse effects of stress on gut microbiota composition and behaviour, but little is known of how the performance of different strains compare to each other. We took a systematic approach to test the efficacy of twelve candidate probiotic strains from ten species/sub-species of Bifidobacterium and Lactobacillus on behaviours and neuroendocrine responses of chronically stressed mice. METHODS: The strains were tested in four screening experiments with non-stressed and chronically stressed vehicle groups. The three most efficacious strains were re-tested to validate the results. Mice were administered a daily oral gavage containing either 1 × 109 colony forming units (CFU) of selected candidate probiotic or saline solution for one week prior to and for three weeks during daily chronic restraint stress. Behavioural tests including the elevated plus maze, open field, novel object recognition, and forced swim test were applied during week five. Corticosterone and adrenocorticotropic hormone (ACTH) were analysed to measure the neuroendocrine response to stress. Plasma and tissue samples were collected for biomarker analyses. RESULTS: Of the twelve candidate probiotics, Lactobacillus paracasei Lpc-37, Lactobacillus plantarum LP12407, Lactobacillus plantarum LP12418 and Lactobacillus plantarum LP12151 prevented stress-associated anxiety and depression-related behaviours from developing compared with chronically stressed vehicle mice. In addition, Lpc-37 improved cognition. CONCLUSION: This systematic screening indicates species- and strain-dependent effects on behavioural outcomes related to stress and further suggests that strains differ from each other in their effects on potential mechanistic outcomes.

Bifidobacterium animalis subsp. lactis 420 for Metabolic Health: Review of the Research.

The growing worldwide epidemic of obesity and associated metabolic health comorbidities has resulted in an urgent need for safe and efficient nutritional solutions. The research linking obesity with gut microbiota dysbiosis has led to a hypothesis that certain bacterial strains could serve as probiotics helping in weight management and metabolic health. In the search for such strains, the effect of Bifidobacterium animalis subsp. lactis 420 (B420) on gut microbiota and metabolic health, and the mechanisms of actions, has been investigated in a variety of in vitro, pre-clinical, and clinical studies. In this review, we aim to highlight the research on B420 related to obesity, metabolic health, and the microbiota. Current research supports the hypothesis that gut dysbiosis leads to an imbalance in the inflammatory processes and loss of epithelial integrity. Bacterial components, like endotoxins, that leak out of the gut can invoke low-grade, chronic, and systemic inflammation. This imbalanced state is often referred to as metabolic endotoxemia. Scientific evidence indicates that B420 can slow down many of these detrimental processes via multiple signaling pathways, as supported by mechanistic in vitro and in vivo studies. We discuss the connection of these mechanisms to clinical evidence on the effect of B420 in controlling weight gain in overweight and obese subjects. The research further indicates that B420 may improve the epithelial integrity by rebalancing a dysbiotic state induced by an obesogenic diet, for example by increasing the prevalence of lean phenotype microbes such as Akkermansia muciniphila. We further discuss, in the context of delivering the health benefits of B420: the safety and technological aspects of the strain including genomic characterization, antibiotic resistance profiling, stability in the product, and survival of the live probiotic in the intestine. In summary, we conclude that the clinical and preclinical studies on metabolic health suggest that B420 may be a potential candidate in combating obesity; however, further clinical studies are needed.

T-bet+ Memory B Cells Link to Local Cross-Reactive IgG upon Human Rhinovirus Infection.

Human rhinoviruses cause the common cold and exacerbate chronic respiratory diseases. Although infection elicits neutralizing antibodies, these do not persist or cross-protect across multiple rhinovirus strains. To analyze rhinovirus-specific B cell responses in humans, we developed techniques using intact RV-A16 and RV-A39 for high-throughput high-dimensional single-cell analysis, with parallel assessment of antibody isotypes in an experimental infection model. Our approach identified T-bet+ B cells binding both viruses that account for ∼5% of CXCR5- memory B cells. These B cells infiltrate nasal tissue and expand in the blood after infection. Their rapid secretion of heterotypic immunoglobulin G (IgG) in vitro, but not IgA, matches the nasal antibody profile post-infection. By contrast, CXCR5+ memory B cells binding a single virus are clonally distinct, absent in nasal tissue, and secrete homotypic IgG and IgA, mirroring the systemic response. Temporal and spatial functions of dichotomous memory B cells might explain the ability to resolve infection while rendering the host susceptible to re-infection.