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Frontiers in Nutrition 2022Human milk oligosaccharides (HMOs) have important biological functions for a healthy development in early life.
Infant Formula With a Specific Blend of Five Human Milk Oligosaccharides Drives the Gut Microbiota Development and Improves Gut Maturation Markers: A Randomized Controlled Trial.
BACKGROUND
Human milk oligosaccharides (HMOs) have important biological functions for a healthy development in early life.
OBJECTIVE
This study aimed to investigate gut maturation effects of an infant formula containing five HMOs (2'-fucosyllactose, 2',3-di-fucosyllactose, lacto-N-tetraose, 3'-sialyllactose, and 6'-sialyllactose).
METHODS
In a multicenter study, healthy infants (7-21 days old) were randomly assigned to a standard cow's milk-based infant formula (control group, CG); the same formula with 1.5 g/L HMOs (test group 1, TG1); or with 2.5 g/L HMOs (test group 2, TG2). A human milk-fed group (HMG) was enrolled as a reference. Fecal samples collected at baseline (∼150/formula group; HMG = 60), age 3 (∼140/formula group; HMG = 65) and 6 (∼115/formula group; HMG = 60) months were analyzed for microbiome (shotgun metagenomics), metabolism, and biomarkers.
RESULTS
At both post-baseline visits, weighted UniFrac analysis indicated different microbiota compositions in the two test groups (TGs) compared to CG ( < 0.01) with coordinates closer to that of HMG. The relative abundance of subsp. () was higher in TGs vs. CG ( < 0.05; except at 6 months: TG2 vs. CG = 0.083). abundance was higher by ∼45% in TGs vs. CG at 6-month approaching HMG. At both post-baseline visits, toxigenic abundance was 75-85% lower in TGs vs. CG ( < 0.05) and comparable with HMG. Fecal pH was significantly lower in TGs vs. CG, and the overall organic acid profile was different in TGs vs. CG, approaching HMG. At 3 months, TGs (vs. CG) had higher secretory immunoglobulin A (sIgA) and lower alpha-1-antitrypsin ( < 0.05). At 6 months, sIgA in TG2 vs. CG remained higher ( < 0.05), and calprotectin was lower in TG1 ( < 0.05) vs. CG.
CONCLUSION
Infant formula with a specific blend of five HMOs supports the development of the intestinal immune system and gut barrier function and shifts the gut microbiome closer to that of breastfed infants with higher bifidobacteria, particularly , and lower toxigenic .
CLINICAL TRIAL REGISTRATION
[https://clinicaltrials.gov/ct2/show/], identifier [NCT03722550].
PubMed: 35873420
DOI: 10.3389/fnut.2022.920362 -
Nature Communications Oct 2021Understanding the functional potential of the gut microbiome is of primary importance for the design of innovative strategies for allergy treatment and prevention. Here... (Clinical Trial)
Clinical Trial
Understanding the functional potential of the gut microbiome is of primary importance for the design of innovative strategies for allergy treatment and prevention. Here we report the gut microbiome features of 90 children affected by food (FA) or respiratory (RA) allergies and 30 age-matched, healthy controls (CT). We identify specific microbial signatures in the gut microbiome of allergic children, such as higher abundance of Ruminococcus gnavus and Faecalibacterium prausnitzii, and a depletion of Bifidobacterium longum, Bacteroides dorei, B. vulgatus and fiber-degrading taxa. The metagenome of allergic children shows a pro-inflammatory potential, with an enrichment of genes involved in the production of bacterial lipo-polysaccharides and urease. We demonstrate that specific gut microbiome signatures at baseline can be predictable of immune tolerance acquisition. Finally, a strain-level selection occurring in the gut microbiome of allergic subjects is identified. R. gnavus strains enriched in FA and RA showed lower ability to degrade fiber, and genes involved in the production of a pro-inflammatory polysaccharide. We demonstrate that a gut microbiome dysbiosis occurs in allergic children, with R. gnavus emerging as a main player in pediatric allergy. These findings may open new strategies in the development of innovative preventive and therapeutic approaches. Trial: NCT04750980.
Topics: Allergens; Animals; Bacteroides; Bifidobacterium longum; Case-Control Studies; Child; Child, Preschool; Clostridiales; Dander; Eggs; Faecalibacterium prausnitzii; Female; Food Hypersensitivity; Gastrointestinal Microbiome; Humans; Immune Tolerance; Lipopolysaccharides; Male; Milk; Nuts; Pollen; Prunus persica; Pyroglyphidae; Respiratory Hypersensitivity; Urease
PubMed: 34645820
DOI: 10.1038/s41467-021-26266-z -
Allergy, Asthma & Immunology Research Sep 2022The beneficial effects of a combination therapy using and galactooligosaccharide (GOS) for the treatment of atopic dermatitis (AD) have not been elucidated.
PURPOSE
The beneficial effects of a combination therapy using and galactooligosaccharide (GOS) for the treatment of atopic dermatitis (AD) have not been elucidated.
METHODS
Gene expressions of interleukin (IL)-4 and IL-13 from peripheral blood mononuclear cells and fecal abundance of . from 12-month-old infants were evaluated. Human primary epidermal keratinocytes (HEKs) and hairless mice were treated with , GOS, -derived extracellular vesicles (BLEVs), dinitrochlorobenzene (DNCB), or a synbiotic mixture of . and GOS. Expression of epidermal barrier proteins and cytokines as well as serum immunoglobulin E (IgE) levels were analyzed in HEKs and mice. Dermatitis scores, transepidermal water loss (TEWL), epidermal thickness, and fecal abundance were evaluated in mice.
RESULTS
Fecal abundance of . was negatively correlated with blood expression in infants. or BLEVs increased expression of filaggrin () and loricrin () in HEKs. . increased the efficacy of GOS to upregulate and expressions in HEKs. Oral administration of GOS increased fecal abundance of . in mice. Oral administration of . attenuated DNCB-induced skin inflammation, abnormal TEWL, AD-like skin, and deficiency of epidermal barrier proteins. Moreover, the combination of and GOS showed greater effects to improve DNCB-induced skin inflammation, abnormal TEWL, AD-like skin, serum IgE levels, over-expression, and the deficiency of epidermal barrier proteins than the administration of alone.
CONCLUSIONS
and GOS improve DNCB-induced skin barrier dysfunction and AD-like skin.
PubMed: 36174995
DOI: 10.4168/aair.2022.14.5.549 -
Frontiers in Microbiology 2021Members of the genus , of which the majority have been isolated as gut commensals, are Gram-positive, non-motile, saccharolytic, non-sporulating, anaerobic bacteria.... (Review)
Review
Members of the genus , of which the majority have been isolated as gut commensals, are Gram-positive, non-motile, saccharolytic, non-sporulating, anaerobic bacteria. Many bifidobacterial strains are considered probiotic and therefore are thought to bestow health benefits upon their host. Bifidobacteria are highly abundant among the gut microbiota of healthy, full term, breast-fed infants, yet the relative average abundance of bifidobacteria tends to decrease as the human host ages. Because of the inverse correlation between bifidobacterial abundance/prevalence and health, there has been an increasing interest in maintaining, increasing or restoring bifidobacterial populations in the infant, adult and elderly gut. In order to colonize and persist in the gastrointestinal environment, bifidobacteria must be able to metabolise complex dietary and/or host-derived carbohydrates, and be resistant to various environmental challenges of the gut. This is not only important for the autochthonous bifidobacterial species colonising the gut, but also for allochthonous bifidobacteria provided as probiotic supplements in functional foods. For example, subsp. is a taxon associated with the metabolism of plant-derived poly/oligosaccharides in the adult diet, being capable of metabolising hemicellulose and various pectin-associated glycans. Many of these plant glycans are believed to stimulate the metabolism and growth of specific bifidobacterial species and are for this reason classified as prebiotics. In this review, bifidobacterial carbohydrate metabolism, with a focus on plant poly-/oligosaccharide degradation and uptake, as well as its associated regulation, will be discussed.
PubMed: 33613480
DOI: 10.3389/fmicb.2021.609418 -
PloS One 2023Osteoarthritis (OA), the most common form of arthritis, is characterized by pain and cartilage damage; it usually exhibits gradual development. However, the pathogenesis...
Osteoarthritis (OA), the most common form of arthritis, is characterized by pain and cartilage damage; it usually exhibits gradual development. However, the pathogenesis of OA remains unclear. This study was undertaken to improve the understanding and treatment of OA. OA was induced in 7-week-old Wistar rats by intra-articular injection of monosodium iodoacetate (MIA); subsequently, the rats underwent oral administration of Bifidobacterium longum BORI (B. BORI). The effects of B. BORI were examined in chondrocytes and an MIA-induced OA rat model. In the rats, B. BORI-mediated effects on pain severity, cartilage destruction, and inflammation were recorded. Additional effects on mRNA and cytokine secretion were analyzed by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Paw withdrawal threshold, paw withdrawal latency, and weight-bearing assessments revealed that pain severity in MIA-induced OA rats was decreased after B. BORI treatment. Histopathology analyses and three-dimensional surface renderings of rat femurs from micro-computed tomography images revealed cartilage protection and cartilage loss inhibition effects in B. BORI-treated OA rats. Immunohistochemical analyses of inflammatory cytokines and catabolic markers (e.g., matrix metalloproteinases) showed that the expression levels of both were reduced in tissue from B. BORI-treated OA rats. Furthermore, B. BORI treatment decreased the expression levels of the inflammatory cytokine monocyte chemoattractant protein-1 and inflammatory gene factors (e.g., inflammatory cell death markers) in chondrocytes. The findings indicate that oral administration of B. BORI has therapeutic potential in terms of reducing pain, progression, and inflammation in OA.
Topics: Rats; Animals; Chondrocytes; Rats, Wistar; X-Ray Microtomography; Cartilage, Articular; Osteoarthritis; Pain; Inflammation; Iodoacetic Acid; Cytokines
PubMed: 37352198
DOI: 10.1371/journal.pone.0286456 -
Sovremennye Tekhnologii V Meditsine 2022was to analyze the genome features of the probiotic strains 379, 1, and 791 and study their antiviral activity.
UNLABELLED
was to analyze the genome features of the probiotic strains 379, 1, and 791 and study their antiviral activity.
MATERIALS AND METHODS
Whole genome sequencing of three strains of bifidobacteria was performed on the MiSeq platform (Illumina Inc., USA). The genomes were annotated using the Prokka v. 1.11 utility and RAST genomic server. The individual genetic determinants were searched using the ResFinder 3.2, PathogenFinder, PlasmidFinder, RAST, and Bagel 4 software. The antiviral activity of the strains against influenza A viruses was studied using MDCK cells (Madin-Darby canine kidney cells), the epidemic strain of influenza A/Lipetsk/1V/2018 (H1N1 pdm09) (EPI_ISL_332798), the highly pathogenic avian influenza virus A/common gull/Saratov/1676/2018 (H5N6) strain (EPI_ISL_336925), and neutral red vital dye.
RESULTS
The genomes of all studied strains contained determinants responsible for utilization of carbohydrates of plant origin; the genes of key enzymes for the synthesis of tryptophan and folic acid are present in the genomes of 379 and 791. A feature of the 791 genome is the presence of determinants responsible for the synthesis of thermostable type I bacteriocins - flavucin and lasso peptide. The 791 strain was found to show pronounced antiviral activity against both the strains of influenza A, the supernatant of which suppressed viral replication up to a dilution of 1:8, and the cells inhibited viral reproduction up to a concentration of 6·106 CFU/ml.
CONCLUSION
The analysis of complete genomes of 379, 1, and 791 showed features that determine their strain-specific properties, the findings on which were previously made empirically based on indirect signs. In the genomes of 379 and 791 strains, in contrast to 1 strain, key enzymes for the synthesis of tryptophan and folic acid were found. These substances have an impact on the human body in many ways, including having a thymoleptic effect (reducing emotional stress, irritability, anxiety, eliminating lethargy, apathy, melancholy, anxiety) and regulating cognitive activity. The presence of determinants responsible for the synthesis of thermostable type I bacteriocins in the genome of 791 strain determines its pronounced antiviral activity.
Topics: Animals; Dogs; Humans; Bifidobacterium; Influenza A Virus, H1N1 Subtype; Influenza, Human; Tryptophan; Probiotics; Bifidobacterium bifidum; Bacteriocins; Antiviral Agents; Folic Acid
PubMed: 37181836
DOI: 10.17691/stm2022.14.5.04 -
International Journal of Molecular... Dec 2022are prominent gut commensals that produce the short-chain fatty acid (SCFA) acetate, and they are often used as probiotics. Connections between the gut and the lung,...
are prominent gut commensals that produce the short-chain fatty acid (SCFA) acetate, and they are often used as probiotics. Connections between the gut and the lung, termed the gut-lung axis, are regulated by the microbiome. The gut-lung axis is increasingly implicated in cigarette smoke-induced diseases, and cigarette smoke exposure has been associated with depletion of species. In this study, we assessed the impact of acetate-producing subsp. (WT) and a mutant strain with an impaired acetate production capacity (MUT) on cigarette smoke-induced inflammation. The mice were treated with WT or MUT subsp. and exposed to cigarette smoke for 8 weeks before assessments of lung inflammation, lung tissue gene expression and cecal SCFAs were performed. Both strains of subsp. reduced lung inflammation, inflammatory cytokine expression and adhesion factor expression and alleviated cigarette smoke-induced depletion in caecum butyrate. Thus, the probiotic administration of subsp. irrespective of its acetate-producing capacity, alleviated cigarette smoke-induced inflammation and the depletion of cecal butyrate levels.
Topics: Mice; Animals; Cigarette Smoking; Bifidobacterium; Probiotics; Butyrates; Acetates; Inflammation
PubMed: 36613693
DOI: 10.3390/ijms24010252 -
Trends in Microbiology Oct 2022Bifidobacteria are among the earliest and most abundant bacterial colonizers of the neonatal gut in many mammals, where they elicit purported host health benefits. While... (Review)
Review
Bifidobacteria are among the earliest and most abundant bacterial colonizers of the neonatal gut in many mammals, where they elicit purported host health benefits. While early life-associated dynamics and diversity, as well as the metabolic and beneficial activities, of Bifidobacterium species have been well studied, functional contributions of bifidobacteria to health and well-being of adults remain less explored. In this opinion piece, we discuss the current knowledge regarding the relevance of endogenous Bifidobacterium species associated with adulthood. We identify knowledge gaps and discuss opportunities for microbiota enrichment with rationally selected strains of Bifidobacterium more adapted to the adult host. We propose that current knowledge and future studies in this area will help us to better understand the ecological, metabolic, and functional roles played by Bifidobacterium in the gut ecosystem across various host ages.
Topics: Adult; Animals; Bacteria; Bifidobacterium; Gastrointestinal Microbiome; Humans; Infant, Newborn; Mammals; Microbiota
PubMed: 35577716
DOI: 10.1016/j.tim.2022.04.004 -
Gut Microbes 2023The significance of to human health can be appreciated from its early colonization of the neonatal gut, where represents the most abundant species. While its relative... (Review)
Review
The significance of to human health can be appreciated from its early colonization of the neonatal gut, where represents the most abundant species. While its relative abundance declines with age, it is further reduced in several diseases. Research into the beneficial properties of has unveiled a range of mechanisms, including the production of bioactive molecules, such as short-chain fatty acids, polysaccharides, and serine protease inhibitors. From its intestinal niche, can have far-reaching effects in the body influencing immune responses in the lungs and even skin, as well as influencing brain activity. In this review, we present the biological and clinical impacts of this species on a range of human conditions beginning in neonatal life and beyond. The available scientific evidence reveals a strong rationale for continued research and further clinical trials that investigate the ability of to treat or prevent a range of diseases across the human lifespan.
Topics: Infant, Newborn; Humans; Bifidobacterium longum; Gastrointestinal Microbiome; Bifidobacterium; Fatty Acids, Volatile; Probiotics
PubMed: 36896934
DOI: 10.1080/19490976.2023.2186098 -
Free Radical Biology & Medicine Jul 2023Acetaminophen (APAP) overdose is the most common driver of drug-induced liver injury (DILI) worldwide, and the gut microbiome plays a crucial role in this process. In...
Acetaminophen (APAP) overdose is the most common driver of drug-induced liver injury (DILI) worldwide, and the gut microbiome plays a crucial role in this process. In this study, we estimated the effect of Bifidobacterium longum R0175 on APAP-induced liver injury in mice and discovered that B. longum R0175 alleviated liver injury by diminishing inflammation, reducing oxidative stress levels, inhibiting hepatocyte death and improving APAP-induced microbiome dysbiosis. Further studies revealed that the antioxidative effects of B. longum R0175 were primarily due to activation of the Nrf2 pathway, which was supported by the Nrf2 pathway inhibitor ML385 counteracting these ameliorative effects. B. longum R0175 modified intestinal metabolites, especially the key metabolite sedanolide, which could activate the Nrf2 pathway and contribute to the protective effects against APAP-induced liver injury. Moreover, we found that sedanolide exhibited close interrelationships with specific microbial taxa, indicating that this factor may be derived from gut microbes. In conclusion, our work demonstrated that B. longum R0175 could reduce oxidative damage, inflammation and hepatocyte death by activating the Nrf2 pathway. Importantly, we identified the microbiota-derived metabolite sedanolide, which was first discovered in the mouse intestine, as a key agonist of the Nrf2 pathway and primary effector of B. longum R0175 in APAP challenge. These findings provide new perspectives for APAP overdose therapy and demonstrate the enormous potential of B. longum R0175 in alleviating acute liver injury.
Topics: Mice; Animals; Acetaminophen; NF-E2-Related Factor 2; Chemical and Drug Induced Liver Injury, Chronic; Bifidobacterium longum; Liver; Oxidative Stress; Chemical and Drug Induced Liver Injury; Inflammation; Mice, Inbred C57BL
PubMed: 37003500
DOI: 10.1016/j.freeradbiomed.2023.03.026