-
Gut Microbes 2022Gut microbial disturbance affects allergic diseases including asthma, atopic dermatitis (AD) via the aberrant immune response. Some Bifidobacterial species and strains...
Gut microbial disturbance affects allergic diseases including asthma, atopic dermatitis (AD) via the aberrant immune response. Some Bifidobacterial species and strains have been reported to improve AD via modulating immune-microbe interactions in patients. However, the effective metabolites and mechanism of alleviating AD in bifidobacteria remain to be elucidated. This study aimed to explore the microbial metabolite and mechanism of to improve AD. Based on shotgun metagenomic sequencing and UHPLC Q-Exactive-MS targeted metabolic experiments and , we focused on tryptophan metabolism and indole derivatives, which are endogenous ligands for aryl hydrocarbon receptor (AHR). Indole-3-carbaldehyde (I3C), a tryptophan metabolite of CCFM1029 activated AHR-mediated immune signaling pathway to improve AD symptoms in animal and clinical experiments. CCFM1029 upregulated tryptophan metabolism and increased I3C to suppress aberrant T helper 2 type immune responses, but these benefits were eliminated by AHR antagonist CH223191. Furthermore, CCFM1029 reshaped gut microbial composition in AD patients, increased fecal and serum I3C, and maintained the abundance of related to tryptophan metabolism of gut microbiota. The results suggested that based on the interactions of the gut-skin axis, CCFM1029 upregulated tryptophan metabolism and produced I3C to activate AHR-mediated immune response, alleviating AD symptoms. Indole derivates, microbial metabolites of tryptophan, may be the potential metabolites of bifidobacteria to alleviate AD via the AHR signaling pathway.
Topics: Animals; Bifidobacterium; Bifidobacterium longum; Dermatitis, Atopic; Gastrointestinal Microbiome; Humans; Indoles; Receptors, Aryl Hydrocarbon; Tryptophan
PubMed: 35239463
DOI: 10.1080/19490976.2022.2044723 -
Nature Microbiology Nov 2021Breastfeeding profoundly shapes the infant gut microbiota, which is critical for early life immune development, and the gut microbiota can impact host physiology in... (Observational Study)
Observational Study
Breastfeeding profoundly shapes the infant gut microbiota, which is critical for early life immune development, and the gut microbiota can impact host physiology in various ways, such as through the production of metabolites. However, few breastmilk-dependent microbial metabolites mediating host-microbiota interactions are currently known. Here, we demonstrate that breastmilk-promoted Bifidobacterium species convert aromatic amino acids (tryptophan, phenylalanine and tyrosine) into their respective aromatic lactic acids (indolelactic acid, phenyllactic acid and 4-hydroxyphenyllactic acid) via a previously unrecognized aromatic lactate dehydrogenase (ALDH). The ability of Bifidobacterium species to convert aromatic amino acids to their lactic acid derivatives was confirmed using monocolonized mice. Longitudinal profiling of the faecal microbiota composition and metabolome of Danish infants (n = 25), from birth until 6 months of age, showed that faecal concentrations of aromatic lactic acids are correlated positively with the abundance of human milk oligosaccharide-degrading Bifidobacterium species containing the ALDH, including Bifidobacterium longum, B. breve and B. bifidum. We further demonstrate that faecal concentrations of Bifidobacterium-derived indolelactic acid are associated with the capacity of these samples to activate in vitro the aryl hydrocarbon receptor (AhR), a receptor important for controlling intestinal homoeostasis and immune responses. Finally, we show that indolelactic acid modulates ex vivo immune responses of human CD4 T cells and monocytes in a dose-dependent manner by acting as an agonist of both the AhR and hydroxycarboxylic acid receptor 3 (HCA). Our findings reveal that breastmilk-promoted Bifidobacterium species produce aromatic lactic acids in the gut of infants and suggest that these microbial metabolites may impact immune function in early life.
Topics: Adult; Animals; Bacteria; Bifidobacterium; Breast Feeding; Cohort Studies; Feces; Female; Gastrointestinal Microbiome; Humans; Infant; Lactic Acid; Male; Mice; Receptors, Aryl Hydrocarbon; Young Adult
PubMed: 34675385
DOI: 10.1038/s41564-021-00970-4 -
Cell Nov 2022The gut microbiome has an important role in infant health and development. We characterized the fecal microbiome and metabolome of 222 young children in Dhaka,...
The gut microbiome has an important role in infant health and development. We characterized the fecal microbiome and metabolome of 222 young children in Dhaka, Bangladesh during the first two years of life. A distinct Bifidobacterium longum clade expanded with introduction of solid foods and harbored enzymes for utilizing both breast milk and solid food substrates. The clade was highly prevalent in Bangladesh, present globally (at lower prevalence), and correlated with many other gut taxa and metabolites, indicating an important role in gut ecology. We also found that the B. longum clades and associated metabolites were implicated in childhood diarrhea and early growth, including positive associations between growth measures and B. longum subsp. infantis, indolelactate and N-acetylglutamate. Our data demonstrate geographic, cultural, seasonal, and ecological heterogeneity that should be accounted for when identifying microbiome factors implicated in and potentially benefiting infant development.
Topics: Infant; Child; Female; Humans; Child, Preschool; Bifidobacterium longum; Bifidobacterium; Weaning; Oligosaccharides; Bangladesh; Milk, Human; Feces
PubMed: 36323316
DOI: 10.1016/j.cell.2022.10.011 -
Frontiers in Cellular and Infection... 2022To investigate the effect of B94 on the prevention and treatment of liver injury in rats and to elucidate the underlying mechanism of this relationship.
OBJECTIVE
To investigate the effect of B94 on the prevention and treatment of liver injury in rats and to elucidate the underlying mechanism of this relationship.
METHODS
Specific pathogen-free (SPF) rats were selected as the healthy control group, liver injury group and B94 treatment group, with 6 rats in each group. After the model was established, the experimental animals were tested for serum liver function indicators, gut microbiota composition, metabolite composition, and histopathology.
RESULTS
The albumin/globulin ratio and serum TBA, alanine aminotransferase, aspartate aminotransferase, and indirect bilirubin levels in the B94 treatment group were significantly lower than those in the liver injury group. 16S rRNA analysis showed that the gut microbiota of the three groups of rats were significantly different. Metabolic profile analysis showed that there were significant differences in the gut metabolomes of the three groups. Haematoxylin-eosin staining of the intestinal mucosa and liver tissues showed that the degree of liver and intestinal tissue damage in the B94 treatment group was significantly lower than that in the liver injury group.
CONCLUSION
B94 can affect the process of liver injury in rats by improving liver function, reducing intestinal damage, and regulating gut microbiota and metabolite production.
Topics: Animals; Bifidobacterium; Bifidobacterium animalis; Liver; Probiotics; RNA, Ribosomal, 16S; Rats
PubMed: 35846768
DOI: 10.3389/fcimb.2022.914684 -
Molecules (Basel, Switzerland) Jul 2022Expression and purification of β-galactosidases derived from provide a new resource for efficient lactose hydrolysis and lactose intolerance alleviation. Here, we...
Expression and purification of β-galactosidases derived from provide a new resource for efficient lactose hydrolysis and lactose intolerance alleviation. Here, we cloned and expressed two β-galactosidases derived from . The optimal pH for BLGLB1 was 5.5, and the optimal temperature was 45 °C, at which the enzyme activity of BLGLB1 was higher than that of commercial enzyme E (300 ± 3.6 U/mg) under its optimal conditions, reaching 2200 ± 15 U/mg. The optimal pH and temperature for BPGLB1 were 6.0 and 45 °C, respectively, and the enzyme activity (0.58 ± 0.03 U/mg) under optimum conditions was significantly lower than that of BLGLB1. The structures of the two β-galactosidase were similar, with all known key sites conserved. When o-nitrophenyl-β-D-galactoside (oNPG) was used as an enzyme reaction substrate, the maximum reaction velocity () for BLGLB1 and BPGLB1 was 3700 ± 100 U/mg and 1.1 ± 0.1 U/mg, respectively. The kinetic constant () of BLGLB1 and BPGLB1 was 1.9 ± 0.1 and 1.3 ± 0.3 mmol/L, respectively. The respective catalytic constant () of BLGLB1 and BPGLB1 was 1700 ± 40 s and 0.5 ± 0.02 s, respectively; the respective / value of BLGLB1 and BPGLB1 was 870 L/(mmol∙s) and 0.36 L/(mmol∙s), respectively. The , and values of BLGLB1 were superior to those of earlier reported β-galactosidase derived from . Overall, BLGLB1 has potential application in the food industry.
Topics: Bifidobacterium; Bifidobacterium longum; Bifidobacterium pseudocatenulatum; Cloning, Molecular; Hydrogen-Ion Concentration; Kinetics; Lactose; Temperature; beta-Galactosidase
PubMed: 35889370
DOI: 10.3390/molecules27144497 -
International Journal of Molecular... May 2018Over the past decade, a variety of lactic acid bacteria have been commercially available to and steadily used by consumers. However, recent studies have shown that some...
Over the past decade, a variety of lactic acid bacteria have been commercially available to and steadily used by consumers. However, recent studies have shown that some lactic acid bacteria produce toxic substances and display properties of virulence. To establish safety guidelines for lactic acid bacteria, the Food and Agriculture Organization of the United Nations (FAO)/World Health Organization (WHO) has suggested that lactic acid bacteria be characterized and proven safe for consumers’ health via multiple experiments (e.g., antibiotic resistance, metabolic activity, toxin production, hemolytic activity, infectivity in immune-compromised animal species, human side effects, and adverse-outcome analyses). Among the lactic acid bacteria, and species are probiotic strains that are most commonly commercially produced and actively studied. BGN4 and BORI have been used in global functional food markets (e.g., China, Germany, Jordan, Korea, Lithuania, New Zealand, Poland, Singapore, Thailand, Turkey, and Vietnam) as nutraceutical ingredients for decades, without any adverse events. However, given that the safety of some newly screened probiotic species has recently been debated, it is crucial that the consumer safety of each commercially utilized strain be confirmed. Accordingly, this paper details a safety assessment of BGN4 and BORI via the assessment of ammonia production, hemolysis of blood cells, biogenic amine production, antimicrobial susceptibility pattern, antibiotic resistance gene transferability, PCR data on antibiotic resistance genes, mucin degradation, genome stability, and possession of virulence factors. These probiotic strains showed neither hemolytic activity nor mucin degradation activity, and they did not produce ammonia or biogenic amines (i.e., cadaverine, histamine or tyramine). BGN4 and BORI produced a small amount of putrescine, commonly found in living cells, at levels similar to or lower than that found in other foods (e.g., spinach, ketchup, green pea, sauerkraut, and sausage). BGN4 showed higher resistance to gentamicin than the European Food Safety Authority (EFSA) cut-off. However, this paper shows the gentamicin resistance of BGN4 was not transferred via conjugation with ATCC 4356, the latter of which is highly susceptible to gentamicin. The entire genomic sequence of BGN4 has been published in GenBank (accession no.: CP001361.1), documenting the lack of retention of plasmids capable of transferring an antibiotic-resistant gene. Moreover, there was little genetic mutation between the first and 25th generations of BGN4. Tetracycline-resistant genes are prevalent among strains; BORI has a (W) gene on its chromosome DNA and has also shown resistance to tetracycline. However, this research shows that its tetracycline resistance was not transferred via conjugation with AGBG1, the latter of which is highly sensitive to tetracycline. These findings support the continuous use of BGN4 and BORI as probiotics, both of which have been reported as safe by several clinical studies, and have been used in food supplements for many years.
Topics: Ammonia; Animals; Anti-Bacterial Agents; Bifidobacterium bifidum; Bifidobacterium longum; Biogenic Amines; Drug Resistance, Microbial; Hemolysis; Humans; Microbial Sensitivity Tests; Virulence Factors
PubMed: 29747442
DOI: 10.3390/ijms19051422 -
Critical Reviews in Biochemistry and... 2022Bifidobacteria are early colonizers of the human neonatal gut and provide multiple health benefits to the infant, including inhibiting the growth of enteropathogens and... (Review)
Review
Bifidobacteria are early colonizers of the human neonatal gut and provide multiple health benefits to the infant, including inhibiting the growth of enteropathogens and modulating the immune system. Certain species prevail in the gut of breastfed infants due to the ability of these microorganisms to selectively forage glycans present in human milk, specifically human milk oligosaccharides (HMOs) and -linked glycans. Therefore, these carbohydrates serve as promising prebiotic dietary supplements to stimulate the growth of bifidobacteria in the guts of children suffering from impaired gut microbiota development. However, the rational formulation of milk glycan-based prebiotics requires a detailed understanding of how bifidobacteria metabolize these carbohydrates. Accumulating biochemical and genomic data suggest that HMO and -glycan assimilation abilities vary remarkably within the genus, both at the species and strain levels. This review focuses on the delineation and genome-based comparative analysis of differences in respective biochemical pathways, transport systems, and associated transcriptional regulatory networks, providing a foundation for genomics-based projection of milk glycan utilization capabilities across a rapidly growing number of sequenced bifidobacterial genomes and metagenomic datasets. This analysis also highlights remaining knowledge gaps and suggests directions for future studies to optimize the formulation of milk-glycan-based prebiotics that target bifidobacteria.
Topics: Infant; Infant, Newborn; Child; Humans; Bifidobacterium; Prebiotics; Milk, Human; Polysaccharides; Carbohydrates; Genomics
PubMed: 36866565
DOI: 10.1080/10409238.2023.2182272 -
Current Microbiology Feb 2022Aging is an irreversible physiological degradation of living organisms. Accumulated oxidative stress and dysbiosis accelerate aging. Probiotics such as Lactobacillus and...
Aging is an irreversible physiological degradation of living organisms. Accumulated oxidative stress and dysbiosis accelerate aging. Probiotics such as Lactobacillus and Bifidobacterium and their fermented metabolites (postbiotics) have been discovered to exhibit antioxidative activities that regulate oxidative stress and protect cells from oxidative damage. We screened selected Lactobacillus and Bifidobacterium strains and their postbiotics for potential antioxidative activity by using DPPH (2,2-Diphenyl-1-picrylhydrazyl) assay. Strains with their metabolites were selected for mixed formula in experiments involving aging mice. The aged groups presented higher oxidative stress in the brain, liver, heart, and kidney than did young mice. However, treatment with probiotic strains and their postbiotics elevated antioxidative levels, especially in the high-dose probiotics plus postbiotics group. Next-generation sequencing data revealed positive microbiota alterations of Lactobacillus and Bifidobacterium and Akkermansia in the gut. Lactobacillus johnsonii and Akkermansia muciniphila exhibited effective enlargement of relative abundance. Besides, high-dose probiotics and high-dose probiotics plus postbiotics showed significant elevation in serum SCFAs, especially in butyrate. In conclusion, the formula containing Bifidobacterium animalis subsp. infantis BLI-02, Bifidobacterium breve Bv889, Bifidobacterium bifidum VDD088, B. animalis subsp. lactis CP-9, and Lactobacillus plantarum PL-02 and their metabolites may benefit aged people's health.
Topics: Animals; Bifidobacterium; Bifidobacterium bifidum; Lactobacillus; Mice; Oxidative Stress; Probiotics
PubMed: 35157139
DOI: 10.1007/s00284-022-02783-y -
Nature Communications Jul 2023Although compositional variation in the gut microbiome during human development has been extensively investigated, strain-resolved dynamic changes remain to be fully... (Meta-Analysis)
Meta-Analysis
Although compositional variation in the gut microbiome during human development has been extensively investigated, strain-resolved dynamic changes remain to be fully uncovered. In the current study, shotgun metagenomic sequencing data of 12,415 fecal microbiomes from healthy individuals are employed for strain-level tracking of gut microbiota members to elucidate its evolving biodiversity across the human life span. This detailed longitudinal meta-analysis reveals host sex-related persistence of strains belonging to common, maternally-inherited species, such as Bifidobacterium bifidum and Bifidobacterium longum subsp. longum. Comparative genome analyses, coupled with experiments including intimate interaction between microbes and human intestinal cells, show that specific bacterial glycosyl hydrolases related to host-glycan metabolism may contribute to more efficient colonization in females compared to males. These findings point to an intriguing ancient sex-specific host-microbe coevolution driving the selective persistence in women of key microbial taxa that may be vertically passed on to the next generation.
Topics: Male; Humans; Female; Gastrointestinal Microbiome; Bifidobacterium; Microbiota; Bacteria
PubMed: 37452041
DOI: 10.1038/s41467-023-39931-2 -
Nature Microbiology Oct 2022The development of the gut microbiome from birth plays important roles in short- and long-term health, but factors influencing preterm gut microbiome development are...
The development of the gut microbiome from birth plays important roles in short- and long-term health, but factors influencing preterm gut microbiome development are poorly understood. In the present study, we use metagenomic sequencing to analyse 1,431 longitudinal stool samples from 123 very preterm infants (<32 weeks' gestation) who did not develop intestinal disease or sepsis over a study period of 10 years. During the study period, one cohort had no probiotic exposure whereas two cohorts were given different probiotic products: Infloran (Bifidobacterium bifidum and Lactobacillus acidophilus) or Labinic (B. bifidum, B. longum subsp. infantis and L. acidophilus). Mothers' own milk, breast milk fortifier, antibiotics and probiotics were significantly associated with the gut microbiome, with probiotics being the most significant factor. Probiotics drove microbiome transition into different preterm gut community types (PGCTs), each enriched in a different Bifidobacterium sp. and significantly associated with increased postnatal age. Functional analyses identified stool metabolites associated with PGCTs and, in preterm-derived organoids, sterile faecal supernatants impacted intestinal, organoid monolayer, gene expression in a PGCT-specific manner. The present study identifies specific influencers of gut microbiome development in very preterm infants, some of which overlap with those impacting term infants. The results highlight the importance of strain-specific differences in probiotic products and their impact on host interactions in the preterm gut.
Topics: Anti-Bacterial Agents; Bifidobacterium; Bifidobacterium bifidum; Female; Gastrointestinal Microbiome; Humans; Infant; Infant, Newborn; Infant, Premature; Probiotics
PubMed: 36163498
DOI: 10.1038/s41564-022-01213-w