Human Breast Milk Promotes the Secretion of Potentially Beneficial Metabolites by Probiotic Lactobacillus reuteri DSM 17938

Human breast milk (HBM) may have beneficial effects on Lactobacillus reuteri DSM 17938 (LR 17938) -mediated immunomodulation. We aimed to determine the effects of HBM on proliferation of LR 17938 in vitro and its associated proteins and metabolites in culture, in order to provide mechanistic insights into the health benefits of LR 17938. LR 17938 was cultured anaerobically in MRS bacterial culture media, HBM (from 6 mothers), and 2 types of cow-milk formula. The colony-forming unit (CFU) was calculated to evaluate LR 17938 growth. Sixteen-hour-fermented supernatants were used for metabolomics, and bacterial lysates were used for proteomics analysis. We found that growth of LR 17938 was 10 times better in HBM than in formula. We detected 261/452 metabolites upregulated when LR 17938 cultured in HBM compared to in formula, mainly participating in the glyoxylate cycle (succinate), urea cycle (citrulline), methionine methylation (N-acetylcysteine), and polyamine synthesis (spermidine). The significantly up-regulated enzymes were also involved in the formation of acetyl-CoA in the glyoxylate cycle and the antioxidant N-acetylcysteine. In conclusion, HBM enhances the growth of LR 17938 compared to formula and promotes LR 17938-associated metabolites that relate to energy and antioxidant status, which may be linked to the physiological effects of L. reuteri.

[1]  A. Ouwehand,et al.  Selective Utilization of Human Milk Oligosaccharides 2'-FL and 3-FL by Probiotic Bacteria Resulting in Different Metabolite Production by These Bacteria (P20-012-19). , 2019, Current developments in nutrition.

[2]  R. Tofalo,et al.  Polyamines and Gut Microbiota , 2019, Front. Nutr..

[3]  K. Kang,et al.  N-acetylcysteine modulates lipopolysaccharide-induced intestinal dysfunction , 2019, Scientific Reports.

[4]  D. Tran,et al.  888 - Human Breast Milk Promotes Microbial Proliferation and Improves the Immunomodulatory Properties of Lactobacillus Reuteri DSM 17938 , 2018 .

[5]  M. Rafieian-kopaei,et al.  Probiotics are a good choice in remission of inflammatory bowel diseases: A meta analysis and systematic review , 2018, Journal of cellular physiology.

[6]  M. Cabana,et al.  Lactobacillus reuteri to Treat Infant Colic: A Meta-analysis , 2018, Pediatrics.

[7]  Z. Ruan,et al.  Effect of probiotic Lactobacillus on lipid profile: A systematic review and meta-analysis of randomized, controlled trials , 2017, PloS one.

[8]  R. Scandurra,et al.  Chondroprotective activity of N-acetyl phenylalanine glucosamine derivative on knee joint structure and inflammation in a murine model of osteoarthritis. , 2017, Osteoarthritis and cartilage.

[9]  P. Déchelotte,et al.  Glutamine and the regulation of intestinal permeability: from bench to bedside , 2017, Current opinion in clinical nutrition and metabolic care.

[10]  J. Sirard,et al.  Local Treatment with Lactate Prevents Intestinal Inflammation in the TNBS-Induced Colitis Model , 2016, Front. Immunol..

[11]  Karen C. Goehring,et al.  Similar to Those Who Are Breastfed, Infants Fed a Formula Containing 2'-Fucosyllactose Have Lower Inflammatory Cytokines in a Randomized Controlled Trial. , 2016, The Journal of nutrition.

[12]  Li Liu,et al.  Human milk oligosaccharides: The role in the fine-tuning of innate immune responses. , 2016, Carbohydrate research.

[13]  H. Schroten,et al.  Structural Basis for Norovirus Inhibition by Human Milk Oligosaccharides , 2016, Journal of Virology.

[14]  B. Jiang,et al.  Modular pathway rewiring of Saccharomyces cerevisiae enables high-level production of L-ornithine , 2015, Nature Communications.

[15]  P. Moayyedi,et al.  Efficacy of Prebiotics, Probiotics, and Synbiotics in Irritable Bowel Syndrome and Chronic Idiopathic Constipation: Systematic Review and Meta-analysis , 2014, The American Journal of Gastroenterology.

[16]  D. Tran,et al.  Lactobacillus reuteri DSM 17938 differentially modulates effector memory T cells and Foxp3+ regulatory T cells in a mouse model of necrotizing enterocolitis. , 2014, American journal of physiology. Gastrointestinal and liver physiology.

[17]  M. Karlsson Evaluation of Lactobacillus reuteri DSM17938 as starter in cheese production , 2013 .

[18]  V. Palda,et al.  Probiotics for the prevention of antibiotic-associated diarrhea and Clostridium difficile infection among hospitalized patients: systematic review and meta-analysis , 2013, Open medicine : a peer-reviewed, independent, open-access journal.

[19]  D. Tran,et al.  Lactobacillus reuteri DSM 17938 Changes the Frequency of Foxp3+ Regulatory T Cells in the Intestine and Mesenteric Lymph Node in Experimental Necrotizing Enterocolitis , 2013, PloS one.

[20]  J. C. Chapman,et al.  Arginine and citrulline protect intestinal cell monolayer tight junctions from hypoxia-induced injury in piglets , 2012, Pediatric Research.

[21]  J. M. Rhoads,et al.  Lactobacillus reuteri strains reduce incidence and severity of experimental necrotizing enterocolitis via modulation of TLR4 and NF-κB signaling in the intestine. , 2012, American journal of physiology. Gastrointestinal and liver physiology.

[22]  Pooneh Salari,et al.  A meta-analysis and systematic review on the effect of probiotics in acute diarrhea. , 2012, Inflammation & allergy drug targets.

[23]  Elizabeth T. Chang,et al.  Polyamines and Gut Mucosal Homeostasis. , 2012, Journal of gastrointestinal & digestive system.

[24]  R. Scandurra,et al.  A peptidyl-glucosamine derivative affects IKKα kinase activity in human chondrocytes , 2010, Arthritis research & therapy.

[25]  S. Roos,et al.  Removal of Antibiotic Resistance Gene-Carrying Plasmids from Lactobacillus reuteri ATCC 55730 and Characterization of the Resulting Daughter Strain, L. reuteri DSM 17938 , 2008, Applied and Environmental Microbiology.

[26]  E. Claud,et al.  Bacterial Colonization, Probiotics, and Necrotizing Enterocolitis , 2008, Journal of clinical gastroenterology.

[27]  D. Bassler,et al.  Probiotics for prevention of necrotizing enterocolitis in preterm infants (Review) , 2014 .

[28]  G. Kociubinski,et al.  Maternal breast‐milk and intestinal bifidobacteria guide the compositional development of the Bifidobacterium microbiota in infants at risk of allergic disease , 2007, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[29]  S. Salminen,et al.  Breast Milk: A Source of Bifidobacteria for Infant Gut Development and Maturation? , 2007, Neonatology.

[30]  K. Kashiwagi,et al.  Excretion of Putrescine and Spermidine by the Protein Encoded by YKL174c (TPO5) in Saccharomyces cerevisiae* , 2005, Journal of Biological Chemistry.

[31]  J. Galanko,et al.  Serum citrulline levels correlate with enteral tolerance and bowel length in infants with short bowel syndrome. , 2005, The Journal of pediatrics.

[32]  S. Salminen,et al.  Effects of Polyunsaturated Fatty Acids in Growth Medium on Lipid Composition and on Physicochemical Surface Properties of Lactobacilli , 2004, Applied and Environmental Microbiology.

[33]  R. Polin,et al.  Treatment and prevention of necrotizing enterocolitis , 2003, Seminars in Neonatology.

[34]  R. McCuskey,et al.  Epidermal growth factor reduces the development of necrotizing enterocolitis in a neonatal rat model. , 2002, American journal of physiology. Gastrointestinal and liver physiology.