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Impact of probiotic Limosilactobacillus reuteri DSM 17938 on amino acid metabolism in the healthy newborn mouse.

ABSTRACT: We studied the effect of feeding a single probiotic Limosilactobacillus reuteri DSM 17938 (LR 17938) on the luminal and plasma levels of amino acids and their derivatives in the suckling newborn mouse, using gas chromatography and high-performance liquid chromatography. We found that LR 17938 increased the relative abundance of many amino acids and their derivatives in stool, while it simultaneously significantly reduced the plasma levels of three amino acids (serine, citrulline, and taurine). Many peptides and dipeptides were increased in stool and plasma, notably gamma-glutamyl derivatives of amino acids, following ingestion of the LR 17938. Gamma-glutamyl transformation of amino acids facilitates their absorption. LR 17938 significantly upregulated N-acetylated amino acids, the levels of which could be useful biomarkers in plasma and warrant further investigation. Specific fecal microbiota were associated with higher levels of fecal amino acids and their derivatives. Changes in luminal and circulating levels of amino acid derivatives, polyamines, and tryptophan metabolites may be mechanistically related to probiotic efficacy.

SUBMITTER: Liu Y

PROVIDER: S-EPMC9643610 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Impact of probiotic Limosilactobacillus reuteri DSM 17938 on amino acid metabolism in the healthy newborn mouse.

Liu Yuying Y Tian Xiangjun X Daniel Rhea C RC Okeugo Beanna B Armbrister Shabba A SA Luo Meng M Taylor Christopher M CM Wu Guoyao G Rhoads J Marc JM

Amino acids 20220510 10

We studied the effect of feeding a single probiotic Limosilactobacillus reuteri DSM 17938 (LR 17938) on the luminal and plasma levels of amino acids and their derivatives in the suckling newborn mouse, using gas chromatography and high-performance liquid chromatography. We found that LR 17938 increased the relative abundance of many amino acids and their derivatives in stool, while it simultaneously significantly reduced the plasma levels of three amino acids (serine, citrulline, and taurine). M ...[more]

PMID: 35536363

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Project description:Improved efficacy of probiotics can be achieved by using different strategies, including the optimization of production parameters. The impact of fermentation parameters on bacterial physiology is a frequently investigated topic, but what happens during the formulation, i.e., the step where the lyoprotectants are added prior to freeze-drying, is less studied. In addition to this, the focus of process optimization has often been yield and stability, while effects on bioactivity have received less attention. In this work, we investigated different metabolic activities of the probiotic strain Limosilactobacillus reuteri DSM 17938 during formulation with the freeze-drying protectant sucrose. We discovered that the strain consumed large quantities of the added sucrose and produced an exopolysaccharide (EPS). Using NMR, we discovered that the produced EPS was a glucan with α-1,4 and α-1,6 glycosidic bonds, but also that other metabolites were produced. The conversion of the lyoprotectant is hereafter designated lyoconversion. By also analyzing the samples with GCMS, additional potential bioactive compounds could be detected. Among these were tryptamine, a ligand for the aryl hydrocarbon receptor, and glycerol, a precursor for the antimicrobial compound reuterin (3-hydroxypropionaldehyde). To exemplify the bioactivity potential of lyoconversion, lyoconverted samples as well as purified EPS were tested in a model for immunomodulation. Both lyoconverted samples and purified EPS induced higher expression levels of IL-10 (2 times) and IL-6 (4-6 times) in peripheral blood mononuclear cells than non-converted control samples. We further found that the initial cultivation of DSM 17938 with sucrose as a sugar substrate, instead of glucose, improved the ability to convert sucrose in the lyoprotectant into EPS and other metabolites. Lyoconversion did not affect the viability of the bacteria but was detrimental to freeze-drying survival, an issue that needs to be addressed in the future. In conclusion, we show that the metabolic activities of the bacteria during the formulation step can be used as a tool to alter the activity of the bacteria and thereby potentially improve probiotic efficacy.

Project description:Studies have shown that probiotics can decrease the symptoms of respiratory tract infections as well as increase antibody responses following certain vaccinations. We examined the effect of probiotic supplementation on anti-SARS-CoV-2 specific antibody responses upon SARS-CoV-2 infection as well as after COVID-19 vaccination. In this randomized, triple-blinded, placebo-controlled intervention study with a parallel design, 159 healthy adults without prior SARS-CoV-2 infection or COVID-19 vaccination and any known risk factors for severe COVID-19 were randomly allocated into two study arms. The active treatment arm consumed a probiotic product containing a minimum of 1 × 108 colony-forming units of Limosilactobacillus reuteri DSM 17938 + 10 μg vitamin D3 twice daily for 6 months. The placebo arm consumed identical tablets containing only 10 μg vitamin D3. Anti-SARS-CoV-2 specific antibodies and virus neutralizing antibody titers were analyzed from blood samples collected at baseline, after 3 months, and after 6 months. Differences in serum antibody titers between the two study arms were tested with independent t-test using log-transformed values. In the intention-to-treat (ITT) analysis, SARS-CoV-2 infected individuals in the active treatment arm (n = 6) tended to have higher serum anti-spike IgG (609 [168-1480] BAU/ml vs 111 [36.1-1210] BAU/ml, p = 0.080) and anti-receptor binding domain (RBD) IgG (928 [212-3449] BAU/ml vs (83.7 [22.8-2094] BAU/ml, p = 0.066) levels than individuals in the placebo arm (n = 6). Considering individuals who were fully vaccinated with mRNA-based COVID-19 vaccines, the active treatment arm (n = 10) exhibited significantly higher serum levels of anti-RBD IgA (135 [32.9-976] BAU/ml vs 61.3 [26.7-97.1] BAU/ml, p = 0.036) than the placebo arm (n = 7) >28 days postvaccination. Supplementation with specific probiotics might improve the long-term efficacy of mRNA-based COVID-19 vaccines via enhanced IgA response.

Project description:Early administration of Lactobacillus reuteri DSM 17938 (LR) prevents necrotizing enterocolitis and inhibits regulatory T-cell (Treg)-deficiency-associated autoimmunity in mice. In humans, LR reduces crying time in breastfed infants with colic, modifies severity in infants with acute diarrheal illnesses, and improves pain in children with functional bowel disorders. In healthy breastfed newborns with evolving microbial colonization, it is unclear if early administration of LR can modulate gut microbiota and their metabolites in such a way as to promote homeostasis. We gavaged LR (107 colony-forming units/day, daily) to C57BL/6J mice at age of day 8 for 2 wk. Both male and female mice were investigated in these experiments. We found that feeding LR did not affect clinical phenotype or inflammatory biomarkers in plasma and stool, but LR increased the proportion of Foxp3+ regulatory T cells (Tregs) in the intestine. LR also increased bacterial diversity and the relative abundance of p_Firmicutes, f_Lachnospiraceae, f_Ruminococcaceae, and genera Clostridium and Candidatus arthromitus, while decreasing the relative abundance of p_Bacteriodetes, f_Bacteroidaceae, f_Verrucomicrobiaceae, and genera Bacteroides, Ruminococcus, Akkermansia, and Sutterella. Finally, LR exerted a major impact on the plasma metabolome, upregulating amino acid metabolites formed via the urea, tricarboxylic acid, and methionine cycles and increasing tryptophan metabolism. In conclusion, early oral administration of LR to healthy breastfed mice led to microbial and metabolic changes which could be beneficial to general health.NEW & NOTEWORTHY Oral administration of Lactobacillus reuteri DSM 17938 (LR) to healthy breastfed mice promotes intestinal immune tolerance and is linked to proliferation of beneficial gut microbiota. LR upregulates plasma metabolites that are involved in the urea cycle, the TCA cycle, methionine methylation, and the polyamine pathway. Herein, we show that LR given to newborn mice specifically increases levels of tryptophan metabolites and the purine nucleoside adenosine that are known to enhance tolerance to inflammatory stimuli.

Dataset Information

Impact of probiotic Limosilactobacillus reuteri DSM 17938 on amino acid metabolism in the healthy newborn mouse.

Publications

Impact of probiotic Limosilactobacillus reuteri DSM 17938 on amino acid metabolism in the healthy newborn mouse.

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