scholarly journals Bifidobacterium species associated with breastfeeding produce aromatic lactic acids in the infant gut

2021 ◽  
Author(s):  
Martin F. Laursen ◽  
Mikiyasu Sakanaka ◽  
Nicole von Burg ◽  
Urs Mörbe ◽  
Daniel Andersen ◽  
...  
Keyword(s):  
Amino Acids ◽  
Gut Microbiota ◽  
Immune Responses ◽  
Early Life ◽  
Bifidobacterium Longum ◽  
Aromatic Amino Acids ◽  
Dependent Manner ◽  
Microbial Metabolites ◽  
Phenyllactic Acid ◽  
Lactic Acids

AbstractBreastfeeding 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 (HCA3). 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.

scholarly journals Breastmilk-promoted bifidobacteria produce aromatic amino acids in the infant gut

2020 ◽  
Author(s):  
Martin F. Laursen ◽  
Mikiyasu Sakanaka ◽  
Nicole von Burg ◽  
Urs Mörbe ◽  
Daniel Andersen ◽  
...  
Keyword(s):  
Amino Acids ◽  
Lactate Dehydrogenase ◽  
Gut Microbiota ◽  
Immune Responses ◽  
Early Life ◽  
Aromatic Amino Acids ◽  
Dependent Manner ◽  
Microbial Metabolites ◽  
Stool Samples ◽  
Lactic Acids

ABSTRACTBreastfeeding profoundly shapes the infant gut microbiota, which is critical for early life immune development. However, few breastmilk-dependent microbial metabolites mediating host-microbiota interactions are currently known. We here demonstrate that breastmilk-promoted Bifidobacterium species convert aromatic amino acids (tryptophan, phenylalanine and tyrosine) into their respective aromatic lactic acids (indolelactate, phenyllactate and 4-hydroxyphenyllactate) via a previously unrecognised aromatic lactate dehydrogenase. By longitudinal profiling of the gut microbiota composition and metabolome of stool samples of infants obtained from birth until 6 months of age, we show that stool concentrations of aromatic lactic acids are determined by the abundance of human milk oligosaccharide degrading Bifidobacterium species containing the aromatic lactate dehydrogenase. We demonstrate that stool concentrations of Bifidobacterium-derived indolelactate, the most abundant aromatic lactic acid in vivo, are associated with the capacity of infant stool samples to activate the aryl hydrocarbon receptor (AhR), a receptor important for controlling intestinal homeostasis and immune responses. Finally, we show that indolelactate 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 (HCAR3). Our findings reveal that breastmilk-promoted Bifidobacterium produce aromatic lactic acids in the gut of infants and suggest that these microbial metabolites may impact immune function in early life.

scholarly journals Gut-Microbial Metabolites, Probiotics and Their Roles in Type 2 Diabetes

2021 ◽  
Vol 22 (23) ◽  
pp. 12846
Author(s):  
Lixiang Zhai ◽  
Jiayan Wu ◽  
Yan Y. Lam ◽  
Hiu Yee Kwan ◽  
Zhao-xiang Bian ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Amino Acids ◽  
Gut Microbiota ◽  
Aromatic Amino Acids ◽  
Microbial Metabolites ◽  
High Blood Glucose ◽  
Gaseous Products ◽  
Glucose Levels ◽  
Novel Therapeutic Strategies

Type 2 diabetes (T2D) is a worldwide prevalent metabolic disorder defined by high blood glucose levels due to insulin resistance (IR) and impaired insulin secretion. Understanding the mechanism of insulin action is of great importance to the continuing development of novel therapeutic strategies for the treatment of T2D. Disturbances of gut microbiota have been widely found in T2D patients and contribute to the development of IR. In the present article, we reviewed the pathological role of gut microbial metabolites including gaseous products, branched-chain amino acids (BCAAs) products, aromatic amino acids (AAAs) products, bile acids (BA) products, choline products and bacterial toxins in regulating insulin sensitivity in T2D. Following that, we summarized probiotics-based therapeutic strategy for the treatment of T2D with a focus on modulating gut microbiota in both animal and human studies. These results indicate that gut-microbial metabolites are involved in the pathogenesis of T2D and supplementation of probiotics could be beneficial to alleviate IR in T2D via modulation of gut microbiota.

scholarly journals The role of bacterial metabolites derived from aromatic amino acids in non-alcoholic fatty liver disease

2020 ◽  
Vol 48 (6) ◽  
pp. 375-386
Author(s):  
E. S. Shcherbakova ◽  
T. S. Sall ◽  
S. I. Sitkin ◽  
T. Ya. Vakhitov ◽  
E. V. Demyanova
Keyword(s):  
Amino Acids ◽  
Liver Disease ◽  
Gut Microbiota ◽  
Fatty Liver Disease ◽  
Liver Steatosis ◽  
Aromatic Amino Acids ◽  
Microbial Metabolites ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

The review deals with the role of aromatic amino acids and their microbial metabolites in the development and progression of non-alcoholic fatty liver disease (NAFLD). Pathological changes typical for NAFLD, as well as abnormal composition and/or functional activity of gut microbiota, results in abnormal aromatic amino acid metabolism. The authors discuss the potential of these amino acids and their bacterial metabolites to produce both negative and positive impact on the main steps of NAFLD pathophysiology, such as lipogenesis and inflammation, as well as on the liver functions through regulation of the intestinal barrier and microbiota-gut-liver axis signaling. The review gives detailed description of the mechanism of biological activity of tryptophan and its derivatives (indole, tryptamine, indole-lactic, indole-propyonic, indole-acetic acids, and indole-3-aldehyde) through the activation of aryl hydrocarbon receptor (AhR), preventing the development of liver steatosis. Bacteria-produced phenyl-alanine metabolites could promote liver steatosis (phenyl acetic and phenyl lactic acids) or, on the contrary, could reduce liver inflammation and increase insulin sensitivity (phenyl propionic acid). Tyramine, para-cumarate, 4-hydroxyphenylacetic acids, being by-products of bacterial catabolism of tyrosine, can prevent NAFLD, whereas para-cresol and phenol accelerate the progression of NAFLD by damaging the barrier properties of intestinal epithelium. Abnormalities in bacterial catabolism of tyrosine, leading to its excess, stimulate fatty acid synthesis and promote lipid infiltration of the liver. The authors emphasize a close interplay between bacterial metabolism of aromatic amino acids by gut microbiota and the functioning of the human body. They hypothesize that microbial metabolites of aromatic amino acids may represent not only therapeutic targets or non-invasive biomarkers, but also serve as bioactive agents for NAFLD treatment and prevention.

scholarly journals Early-Life Stress Modulates Gut Microbiota and Peripheral and Central Inflammation in a Sex-Dependent Manner

2021 ◽  
Vol 22 (4) ◽  
pp. 1899 ◽  
Author(s):  
Hae Jeong Park ◽  
Sang A. Kim ◽  
Won Sub Kang ◽  
Jong Woo Kim
Keyword(s):  
Gut Microbiota ◽  
Relative Abundance ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Female Rats ◽  
Rrna Gene ◽  
Dependent Manner ◽  
Male And Female Rats

Recent studies have reported that changes in gut microbiota composition could induce neuropsychiatric problems. In this study, we investigated alterations in gut microbiota induced by early-life stress (ELS) in rats subjected to maternal separation (MS; 6 h a day, postnatal days (PNDs) 1–21), along with changes in inflammatory cytokines and tryptophan-kynurenine (TRP-KYN) metabolism, and assessed the differences between sexes. High-throughput sequencing of the bacterial 16S rRNA gene showed that the relative abundance of the Bacteroides genus was increased and that of the Lachnospiraceae family was decreased in the feces of MS rats of both sexes (PND 56). By comparison, MS increased the relative abundance of the Streptococcus genus and decreased that of the Staphylococcus genus only in males, whereas the abundance of the Sporobacter genus was enhanced and that of the Mucispirillum genus was reduced by MS only in females. In addition, the levels of proinflammatory cytokines were increased in the colons (IFN-γ and IL-6) and sera (IL-1β) of the male MS rats, together with the elevation of the KYN/TRP ratio in the sera, but not in females. In the hippocampus, MS elevated the level of IL-1β and the KYN/TRP ratio in both male and female rats. These results indicate that MS induces peripheral and central inflammation and TRP-KYN metabolism in a sex-dependent manner, together with sex-specific changes in gut microbes.

scholarly journals IgA dysfunction induced by the early-lifetime disruption of gut microbiota aggravates diet–induced metabolic syndrome in mice

2021 ◽  
Author(s):  
Jielong Guo ◽  
Xue Han ◽  
Yilin You ◽  
Weidong Huang ◽  
Zhan Jicheng
Keyword(s):  
Metabolic Syndrome ◽  
Gut Microbiota ◽  
Early Life ◽  
Low Dose ◽  
Dependent Manner ◽  
Wild Type ◽  
Bacterial Composition ◽  
Germ Free ◽  
Iga Response ◽  
Intestinal Iga

Abstract BackgroundLow-dose antibiotic contamination in animal food is still a severe food safety problem worldwide. Penicillin is one of the main classes of antibiotics being detected in food. Previous studies have shown that transient exposure of low-dose penicillin (LDP) during early life resulted in metabolic syndrome (MetS) in mice. However, the underlying mechanism(s) and efficient approaches to counteracting this are largely unknown.MethodsWild-type (WT) or secretory IgA (SIgA)-deficient (Pigr-/-) C57BL/6 mice were exposed to LDP or not from several days before birth to 30 d of age. Five times of FMT or probiotics (a mixture of Lactobacillus bulgaricus and L. rhamnosus GG) treatments were applied to parts of these LDP-treated mice from 12 d to 28 d of life. Bacterial composition from different regions (mucosa and lumen) of the colon and ileum were analyzed through 16S rDNA sequencing. Intestinal IgA response was analyzed. Multiple parameters related to MetS were also determined. In addition, germ-free animals and in vitro tissue culture were also used to determine the correlations between LDP, gut microbiota (GM) and intestinal IgA response.ResultsLDP disturbed the intestinal bacterial composition, especially for ileal mucosa, the main inductive and effective sites of IgA response, in 30-d-old mice. The alteration of early GM resulted in a persistent inhibition of the intestinal IgA response, leading to a constant reduction of fecal and caecal SIgA levels throughout the 25-week experiment, which is early life-dependent, as transfer of LDP-GM to 30 d germ-free mice only resulted in a transient reduction in fecal SIgA. LDP-induced reduction in SIgA led to a decrease in IgA+ bacteria and a dysbiosis in the ileal mucosal samples of 25 week wild-type but not Pigr-/- mice. Moreover, LDP also resulted in increases in ileal bacterial encroachment and adipose inflammation, along with an enhancement of diet-induced MetS in an intestinal SIgA-dependent manner. Furthermore, several times of FMT or probiotic treatments during LDP treatment are efficient to fully (for FMT) or partially (for probiotics) counteract the LDP-effect on both GM and metabolism.ConclusionsEarly-life LDP-induced enhancement of diet-induced MetS is mediated by intestinal SIgA, which could be (partially) restored by FMT or probiotics treatment.

Gut Microbial Metabolites of Aromatic Amino Acids as Signals in Host–Microbe Interplay

2020 ◽  
Vol 31 (11) ◽  
pp. 818-834 ◽  
Author(s):  
Yali Liu ◽  
Yuanlong Hou ◽  
Guangji Wang ◽  
Xiao Zheng ◽  
Haiping Hao
Keyword(s):  
Amino Acids ◽  
Aromatic Amino Acids ◽  
Microbial Metabolites

scholarly journals Berberine alleviates type 2 diabetic symptoms by altering gut microbiota and reducing aromatic amino acids

2020 ◽  
Vol 131 ◽  
pp. 110669
Author(s):  
Ye Yao ◽  
Han Chen ◽  
Lijing Yan ◽  
Wenbo Wang ◽  
Dongsheng Wang
Keyword(s):  
Amino Acids ◽  
Gut Microbiota ◽  
Aromatic Amino Acids ◽  
Type 2 Diabetic

scholarly journals Supplementation with Combined Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 Across Development Reveals Sex Differences in Physiological and Behavioural Effects of Western Diet in Long–Evans Rats

2020 ◽  
Vol 8 (10) ◽  
pp. 1527
Author(s):  
Elizabeth M. Myles ◽  
M. Elizabeth O’Leary ◽  
Rylan Smith ◽  
Chad W. MacPherson ◽  
Alexandra Oprea ◽  
...  
Keyword(s):  
Sex Differences ◽  
Early Life ◽  
Bifidobacterium Longum ◽  
Western Diet ◽  
Lactobacillus Helveticus ◽  
Calorie Intake ◽  
Dependent Manner ◽  
Probiotic Treatment ◽  
Long Evans ◽  
Diet Exposure

The gut microbiome affects various physiological and psychological processes in animals and humans, and environmental influences profoundly impact its composition. Disorders such as anxiety, obesity, and inflammation have been associated with certain microbiome compositions, which may be modulated in early life. In 62 Long–Evans rats, we characterised the effects of lifelong Bifidobacterium longum R0175 and Lactobacillus helveticus R0052 administration—along with Western diet exposure—on later anxiety, metabolic consequences, and inflammation. We found that the probiotic formulation altered specific anxiety-like behaviours in adulthood. We further show distinct sex differences in metabolic measures. In females, probiotic treatment increased calorie intake and leptin levels without affecting body weight. In males, the probiotic seemed to mitigate the effects of Western diet on adult weight gain and calorie intake, without altering leptin levels. The greatest inflammatory response was seen in male, Western-diet-exposed, and probiotic-treated rats, which may be related to levels of specific steroid hormones in these groups. These results suggest that early-life probiotic supplementation and diet exposure can have particular implications on adult health in a sex-dependent manner, and highlight the need for further studies to examine the health outcomes of probiotic treatment in both sexes.

DEGRADATION OF AROMATIC AMINO ACIDS BY FUNGI: I. FATE OF L-PHENYLALANINE IN SCHIZOPHYLLUM COMMUNE

1967 ◽  
Vol 45 (11) ◽  
pp. 1659-1665 ◽  
Author(s):  
Keith Moore ◽  
G. H. N. Towers
Keyword(s):  
Amino Acids ◽  
Benzoic Acid ◽  
Protocatechuic Acid ◽  
Phenylacetic Acid ◽  
Schizophyllum Commune ◽  
Aromatic Amino Acids ◽  
Ring Cleavage ◽  
Hydroxybenzoic Acid ◽  
Phenyllactic Acid ◽  
Phenylalanine Metabolism

Growing cultures of Schizophyllum commune could produce 14CO2 from ring-labelled DL-phenylalanine-14C. Intermediates in the pathway of L-phenylalanine degradation prior to ring cleavage were shown to be cinnamic acid, benzoic acid, p-hydroxybenzoic acid, and protocatechuic acid. Phenylacetic acid and L(−)-β-phenyllactic acid were also identified as products of phenylalanine metabolism.

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