Biology subjects

Laursen, M. F.

Publications and source records attributed to Laursen, M. F..

4 recordsLinked to original sources

bioRxiv2025

Aromatic lactic acid production by Bifidobacterium longum subsp. infantis is determined by cell density, substrate availability and pH in vitro

Bifidobacterium longum subsp. infantis (B. infantis) is an important colonizer of the infant gut. This species is known to produce a variety of health beneficial metabolites, including aromatic lactic acids (ALAs), supporting early life immune development. However, the regulation of ALA production in B. infantis remains poorly understood. In this study, we investigated how environmental factors, such as substrate availability and pH affect B. infantis DSM20088 growth and ALA production in vitro. Bacterial batch cultivations supplemented with different amino acid concentrations revealed a linear relationship between indole-3-lactic acid (ILA), 4-hydroxyphenyllactic acid (OH-PLA), and phenyllactic acid (PLA) production and exogenous concentrations of tryptophan, tyrosine and phenylalanine, respectively. Furthermore, chemostat cultivations at physiological relevant pH levels (4.5, 5.5 and 6.5) showed that an acidic pH slowed growth and shifted ALA production by B. infantis. Overall, ALA concentrations correlated strongly with bacterial abundance across and within pH levels, showing that cell density is a major determinant of ALA production. After considering the growth limiting effects of lower environmental pH, it had limited impact on the total production of ALAs, but the relative production of PLA was stepwise enhanced at more acidic pH at the expense of ILA, independent of cell density. In conclusion, this study shows that cell density, substrate availability and environmental pH determine aromatic lactic acid production by B. infantis. ImportanceBifidobacterium longum subsp. infantis is an abundant bacterial species in the infant gut microbiota where it supports immune development e.g. though the production of aromatic lactic acids. In this study we cultured Bifidobacterium longum subsp. infantis at different concentrations of aromatic amino acids and pH levels to investigate the effect of these environmental factors on aromatic lactic acid production. We show that there is a linear relationship between aromatic lactic acid production and the exogenous aromatic amino acid concentration, that the production strongly follows cell density, and that pH regulates the preference towards producing different aromatic lactic acids. This knowledge may help inform strategies to enhance or direct beneficial ALA production in the infant gut.

microbiology↗

bioRxiv2024

Gut environmental factors explain variations in the gut microbiome composition and metabolism within and between healthy adults

The human gut microbiome is highly personal. However, the contribution of the gut environment to variations in the gut microbiome remains elusive. Here, we profiled the gut microbiome composition and metabolism over 9 consecutive days in 61 healthy adults and assessed gut environmental factors including segmental transit time and pH using a wireless motility capsule. Day-to-day fluctuations in gut environmental factors as well as segmental transit time and pH varied substantially between individuals. The gut environment explained more variations in gut microbiome and urine metabolome than dietary macronutrients or personal characteristics. Finally, we identified coffee-derived metabolites to be negatively correlated with small intestinal transit time and several microbial metabolites to be associated with colonic transit time including urinary proteolytic markers, faecal short-chain fatty acids, and breath methane. Our work suggests that the gut environment is key for understanding the individuality of the human gut microbiome composition and metabolism.

microbiology↗

bioRxiv2023

Substrate availability and dietary fibre regulate metabolism of tryptophan by human gut microbes

Tryptophan is catabolized by gut microbes, resulting in a wide range of metabolites implicated in both beneficial and adverse host effects. However, it remains elusive how the gut microbial tryptophan metabolism is governed either towards indole, associated with adverse effects in chronic kidney disease, or towards indolelactic acid (ILA) and indolepropionic acid (IPA), associated with protective effects in type 2 diabetes and inflammatory bowel disease. Here, we used human fecal cultures in combination with a controlled three-species model to test competition for tryptophan, and measured the resulting metabolites both in vitro and in gnotobiotic mice colonized with the three species. We revealed that the generation of specific tryptophan-derived metabolites was not predominantly determined by the abundance of tryptophan metabolizing bacteria, but rather by substrate-dependent regulation of specific metabolic pathways. In vitro and in vivo, indole-producing Escherichia coli and ILA- and IPA-producing Clostridium sporogenes competed for tryptophan. Importantly, the fibre degrading Bacteroides thetaiotaomicron affected this competition by cross-feeding monosaccharides to E. coli, which inhibited indole production through catabolite repression, and thereby made more tryptophan available to C. sporogenes, increasing ILA and IPA production. We thus present the first mechanistic explanation for why consumption of fermentable fibres suppress indole production but promote the generation of other tryptophan metabolites associated with health benefits. We conclude that the availability of tryptophan and dietary fibre regulates gut microbiome tryptophan metabolism pathways, and consequently influences the balance between the different tryptophan catabolites generated. This balance has implications for host-microbial cross-talk affecting human health.

microbiology↗

bioRxiv2020

Breastmilk-promoted bifidobacteria produce aromatic lactic acids in the infant gut

Breastfeeding 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.

microbiology↗