Publications
Gut physiology and environment explain variations in human gut microbiome composition and metabolism
Procházková et al. 2024
The human gut microbiome is highly personal. However, the contribution of gut physiology and environment to variations in the gut microbiome remains understudied. Here we performed an observational trial using multi-omics to profile microbiome composition and metabolism in 61 healthy adults for 9 consecutive days. We assessed day-to-day changes in gut environmental factors and measured whole-gut and segmental intestinal transit time and pH using a wireless motility capsule in a subset of 50 individuals.
DOI: https://doi.org/10.1038/s41564-024-01856-x 27 November 2024
Regulation of microbial gene expression: the key to understanding our gut microbiome
Sinha et al. 2024
During the past two decades, gut microbiome studies have established the significant impact of the gut microbiota and its metabolites on host health. However, the molecular mechanisms governing the production of microbial metabolites in the gut environment remain insufficiently investigated and thus are poorly understood. Here, we propose that an enhanced understanding of gut microbial gene regulation, which is responsive to dietary components and gut environmental conditions, is needed in the research field and essential for our ability to effectively promote host health and prevent diseases through interventions targeting the gut microbiome.
DOI: https://doi.org/10.1016/j.tim.2024.07.005 01 August 2024
Towards nutrition with precision: unlocking biomarkers as dietary assessment tools
Cuparencu et al. 2024
Precision nutrition requires precise tools to monitor dietary habits. Yet current dietary assessment instruments are subjective, limiting our understanding of the causal relationships between diet and health. Biomarkers of food intake (BFIs) hold promise to increase the objectivity and accuracy of dietary assessment, enabling adjustment for compliance and misreporting. Here, we update current concepts and provide a comprehensive overview of BFIs measured in urine and blood.
DOI: https://doi.org/10.1038/s42255-024-01067-y 02 July 2024
Dietary fibre directs microbial tryptophan metabolism via metabolic interactions in the gut microbiota
Sinha et al. 2024
Tryptophan is catabolized by gut microorganisms resulting in a wide range of metabolites implicated in both beneficial and adverse host effects. How gut microbial tryptophan metabolism is directed towards indole, associated with chronic kidney disease, or towards protective indolelactic acid (ILA) and indolepropionic acid (IPA) is unclear. Here we used in vitro culturing and animal experiments to assess gut microbial competition for tryptophan and the resulting metabolites in a controlled three-species defined community and in complex undefined human faecal communities. 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.
DOI: https://doi.org/10.1038/s41564-024-01737-3 25 June 2024
D-Amino acids from foods and gut microbiota and their effects in health and disease
Roskjær et al. 2024
The D-enantiomers of L-amino acids are non-proteinogenic but widely present in foods. This is due to spontaneous racemization or processing, such as heating or alkali treatment, leading to substantial dietary exposure. Additional exposure to D-amino acids (D-AAs) comes from the human microbiota; D-AAs are present in bacterial surface proteoglycans, essential for bacterial competition and growth. Humans and other mammals have a complex set of genes for D-AA transport and degradation, and capacity to synthesize several D-AAs. Free D-AAs are present at low levels in human tissues and body fluids, yet they are apparently of considerable physiological and pathological importance. Amino acid transport regulates their presence and favors specific D-AAs, e.g. D-serine, D-aspartate, D-cysteine, and D-glutamate, over many others.
DOI: https://doi.org/10.1080/87559129.2024.2347472 30 May 2024
microbeMASST: a taxonomically informed mass spectrometry search tool for microbial metabolomics data
Zuffa et al. 2024
microbeMASST, a taxonomically informed mass spectrometry (MS) search tool, tackles limited microbial metabolite annotation in untargeted metabolomics experiments. Leveraging a curated database of >60,000 microbial monocultures, users can search known and unknown MS/MS spectra and link them to their respective microbial producers via MS/MS fragmentation patterns. Identification of microbe-derived metabolites and relative producers without a priori knowledge will vastly enhance the understanding of microorganisms’ role in ecology and human health.
DOI: https://doi.org/10.1038/s41564-023-01575-9 05 February 2024
Human milk oligosaccharides modify the strength of priority effects in the Bifidobacterium community assembly during infancy
Laursen and Roager, 2023
Despite the significant role of the gut microbiota in infant health and development, little is known about the ecological processes determining gut microbial community assembly. According to ecology theory, the timing and order of arrival of microbial species into an ecosystem affect microbial community assembly, a phenomenon termed priority effects. Bifidobacterium species are recognized as highly abundant early colonizers of the infant’s gut, partly due to their ability to selectively utilize human milk oligosaccharides (HMOs) from breast milk. However, the role of priority effects in Bifidobacterium community assembly remains unclear. Here, we investigated the Bifidobacterium community assembly in the gut of 25 breastfed Danish infants longitudinally sampled throughout the first 6 months of life. Our results showed that the breastfed infants were often initially, but temporarily, dominated by suboptimal HMO-utilizing Bifidobacterium taxa, such as B. longum subsp. longum, before more efficient HMO-utilizers such as B. longum subsp. infantis, replaced the first colonizer as the dominant Bifidobacterium taxon.
DOI: https://doi.org/10.1038/s41396-023-01525-7 10 October 2023
Key bacterial taxa determine longitudinal dynamics of aromatic amino acid catabolism in infants’ gut
Laursen et al. 2023
The development of the gut microbiota in early life is linked to metabolic, neuronal, and immunological development. Recent studies have shown that bacterial production of short-chain fatty acids (SCFAs) and aromatic amino acid (AAA) catabolites in the gut can mediate host–microbe interactions. However, the dynamics of these microbiota-derived metabolites and the key bacterial taxa producing AAA catabolites during infancy are largely unknown. Here, we investigated the longitudinal dynamics of the microbiota and microbiota-derived SCFAs and AAA catabolites in more than 200 fecal samples from 25 healthy breast- or mixed-fed Danish infants during the first 6 months of life. We found that the gut microbiota composition and metabolism were highly individual but showed significant development over time.
DOI: https://doi.org/10.1080/19490976.2023.2221426 25 June 2023
Effects of a wholegrain-rich diet on markers of colonic fermentation and bowel function and their associations with the gut microbiome: a randomised controlled cross-over trial
Procházková et al. 2023
Diets rich in whole grains are associated with health benefits. Yet, it remains unclear whether the benefits are mediated by changes in gut function and fermentation. We explored the effects of whole-grain vs. refined-grain diets on markers of colonic fermentation and bowel function, as well as their associations with the gut microbiome.
DOI: https://doi.org/10.3389/fnut.2023.1187165 01 June 2023
Stool energy density is positively correlated to intestinal transit time and related to microbial enterotypes
Boekhorst et al. 2022
It has been hypothesised that the gut microbiota causally affects obesity via its capacity to extract energy from the diet. Yet, evidence elucidating the role of particular human microbial community structures and determinants of microbiota-dependent energy harvest is lacking. Here, we investigated whether energy extraction from the diet in 85 overweight adults, estimated by dry stool energy density, was associated with intestinal transit time and variations in microbial community diversity and overall structure stratified as enterotypes. We hypothesised that a slower intestinal transit would allow for more energy extraction. However, opposite of what we expected, the stool energy density was positively associated with intestinal transit time. Stratifications into enterotypes showed that individuals with a Bacteroides enterotype (B-type) had significantly lower stool energy density, shorter intestinal transit times, and lower alpha-diversity compared to individuals with a Ruminococcaceae enterotype (R-type).
DOI: https://doi.org/10.1186/s40168-022-01418-5 12 December 2022
Advancing human gut microbiota research by considering gut transit time
Procházková et al. 2022
Accumulating evidence indicates that gut transit time is a key factor in shaping the gut microbiota composition and activity, which are linked to human health. Both population-wide and small-scale studies have identified transit time as a top covariate contributing to the large interindividual variation in the faecal microbiota composition. Despite this, transit time is still rarely being considered in the field of the human gut microbiome. Here, we review the latest research describing how and why whole gut and segmental transit times vary substantially between and within individuals, and how variations in gut transit time impact the gut microbiota composition, diversity and metabolism. Furthermore, we discuss the mechanisms by which the gut microbiota may causally affect gut motility.
DOI: 10.1136/gutjnl-2022-328166 10 September 2022
Prevotella abundance and salivary amylase gene copy number predict fat loss in response to wholegrain diets
Christensen et al. 2022
Salivary amylase (AMY1) gene copy number (CN) and Prevotella abundance in the gut are involved in carbohydrate digestion in the upper and lower gastrointestinal tract, respectively; and have been suggested as prognostic biomarkers for weight loss among overweight individuals consuming diets rich in fiber and wholegrains.
In both studies, individuals with low AMY1 CN exhibited a positive correlation between baseline Prevotella abundance and fat loss after consuming the wholegrain diet (r > 0.5, P < 0.05), but no correlation among participants with high AMY1 CN (P ≥ 0.6). Following consumption of the refined wheat control diets, there were no associations between baseline Prevotella abundance and changes in body fat in any of the AMY1 groups.
DOI: https://doi.org/10.3389/fnut.2022.947349 22 August 2022
Safety and efficacy of liraglutide versus colesevelam for the treatment of bile acid diarrhoea: a randomised, double-blind, active-comparator, non-inferiority clinical trial
Kårhus et al. 2022
Bile acid diarrhoea is an underdiagnosed disease estimated to affect 1–2% of the general population. Case reports indicate that the glucagon-like peptide 1 receptor agonist liraglutide might be an effective treatment for bile acid diarrhoea. We aimed to investigate the safety and efficacy of liraglutide for the treatment of bile acid diarrhoea.
DOI: https://doi.org/10.1016/S2468-1253(22)00198-4 20 July 2022
Personal diet-microbiota interactions and weight loss
Roager et al. 2022
The aim of this review is to provide an overview of how person-specific interactions between diet and the gut microbiota could play a role in affecting diet-induced weight loss responses. The highly person-specific gut microbiota, which is shaped by our diet, secretes digestive enzymes and molecules that affect digestion in the colon. Therefore, weight loss responses could in part depend on personal colonic fermentation responses, which affect energy extraction of food and production of microbial metabolites, such as short-chain fatty acids (SCFAs), which exert various effects on host metabolism. Colonic fermentation is the net result of the complex interplay between availability of dietary substrates, the functional capacity of the gut microbiome and environmental (abiotic) factors in the gut such as pH and transit time.
DOI: https://doi.org/10.1017/S0029665122000805 17 February 2022
The Gut Microbiome and Abiotic Factors as Potential Determinants of Postprandial Glucose Responses: A Single-Arm Meal Study
Nestel et al. 2021
The gut microbiome has combined with other person-specific information, such as blood parameters, dietary habits, anthropometrics, and physical activity been found to predict personalized postprandial glucose responses (PPGRs) to various foods. Yet, the contributions of specific microbiome taxa, measures of fermentation, and abiotic factors in the colon to glycemic control remain elusive. We tested whether PPGRs 60min after a standardized breakfast was associated with gut microbial a-diversity (primary outcome) and explored whether postprandial responses of glucose and insulin were associated with specific microbiome taxa, colonic fermentation as reflected by fecal short-chain fatty acids (SCFAs), and breath hydrogen and methane exhalation, as well as abiotic factors including fecal pH, fecal water content, fecal energy density, intestinal transit time (ITT), and stool consistency.
DOI https://doi.org/10.3389/fnut.2020.594850 14 January 2021
Settlers of our inner surface – factors shaping the gut microbiota from birth to toddlerhood
Laursen et al. 2021
During the first 3 years of life, the microbial ecosystem within the human gut undergoes a process that is unlike what happens in this ecosystem at any other time of our life. This period in time is considered a highly important developmental window, where the gut microbiota is much less resilient and much more responsive to external and environmental factors than seen in the adult gut. While advanced bioinformatics and clinical correlation studies have received extensive focus within studies of the human microbiome, basic microbial growth physiology has attracted much less attention, although it plays a pivotal role to understand the developing gut microbiota during early life. In this review, we will thus take a microbial ecology perspective on the analysis of factors that influence the temporal development of the infant gut microbiota. Such factors include sources of microbes that seed the intestinal environment, physico-chemical (abiotic) conditions influencing microbial growth and the availability of nutrients needed by the intestinal microbes.
DOI: https://doi.org/10.1093/femsre/fuab001 11 January 2021
In vitro ecology: a discovery engine for microbiome therapies
Hernandez-Sanabria et al. 2020
To therapeutically modulate gut microbial ecosystems, a better understanding of gut ecology is key. High-throughput in vitro ecology provides a tool with the necessary power to address these needs and interpersonal treatment response variation.
DOI https://doi.org/10.1038/s41575-020-00364-7 15 September 2020
The metabolic nature of individuality
Lars O. Dragsted, 2020
A diet-controlled study indicates that metabolic flexibility is an important driver of inter-individual difference in the response to dietary change, and a high flexibility score is a likely health asset.
DOI https://doi.org/10.1038/s43016-020-0104-z 17 June 2020