Biology subjects

Looijesteijn, E.

Publications and source records attributed to Looijesteijn, E..

4 recordsLinked to original sources

bioRxiv2026

Feeding-mode-defined microbial communities modulate prebiotic responses and alters colonic motility in early life

Prebiotic supplementation a well-established impact on early-life gut microbiota, yet how substrate type and baseline community structure interact to shape microbial and metabolic responses remains incompletely understood. Using donor-derived infant faecal fermentations, a defined synthetic microbial community (SynCom), and multi-layered metabolomics, we demonstrate that prebiotic responses are strongly dependent on feeding-mode and mediated by species-specific metabolic interactions. While both human milk oligosaccharides (HMOs) and galacto-oligosaccharides (GOS) robustly promoted bifidobacterial expansion, modulation of Bacteroides/Phocaeicola species varied according to feeding background and substrate identity with 2'-fucosyllactose (2'FL) selectively alleviating growth inhibition in breast milk-derived communities. Mechanistic dissection using SynCom revealed extensive cross-feeding networks and substrate-dependent interaction rewiring, identifying Phocaeicola vulgatus as a context-dependent ecological hub that disproportionately shaped succinate and propionate production and altered Escherichia coli metabolic activity without affecting its abundance. Competitive outcomes were determined not only by environmental acidification, but also by the chemical identity of fermentation products, with lactate exerting species-specific inhibitory effects independent of bulk pH changes. Using an in-house ex vivo IntestiFlow gut organ platform, we further show that metabolites produced by the defined community induced a strong but reversible suppression of colonic peristaltic activity, an effect not recapitulated by SCFAs alone. Biogenic amine metabolites, including phenethylamine, partially reproduced key aspects of this response, suggesting a role for specific microbial fermentation products in modulating intestinal motility. Together, these findings demonstrate that early-life prebiotic responses extend beyond uniform bifidogenic expansion and instead emerge from interaction-driven metabolic specialization within feeding-mode-specific community contexts, with direct functional consequences for infant intestinal physiology.

microbiology↗

bioRxiv2024

Simulations of the infant gut microbiota suggest that complex ecological interactions regulate effects of human milk oligosaccharides on microbial mucin consumption

Intestinal mucin acts as a barrier protecting the infant gut wall against diseases such as colitis and rotavirus. In vitro experiments have shown that the gut microbiota of breastfed infants consumes less mucin than the microbiota of non-breastfed infants, but the mechanisms are incompletely understood. The main difference between human milk and most infant formulas is the presence of human milk oligosaccharides (HMOs) in human milk. We hypothesize that HMOs protect mucin by stimulating non-mucin consuming bacteria. To understand the un-derlying mechanisms we developed a computational model that describes the metabolism and ecology of the infant gut microbiota. Model simulations suggest that extracellular digestion of the HMO 2-fucosyllactose by the mucin-consumer Bifidobacterium bifidum may make this species vulnerable to competitors. The digestion products of HMOs become public goods that can be consumed by competing species such as Bacteroides vulgatus instead.Bifidobacterium longum, which does not consume mucin or produce public goods, can then become dominant, despite growing less efficiently on HMOs in monocultures than B. bifidum. In conclusion, our model simulations suggest that, through complex ecological interactions, HMOs may help lower mucin consumption by stimulating the non-mucin consumer B. longum at the expense of the mucin consumer B. bifidum.

systems biology↗

bioRxiv2023

2'-Fucosyllactose helps butyrate producers outgrow competitors in the infant gut

A reduced capacity for butyrate production by the early infant gut microbiota is associated with negative health effects, such as inflammation and the development of allergies. Here we develop new hypotheses on the effect of the prebiotic galacto-oligosaccharides (GOS) or 2-fucosyllactose (2-FL) on butyrate production by the infant gut microbiota using a multiscale, spatiotemporal mathematical model of the infant gut. The model simulates a community of cross-feeding gut bacteria at metabolic detail. It represents the gut microbiome as a grid of bacterial populations that exchange intermediary metabolites, using 20 different subspecies-specific metabolic networks taken from the AGORA database. The simulations predict that both GOS and 2-FL promote the growth of Bifidobacterium, whereas butyrate producing bacteria are only consistently abundant in the presence of propane-1,2-diol, a product of 2-FL metabolism. The results suggest that in absence of prebiotics or in presence of only GOS, bacterial species, including Cutibacterium acnes and Bacteroides vulgatus, outcompete butyrate producers by feeding on intermediary metabolites. In presence of 2-FL, however, production of propane-1,2-diol specifically supports butyrate producers.

systems biology↗

bioRxiv2021

A multiscale spatiotemporal model explains succession in the early infant gut microbiota as a switch from aerobic to anaerobic metabolism

The human intestinal microbiota starts to form immediately after birth, and is important for the health of the host. During the first days facultatively anaerobic bacterial species generally dominate, such as Enterobacteriaceae. These are succeeded by strictly anaerobic species, particularly Bifidobacterium species. An early transition to Bifidobacterium species is associated with health benefits: for example, Bifidobacterium species repress growth of pathogenic competitors and modulate the immune response. Succession to Bifidobacterium is thought to be due to consumption of intracolonic oxygen present in newborns by facultative anaerobes, including Enterobacteriaceae. To study if oxygen depletion suffices for the transition to Bifidobacterium species, here we introduce a multiscale mathematical model that considers metabolism, spatial bacterial population dynamics and cross-feeding. Using publicly available metabolic network data from the AGORA collection, the model simulates ab initio the competition of strictly and facultatively anaerobic species in a gut-like environment under the influence of lactose and oxygen. The model predicts that individual differences in intracolonic oxygen in newborn infants can explain the observed individual variation in succession to anaerobic species, in particular Bifidobacterium species. Bifidobacterium species become dominant in the model by using the bifid shunt, which allows Bifidobacterium to switch to sub-optimal yield metabolism with fast growth at high lactose concentrations as predicted here using flux-balance analysis. The computational model thus allows us to test the internal plausibility of hypotheses for bacterial colonization and succession in the infant colon. IMPORTANCEThe composition of the infant microbiota has a great impact on infant health, but its controlling factors are still incompletely understood. The frequently dominant anaerobic Bifidobacterium species benefit health, e.g., because they can keep harmful competitors under control and modulate the intestinal immune response. Controlling factors could include nutritional composition and intestinal mucus composition, as well as environmental factors, such as antibiotics. We introduce a modeling framework of a metabolically realistic intestinal microbial ecology in which hypothetical scenarios can be tested and compared. We present simulations that suggest that greater levels of intra-intestinal oxygenation more strongly delay the dominance of Bifidobacterium species, explaining the observed variety of microbial composition and demonstrating the use of the model for hypothesis generation. The framework allows us to test a variety of controlling factors, including intestinal mixing and transit time. Future versions will also include detailed modeling of oligosaccharide and mucin metabolism.

systems biology↗