Biology subjects

Van de Wiele, T.

Publications and source records attributed to Van de Wiele, T..

8 recordsLinked to original sources

bioRxiv2026

Multi-omics Analyses of Facial Skin in Acne Identify Distinct Microbial and Metabolic Features at Lesional and Non-lesional Sites

The microbial and biochemical landscape of clinically normal-appearing skin in individuals with acne remains uncharacterized. Here, we performed longitudinal multi-omics profiling of facial skin from 10 individuals with moderate acne and 10 healthy controls, integrating 16S rRNA gene sequencing, shotgun metagenomics, and untargeted metabolomics across lesional and non-lesional sites. Compositional tensor factorization revealed that non-lesional acne skin occupies a distinct intermediate state between healthy and lesional skin in both the microbiome and the metabolome. Machine learning models distinguished healthy from non-lesional acne skin with 70% accuracy, demonstrating that molecular dysbiosis occurs in areas of the skin without visible lesions. Non-lesional sites exhibited reduced microbial diversity, strain-level shifts in Corynebacterium and Lawsonella correlating with disease severity, and metabolic alterations, including elevated lipids and perturbed amino acid and dipeptide profiles. Microbe-metabolite co-occurrence network analyses revealed that healthy skin is enriched for protective metabolites such as urocanic acid, while acne-associated skin shows distinct co-occurrence patterns. These findings establish that acne represents a field effect disorder, with molecular alterations extending beyond visible lesions to encompass the entire facial skin ecosystem. This molecular signature of pre-lesional skin provides potential biomarkers for early intervention and suggests that effective acne treatment may require holistic approaches targeting the broader skin environment rather than individual lesions alone.

microbiology↗

bioRxiv2024

GelMA as scaffold material for epithelial cells to emulate the small intestinal microenvironment.

Host-microbe interactions in the intestine play a significant role in health and disease. Novel scaffolds for host cells, capable of potentially supporting ese intricate interactions, are necessary to improve our current systems for mimicking host-microbiota interplay in vitro/ex vivo. In this research paper, we study the application of gelatin methacrylamide (GelMA) as scaffold material for intestinal epithelial cells in terms of permeability, mechanical strength, and biocompatibility. We investigated whether the degree of substitution (DS) of GelMA influences the permeability and found that both high and low DS GelMA show sufficient permeability of biorelevant transport markers. Additionally, we researched epithelial cell adherence and viability, as well as mechanical characteristics of different concentrations of GelMA. All concentrations of hydrogel show long-term biocompatibility for the mono- and co-cultures, despite the goblet-like cells (LS174T) showing lower performance than enterocyte-like cells (Caco-2). The mechanical strength of all hydrogel concentrations was in a physiologically relevant range to be used as scaffold material for intestinal cells. Based on these results, we conclude that GelMA is a suitable material as a scaffold for intestinal cell types in terms of permeability, mechanical strength and biocompatibility. These findings contribute to the growing field of in vitro modeling of the gut and moves the field further to ensuring more translatable research on host-microbe interactions.

bioengineering↗

bioRxiv2021

Long term exposure of human gut microbiota with high and low emulsifier sensitivity to soy lecithin in M-SHIME model.

In the context of the potential health hazards related to food processing, dietary emulsifiers have been shown to alter the structure and function of the gut microbial community, both in vivo and in vitro. In mouse models, these emulsifier exposed gut microbiota were shown to contribute to gut inflammation. Several knowledge gaps remain to be addressed though. As such, the impact from a longer timeframe of exposure on the gut microbiota is not known and interindividual variability in microbiome response needs to be measured. To answer these research questions, in this study the faecal microbiota from two individuals, previously selected for high and low emulsifier sensitivity, were exposed to two concentrations of soy lecithin during a 7 day treatment phase in the dynamic mucosal simulator of the human intestinal microbial ecosystem (M-SHIME). The results showed mild effects from soy lecithin on the composition and functionality of these microbial communities, which depended on the original microbial composition. The effects also mostly levelled off after 3 days of exposure. The emulsifier sensitivity for which the microbiota were selected, was preserved. Some potentially concerning effects were also registered: butyrate levels, positively correlating with Faecalibacterium abundance, were lowered by soy lecithin. Also the abundance of the beneficial Bifidobacterium genus was lowered, while the abundance of the notorious unclassified Enterobacteriaceae was increased. Within the family of the unclassified Lachnospiraceae, several genera were either suppressed or stimulated. The effects that these microbial alterations would have on a living host is not yet certain, especially given the fact that large fractions of soy lecithins constituents can be absorbed. Nevertheless, choline and phosphatidylcholine, both primary and absorbable constituents of soy lecithin, have recently been linked to cardiovascular disease via the generation of TMA by the gut microbiota. Further studies that validate our findings and link them to potential health outcomes are thus justified.

microbiology↗

bioRxiv2021

Differential impact of rhamnolipids and polysorbate80 on composition and functionality of the gut microbiota in the SHIME system.

Dietary emulsifiers have been shown to affect the composition and function of the gut microbial community, both in vivo and in vitro. Yet, several knowledge gaps remain to be addressed: the impact from a longer timeframe exposure on the gut microbiota, interindividual variability in microbiome response and the putative impact from novel clean label alternatives for current food emulsifiers. In the present study, the impact of one conventional dietary emulsifier, TWEEN80, and one potential novel alternative, rhamnolipids, on the human gut microbiota was investigated using the Mucosal Simulator of the Human Intestinal Microbial Ecosystem (M-SHIME). The faecal microbiota from two human donors, with high and low responsiveness to the emulsifiers, were exposed to 0,05 m% and 0,5 m% of the emulsifiers for 7 days. The results confirmed previous observations that the effects on the composition and functionality are both emulsifier- and donor dependent. The effects reached an equilibrium after about 3 days of exposure. Overall, TWEEN80 and rhamnolipids displayed opposite effects: TWEEN80 increased cell counts, reduced propionate concentration, increased butyrate levels, increased a.o. Faecalibacterium, Blautia and Hungatella abundance, while rhamnolipids did the opposite. Rhamnolipids also sharply increased the abundance of unclassified Lachnospiraceae. On the other hand, both emulsifiers increased the relative abundance of unclassified Enterobacteriaceae. Both emulsifiers also altered the microbial metabolome in different ways and a pathway enrichment analysis tool revealed that the metabolome alterations could be reminiscent of gut issues and obesity. Overall, the impact from the rhamnolipids was larger than that of TWEEN80 at similar concentrations, indicating that the former may not necessarily be a safer alternative for the latter. The microbiotas response also depended on its original composition and the sensitivity status for which the faecal donors were selected, was preserved. Whether the same donor-diversity and longitudinal impact can be expected in the human colon as well and what impact this has on the host will have to be further investigated.

microbiology↗

bioRxiv2020

Dietary emulsifiers alter composition and activity of the human gut microbiota in vitro, irrespective of chemical or natural emulsifier origin.

The use of additives in food products has become an important public health concern. In recent reports, dietary emulsifiers have been shown to affect the gut microbiota, contributing to a pro-inflammatory phenotype and metabolic syndrome. So far, it is not yet known whether similar microbiome shifts are observable for a more diverse set of emulsifier types and to what extent these effects vary with the unique features of an individuals microbiome. To bridge this gap, we investigated the effect of five dietary emulsifiers on the fecal microbiota from 10 human individuals upon a 48 hour exposure. Community structure was assessed with quantative microbial profiling, functionality was evaluated by measuring fermentation metabolites and pro-inflammatory properties were assessed with the phylogenetic prediction algorythm PICRUSt, together with a TLR5 reporter cell assay for flagellin. A comparison was made between two mainstream chemical emulsifiers (carboxymethylcellulose and P80), a natural extract (soy lecithin) and biotechnological emulsifiers (sophorolipids and rhamnolipids). While fecal microbiota responded in a donor-dependent manner to the different emulsifiers, profound differences between emulsifier were observed. Rhamnolipids, sophorolipids and soy lecithin eliminated 91% {+/-} 0%, 89% {+/-} 1% and 87% {+/-} 1% of the viable bacterial population after 48 hours, yet they all selectively increased the proportional abundance of putative pathogens. Moreover, profound shifts in butyrate (-96% {+/-} 6 %, -73% {+/-} 24% and -34 {+/-} 25% respectively) and propionate (+13% {+/-} 24 %, +88% {+/-} 50% and +29% {+/-} 16% respectively) production were observed for these emulsifiers. Phylogenetic prediction indicated higher motility, which was, however, not confirmed by increased flagellin levels using the TLR5 reporter cell assay. We conclude that dietary emulsifiers can severely impact the gut microbiota and this seems to be proportional to their emulsifying strength, rather than emulsifier type or origin. As biotechnological emulsifiers were especially more impactful than chemical emulsifiers, caution is warranted when considering them as more natural alternatives for clean label strategies.

microbiology↗

bioRxiv2019

Short-term celecoxib supplementation impacts compositional and functional features of in vitro gut microbial ecosystem

Celecoxib has been demonstrated effective in the prevention and treatment of chronic inflammatory disorders through inhibition of altered cyclooxygenase-2 (COX-2) pathways. Despite the benefits for preventing colorectal cancer (CRC), continuous administration may increase risk of cardiovascular events. Understanding microbiome-drug-host interactions is fundamental for improving drug disposition and safety responses of colon-targeted formulations, but little information is available on the bidirectional interaction between individual microbiomes and celecoxib. Here we conducted in vitro batch incubations of faecal microbiota to evaluate the short-term impact of celecoxib on activity and composition of colon bacterial communities. Celecoxib-exposed microbiota shifted metabolic activity and community composition, whereas total transcriptionally active bacterial population was not significantly changed. Butyrate production decreased by 50% in a donor-dependent manner, suggesting that celecoxib impacts in vitro fermentation. Microbiota-derived acetate has been associated with inhibition of cancer markers and our results suggest uptake of acetate for bacterial functions when celecoxib was supplied, which potentially favoured bacterial competition for acetyl-CoA. We further assessed whether colon microbiota modulates anti-inflammatory efficacy of celecoxib using both a simplified inflammation model, and a novel in vitro simulation of the enterohepatic metabolism. Celecoxib was responsible for only 5% of the variance in bacterial community composition but celecoxib-exposed microbiota preserved barrier function and decreased concentrations of IL-8 and CXCL16 in a donor-dependent manner in our two cell models simulating inflammatory milieu in the gut. Our results suggest that celecoxib-microbiome-host interactions may not only elicit adaptations in community composition but also in microbiota functionality and may need to be considered for guaranteeing efficient COX-2 inhibition.\n\nIMPORTANCEAs inter-individual changes in the microbiome composition and functionality may be a confounder on pharmacotherapy, we obtained mechanistic understanding on how short-term celecoxib exposure impacts the functional activities of colon communities. Celecoxib-exposed microbiota shifted metabolic activity without impacting numbers of total active bacteria, but only community composition. Thus, increased relative abundance of particular genera during celecoxib supplementation may just indicate changes in maintenance energy. Focus on the influence of acetyl-CoA on cancer cells and verifying whether changes in acetate:propionate:butyrate ratios rather than in taxonomic diversity can be used as markers of decreased inflammation may be the next frontiers for predicting successful NSAID therapy, and ultimately for developing microbiome-based therapies.

microbiology↗

bioRxiv2019

Specific targeting of intestinal Prevotella copri by a Listeria monocytogenes bacteriocin

Deciphering the specific function of every microorganism in microbial gut communities is a key issue to interrogate their role during infection. Here, we report the discovery of a Listeria bacteriocin, Lmo2776, that specifically targets the abundant gut commensal Prevotella copri and affects Listeria infection. Oral infection of conventional mice with a {Delta}lmo2776 mutant leads to a thinner intestinal mucus layer and higher Listeria loads both in the intestinal content and deeper tissues compared to WT Listeria, while no difference is observed in germ-free mice. This microbiota-dependent effect is phenocopied by precolonization of germ-free mice before Listeria infection, with P. copri, but not with other commensals. Together, these data unveil a role for Prevotella in controlling intestinal infection, highlighting that pathogens may selectively deplete microbiota to avoid excessive inflammation.

microbiology↗

bioRxiv2018

The smallest intestine (TSI) - a low volume in vitro model of the small intestine with increased throughput

AimsTo develop a low volume in vitro model with increased throughput simulating the human small intestine, incorporating the presence of ileal microbiota, to study microbial behaviour in the small intestine.\n\nMethods and ResultsThe Smallest Intestine in vitro model (TSI) was developed. During the simulated passage of the small intestine bile is absorbed by dialysis and pH adjusted to physiologically relevant level. A consortium of seven representative bacterial members of the ileum microbiota is included in the ileal stage of the model. It was found that the model can be applied for the testing of survival of probiotic bacteria in upper intestine. Moreover, it was found, that the presence of the ileal microbiota significantly impacted probiotic survival.\n\nConclusionsTSI allows testing a substantial number of samples, at low cost and short time, and is thus suitable as an in vitro screening platform. Multiples of five reactors can be added to increase the number of biological and technical replicates.\n\nSignificance and Impact of the StudyTSI serves as an alternative for costly and low throughput in vitro models currently existing on the market. Above that, significance of small intestine bacteria presence on survival of probiotic bacteria in the upper intestine was proved.

microbiology↗