A Multiscale Spatiotemporal Model Including a Switch from Aerobic to Anaerobic Metabolism Reproduces Succession in the Early Infant Gut Microbiota

Versluis, David M.; Schoemaker, Ruud; Looijesteijn, Ellen; Muysken, Daniël; Jeurink, Prescilla V.; Paques, Marcel; Geurts, Jan M.W.; Merks, Roeland

doi:10.1128/msystems.00446-22

Cited by 10 publications

(31 citation statements)

References 86 publications

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“…To develop new hypotheses on how oligosaccharides can stimulate the production of butyrate, we further develop a multiscale metabolic model (Fig. 1A & B) of the carbon metabolism of the infant gut microbiota [78]. The computational model is based upon our earlier models of the adult and infant microbiota [75, 78].…”

Section: Resultsmentioning

confidence: 99%

“…1A & B) of the carbon metabolism of the infant gut microbiota [78]. The computational model is based upon our earlier models of the adult and infant microbiota [75, 78]. In comparison with these previous models, the present model simulates a larger number of small bacterial populations, using a larger, more diverse, and further curated set of metabolic models of gut bacteria from the AGORA database [44].…”

Section: Resultsmentioning

confidence: 99%

“…The enzymatic constraint is determined by the local population size. This approach allows us to model metabolic switches and trade-offs [45, 78]. The FBA solution includes a set of influx rates and efflux rates of metabolites that are used to update the environmental metabolite concentrations.…”

Section: Resultsmentioning

confidence: 99%

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2’-Fucosyllactose helps butyrate producers outgrow competitors in infant gut microbiota simulations

Versluis

Schoemaker

Looijesteijn

et al. 2023

Preprint

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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2’-Fucosyllactose helps butyrate producers outgrow competitors in infant gut microbiota simulations

Versluis

Schoemaker

Looijesteijn

et al. 2023

Preprint

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show abstract

“…MiMiC (Kumar et al 2021 )]. An example of a (spatial) simulation of key species of lactose metabolism in infants and the dependency on oxygen is shown in the work of Versluis et al ( 2022 ). The role of SynComs in this quickly expanding endeavor to model the microbiome with GEMs is to use them as a validation because that cannot be done in a natural setting (Weiss et al 2022 ).…”

Section: Emerging Tools Facilitate the Design And Testing Of Syncomsmentioning

confidence: 99%

Synthetic microbial communities (SynComs) of the human gut: design, assembly, and applications

Leeuwen

Brul

Zhang

et al. 2023

FEMS Microbiology Reviews

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The human gut harbors native microbial communities, forming a highly complex ecosystem. Synthetic microbial communities (SynComs) of the human gut are an assembly of microorganisms isolated from human mucosa or fecal samples. In recent decades, the ever-expanding culturing capacity and affordable sequencing, together with advanced computational modeling, started a ‘‘golden age’’ for harnessing the beneficial potential of SynComs to fight gastrointestinal disorders, such as infections and chronic inflammatory bowel diseases. As simplified and completely defined microbiota, SynComs offer a promising reductionist approach to understanding the multi-species and multi-kingdom interactions in the microbe-host-immune axis. However, there are still many challenges to overcome before we can precisely construct SynComs of designed function and efficacy that allow the translation of scientific findings to patients' treatments. Here we discussed the strategies used to design, assemble, and test a SynCom, and address the significant challenges, which are of microbiological, engineering, and translational nature, that stand in the way of using SynComs as live bacterial therapeutics.

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“…Oxygen deficiency induces the anaerobic metabolism which causes the perturbation of intracellular homeostasis, leading to cell destruction and death ( Nguyen et al, 2022 ). When anaerobic metabolism occurs, there are some corresponding changes in cells including decreasing levels of ATP and PH, increasing lactate concentration and ion channels dysfunctions, resulting in intracellular abnormal acidification and hyperosmosis ( Versluis et al, 2022 ). A series of researches had confirmed that curcumin could suppress anaerobic metabolism, maintaining intracellular homeostasis.…”

Section: Curcumin Attenuates Cell Injury During Ischemia Phasementioning

confidence: 99%

Role of curcumin in ischemia and reperfusion injury

Zhang

2023

Front. Pharmacol.

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Ischemia-reperfusion injury (IRI) is an inevitable pathological process after organic transplantations. Although traditional treatments restore the blood supply of ischemic organs, the damage caused by IRI is always ignored. Therefore, the ideal and effective therapeutic strategy to mitigate IRI is warrented. Curcumin is a type of polyphenols, processing such properties as anti-oxidative stress, anti-inflammation and anti-apoptosis. However, although many researches have been confirmed that curcumin can exert great effects on the mitigation of IRI, there are still some controversies about its underlying mechanisms among these researches. Thus, this review is to summarize the protective role of curcumin against IRI as well as the controversies of current researches, so as to clarify its underlying mechanisms clearly and provide clinicians a novel idea of the therapy for IRI.

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A Multiscale Spatiotemporal Model Including a Switch from Aerobic to Anaerobic Metabolism Reproduces Succession in the Early Infant Gut Microbiota

Cited by 10 publications

References 86 publications

2’-Fucosyllactose helps butyrate producers outgrow competitors in infant gut microbiota simulations

2’-Fucosyllactose helps butyrate producers outgrow competitors in infant gut microbiota simulations

Synthetic microbial communities (SynComs) of the human gut: design, assembly, and applications

Role of curcumin in ischemia and reperfusion injury

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