Biology subjects

Kadibalban, A. S.

Publications and source records attributed to Kadibalban, A. S..

4 recordsLinked to original sources

bioRxiv2025

Genome-scale metabolic models predict diet- and lifestyle-driven shifts of ecological interactions in the gut microbiome

1.Microbiomes and their host environments form complex, interconnected ecosystems. The microbial species within a microbiome, on the one hand, compete for resources, while on the other hand, they exchange vital metabolites to support their survival. These interactions are influenced by the microbial genetic repertoire, environmental conditions, and the availability of nutrients. We developed EcoGS (http://www.github.com/KaletaLab/EcoGS), a metabolic modelling tool designed to predict ecological interactions between pairs of microbes. Applying EcoGS to the microbiomes of two distinct human cohorts revealed a shift from collaborative to exploitative ecological interactions associated with higher dietary intake of simple sugars (glucose and fructose), in diabetic individuals and those living in industrialised lifestyles. On the other hand, the consumption of Cobalamin (vitamin B12), phylloquinone (vitamin K1) and biotin (vitamin B7), among other compounds, was associated with increased collaboration in the gut microbiome. We conclude that the abundance of simple sugars as an energy source reduces the necessity for microbes to cooperate, thereby increasing competition and hostility among microbiome members. Moreover, our study proposes multiple compounds, such as urate, deoxyadenosine, deoxyguanosine, and hypoxanthine, for in vitro validation tests as dietary interventions that have the potential to restore the ecological balance amongst the community. EcoGS serves as a valuable tool for exploring microbiome dynamics and their connections to environmental changes and disease.

systems biology↗

bioRxiv2024

Metabolic modeling reveals a multi-level deregulation of host-microbiome metabolic networks in IBD

Inflammatory bowel diseases (IBDs) are chronic disorders involving dysregulated immune responses. Despite the role of disrupted host-microbial interaction in the pathophysiology of IBD, the underlying metabolic principles are not fully understood. We densely profiled microbiome, transcriptome and metabolome signatures from longitudinal IBD cohorts before and after advanced drug therapy initiation and reconstructed metabolic models of the gut microbiome and the host intestine to study host-microbiome metabolic cross-talk in the context of inflammation. We identified concomitant changes in metabolic activity across data layers involving NAD, amino acid, one-carbon and phospholipid metabolism. In particular on the host level, elevated tryptophan catabolism depleted circulating tryptophan, thereby impairing NAD biosynthesis. Reduced host transamination reactions disrupted nitrogen homeostasis and polyamine/glutathione metabolism. The suppressed one-carbon cycle in patient tissues altered phospholipid profiles due to limited choline availability. Simultaneously, microbiome metabolic shifts in NAD, amino acid and polyamine metabolism exacerbated these host metabolic imbalances. Leveraging host and microbe metabolic models, we predicted dietary interventions remodeling the microbiome to restore metabolic homeostasis, suggesting novel therapeutic strategies for IBD.

systems biology↗

bioRxiv2024

Metabolic modelling reveals increased autonomy and antagonism in type 2 diabetic gut microbiota

1.Type 2 diabetes presents a growing global health concern, with emerging evidence highlighting the pivotal role of the human gut microbiome in metabolic diseases. This study employs metabolic modelling to elucidate changes in host-microbiome interactions in type 2 diabetes. Glucose levels, dietary intake, 16S sequences and metadata were estimated and collected for a cohort of 1,866 individuals. In addition, microbial community models, as well as ecological interactions were simulated for the gut microbiomes of the cohort participants. Our findings revealed a significant decrease in the fluxes of metabolites provided by the host to the microbiome through the diet in patients with type 2 diabetes, accompanied by an increase in within-community exchanges. Moreover, the diabetic microbial community shifts towards increased exploitative ecological interactions among its member species at the expense of collaborative interactions. The reduced butyrate flux from the community to the host and reduced tryptophan acquired by the microbiome from the hosts diet further highlight the dysregulation in microbial-host interactions in diabetes. Additionally, microbiomes of type 2 diabetes patients exhibit enrichment in energy metabolism pathways, indicative of increased metabolic activity and antagonism. This study provides insights into the metabolic dynamics of the diabetic gut microbiome, shedding light on its increased autonomy and altered ecological interactions accompanying diabetes, and provides candidate metabolic targets for intervention studies and experimental validations, such as butyrate, tryptophan, H2S, several nucleotides, amino acids, and B vitamins.

systems biology↗

bioRxiv2024

Metabolic modeling reveals the aging-associated decline of host-microbiome metabolic interactions in mice

Aging is the predominant cause of morbidity and mortality in industrialized countries. The specific molecular mechanisms that drive aging are poorly understood, especially the contribution of the microbiota in these processes. Here, we combined multi-omics with metabolic modeling in mice to comprehensively characterize host-microbiome interactions and how they are affected by aging. Our findings reveal a complex dependency of host metabolism on microbial functions, including previously known as well as novel interactions. We observed a pronounced reduction in metabolic activity within the aging microbiome, which we attribute to reduced beneficial interactions in the microbial community and a reduction in its metabolic output. These microbial changes coincided with a corresponding downregulation of key host pathways predicted by our model to be dependent on the microbiome that are crucial for maintaining intestinal barrier function, cellular replication, and homeostasis. Our results elucidate microbiome-host interactions that potentially influence host aging processes, focusing on microbial nucleotide metabolism as a pivotal factor in aging dynamics. These pathways could serve as future targets for the development of microbiome-based therapies against aging. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=196 SRC="FIGDIR/small/587009v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@a8e7faorg.highwire.dtl.DTLVardef@115f35aorg.highwire.dtl.DTLVardef@1bbf32org.highwire.dtl.DTLVardef@1a58c7f_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗