bioRxiv Science⌕ Search

bioRxiv · 10.1101/2024.10.15.618493

Activated carbon ameliorates type 2 diabetes via metabolic remodeling of the gut microbiota

Abstract

Type 2 diabetes (T2D) is a major public health concern worldwide and there has been increasing attention on the role of natural dietary drugs in diabetes therapy. However, the effects of these drugs on gut microbial composition, functional potentials and metabolisms remain unclear. Here, we conducted integrated 16S rRNA sequencing and metabolomic analyses in T2D GK rats and healthy Wistar rats that exposed to four natural dietary drugs (highly porous activated carbon, wheatgrass, dandelion and corn stigma). Oral administration of activated carbon and dandelion decreased the body weight gain in both high-fat diet (HFD) GK rats and Wistar rats. Significantly lower level of blood glucose was observed in GK rats with activated carbon intervention. A group of beneficial bacteria and metabolites were promoted, and the endotoxin-producing bacteria were inhibited by dietary drugs, especially for the activated carbon diet. Oral administration of activated carbon resulted in metabolic changes and anti-inflammatory effects that decreased both high-fat diet-induced obesity and diabetes. The beneficial effects of increased positive responders are related to improved carbohydrate and amino acid metabolism, regulated inflammatory mediators, with simultaneous reduction of detrimental compounds such as lipopolysaccharide (LPS) synthesis and modification of the gut microbiome. These findings highlight the effectiveness of natural dietary drugs, with a particular emphasis on activated carbon, and establish a foundation for tailoring the use of these drugs in T2D therapy. ImportanceOur findings highlight the significant hypoglycemic effect of activated carbon, demonstrating its potential to remodel the gut microbiota, improve carbohydrate and amino acid metabolism, regulate inflammatory mediators, and reduce detrimental compounds such as lipopolysaccharide (LPS). These results suggest that dietary intervention with activated carbon could be a noninvasive and accessible method for improving diabetes management, providing novel insights into the role of natural dietary drugs in metabolic health and diabetes therapy.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Zhao, C.-X., Wu, Y., Guo, X., Wang, Y., Su, J.-Q.. 2024-10-16. Activated carbon ameliorates type 2 diabetes via metabolic remodeling of the gut microbiota. https://doi.org/10.1101/2024.10.15.618493

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

A population-scale landscape of the subgingival microbiome reveals divergent routes to periodontal dysbiosis

Periodontitis is an archetypical mucosal inflammatory disease in which microbiome dysbiosis at the tooth-epithelial interface interacts with host genetic and behavioral risk factors to drive immune-mediated tissue destruction. Although subgingival microbiome compositional shifts are thought to parallel disease severity, microbiome variation at the population-level and its relationship to periodontal clinical phenotypes and disease-modifying factors remain poorly defined. Here, we use unsupervised manifold learning to map the compositional landscape of the subgingival microbiome in 1,355 adults spanning periodontal health to severe periodontitis. We identified eight latent microbiome states organized along a branching continuum from eubiosis to dysbiosis. An intermediate microbial configuration marked ecological destabilization and bifurcation into two distinct periodontitis-associated dysbiotic trajectories, distinguished by links to gingival inflammation and smoking. Although the microbiome trajectories broadly tracked periodontal destruction, a minority of individuals showed discordant microbiome-clinical phenotypes, with some individuals with periodontitis retaining otherwise eubiotic microbiomes enriched for low-abundance pathobionts, while some cases of health or mild disease had highly dysbiotic communities, suggesting distinct host susceptibility. Together, these findings define a population-scale ecological landscape of the subgingival microbiome, reveal divergent trajectories to periodontal dysbiosis, and highlight heterogeneity in the relationship between microbial community structure and clinical disease expression.

microbiology↗

The iron-binding siderophore enterobactin is required for the response of multi-drug resistant Klebsiella pneumoniae to zinc limitation

To persist during infection Klebsiella pneumoniae must overcome nutrient iron and zinc limitation imposed by the host immune system through a process called nutritional immunity. Secreted small molecule siderophores are a major virulence determinant of Klebsiella pneumoniae pathogenesis and are presumed to overcome nutritional immunity by binding iron for bacterial acquisition. In this work, we set out to identify how a multi-drug resistant K. pneumoniae grows in zinc limited environments. Using unbiased transcriptomics, proteomics, and an arrayed transposon screen, we identified that synthesis and uptake of the siderophore enterobactin is required to allow for growth in low zinc conditions. Iron-specific chelators did not replicate this phenotype and addition of supplemental iron through heme in growth media could not complement severe growth defects of enterobactin mutant K. pneumoniae experiencing zinc limitation. Finally, zinc starvation induced enterobactin production independent of the canonical zinc uptake regulator (Zur) transcription factor suggesting an unidentified regulatory mechanism by which Gram-negative pathogens may respond to zinc stress. Together, these studies expand the role of enterobactin beyond iron regulation and highlight a previously unreported link between iron and zinc homeostasis in Klebsiella pneumoniae.

microbiology↗

A microbiota-derived protease links phage susceptibility to host epithelial responses

Bacteriophages are major ecological drivers of gut microbial ecology, yet whether bacterial mechanisms that determine phage susceptibility have consequences for the mammalian host remains poorly understood. Here, we identify dipeptidyl peptidase 11 (Dpp11a), the predominant active serine protease of the prevalent gut commensal Phocaeicola vulgatus, as an unexpected bacterial defence factor. Dpp11a protects against environmental proteases and confers resistance to bacteriophage infection. Metatranscriptomic analyses further reveal increased expression of both dpp11a and P. vulgatus-associated phage transcripts in ulcerative colitis stool samples, indicating that both components of this interaction are transcriptionally active in disease-associated human microbiomes. Using the microfluidic gut-on-a-chip co-culture model HuMiX, we show that the absence of Dpp11 is accompanied by altered epithelial tight-junction remodelling during phage-bacterial infection. Together, our findings reveal that the consequences of bacterial phage defence can extend beyond phage-bacterium interactions to the mammalian epithelium.

microbiology↗