bioRxiv Science⌕ Search

bioRxiv · 10.1101/2021.06.11.447961

Daily transient coating of the intestine leads to weight loss and improved glucose tolerance

Abstract

The worsening obesity epidemic has driven a parallel increase in incidence of type-2 diabetes (T2D) found in 13% of the adult US population. Roux-en-Y gastric bypass surgery (RYGB) is the golden standard surgical treatment for obesity-related T2D. However, over 70% of T2D patient do not meet the NIH criteria for surgery, and many that do, are reluctant to consider such an invasive intervention. Mechanisms behind the antidiabetic effect of RYGB are not clearly understood, but isolation of proximal bowel from nutrient exposure plays a critical role. In this study, we tested the impact of daily administration of an oral gut coating agent, LuCI (Luminal Coating of the Intestine), in controlling weight and insulin resistance. LuCI is not systemically absorbed and provides a transient coating of the proximal intestines and excludes the coated bowel from nutrient contact, thus mimicking the effects of RYGB. We demonstrate that LuCI results in weight loss and improved insulin sensitivity in a rat DIO model. LuCI also appears to replicate hormonal changes seen after RYGB, by increasing post-prandial GLP-1 and GIP levels. LuCI has the potential to replicate the metabolic benefit of surgery and be a novel therapeutic strategy for obesity associated T2D.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Lo, T., Lee, Y., Tseng, C.-Y., Hu, Y., Mantzoros, C., Karp, J., Tavakkoli, A.. 2021-06-11. Daily transient coating of the intestine leads to weight loss and improved glucose tolerance. https://doi.org/10.1101/2021.06.11.447961

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

KEEP EXPLORING

Related preprints

Single-Component Photo-Crosslinked Lipoic Acid Functionalized Mucin Hydrogels: Dynamic Mucus Mimetics for Antiviral Protection

Native mucus protects epithelial surfaces through viscoelastic networks of disulfide-linked mucins. However, commercially available mucins often fail to reconstitute comparable mechanical and barrier properties, while synthetic and hybrid mucus mimetics require polymeric crosslinkers that may alter mucus-like composition. Inspired by the native architecture, we directly functionalized porcine gastric and bovine submaxillary mucins with -lipoic acid to develop a single-component, photo-crosslinkable hydrogels. Upon UV irradiation (365 nm), the modified mucins rapidly form disulfide-crosslinked networks without added photo-initiator/ polymeric crosslinkers, two orders of magnitude faster as compared with PEG-SH approaches. The resulting mucin-lipoic acid (MUC-LA) hydrogels exhibit mucus-relevant properties, including tunable viscoelasticity, redox responsiveness, self-healing, and size-dependent restrictions on nanoparticle transport. In transwell-based infection models, MUC-LA hydrogels (2-3%) mimicking the healthy airway mucus (G' {approx} 10-20 Pa) suppress epithelial infection by SARS-CoV-2 and influenza A virus. Crosslinked MUC-LA provides greater protection against SARS-CoV-2 than the non-crosslinked, whereas both formulations suppress influenza A infection, suggesting distinct contributions from network formation and mucin-associated interactions. These findings establish a dynamic, mucus-mimetic platform integrating rapid photo-gelation, controllable mechanics, selective transport, and antiviral barrier functionality. MUC-LA hydrogels offer opportunities to investigate mucosal transport and host-pathogen interactions, with potential applications in drug delivery, and as biomaterials.

bioengineering↗

A Fibrous Optofluidic Probe for Endovascular Sensing of Blood Oxygenation and Flow Velocity

Local hemodynamic information including blood oxygenation and flow velocity could guide vascular interventions, yet obtaining these parameters in deep, narrow vessels remains challenging. Here, we report a flexible, submillimeter-scale fibrous optofluidic probe for endovascular sensing of blood oxygenation and flow velocity. The probe integrates a polymer optical fiber for light transmission with a microfluidic tube for dye injection, enabling spectroscopic oximetry and fluorescence dilution-based velocimetry through a single device. Via vascular intervention, we demonstrate local hemodynamic sensing in rabbit arteries and angiography-guided deployment in canine carotid arteries. The probe captures local changes in blood oxygenation and flow velocity during vascular occlusion and reperfusion, revealing hemodynamic disturbances that are not reflected in peripheral monitors. These results illustrate the complementary information provided by local oximetry and velocimetry and establish a compact optofluidic platform for quantitative hemodynamic monitoring during vascular interventions.

bioengineering↗

Broad-spectrum in situ genetic reprogramming of native microbiomes

Complex microbial communities are found throughout terrestrial, aquatic, and animal-associated ecosystems. Genetic modification of discrete microbial taxa within native communities represents a powerful tool to study and augment microbiome functions. Herein, we develop Synthetic Phage Assisted Reprogrammable and Targetable Addition (SPARTA) as a one-step strategy for packaging, delivering, and integrating large synthetic DNA into a broad range of native microbiomes. SPARTA leverages a broad-spectrum synthetic phage particle for in situ genome engineering within complex soil, freshwater, and mammalian fecal microbiomes, reprogramming 59 native species across 16 families. By modulating SPARTA components, we further demonstrated tunability of SPARTA towards targeted microbiome population. Additionally, we built a novel companion tool to quantitatively identify engineered taxa, named 16S crRNA-guided inference of bacterial engineering sequencing or ScRibe-seq. The SPARTA-ScRibe-seq pipeline delivered and validated functional synthetic gene clusters in diverse native microbiomes while preserving the original microbial community structure. Together, this novel genome engineering framework constitutes an end-to-end programmable platform for rational and customizable reprogramming of native microbiomes.

bioengineering↗