Amyloid–Polyphenol Hybrid Nanofilaments Mitigate Colitis and Regulate Gut Microbial Dysbiosis

Abstract

It is a desirable and powerful strategy to precisely fabricate functional soft matter through self-assembly of molecular building blocks across a range of length scales. Proteins, nucleic acids, and polyphenols are the self-assemblers ubiquitous in nature. Assembly of proteins into flexible biocolloids, amyloid fibrils with high aspect ratio, has emerged as an unchallenged templating strategy for high-end technological materials and bio-nanotechnologies. We demonstrate the ability of these fibrils to support the deposition and self-assembly of polyphenols into hybrid nanofilaments and functional macroscopic hydrogels made thereof. The length scale of the substance that amyloid fibrils can attach with acting as the building templates was extended from nanometer down to sub-nanometer. Significantly increased loading capacities of polyphenols (up to 4.0 wt %) compared to that of other delivery systems and improved stability were realized. After oral administration, the hydrogels could transport from the stomach to the small intestine and finally to the gut (cecum, colon, rectum), with a long retention time in the colon. Oral administration of the hydrogels significantly ameliorated colitis in a mouse model, promoted intestinal barrier function, suppressed the pro-inflammatory mRNA expression, and very significantly (P < 0.01) regulated gut microbial dysbiosis. Specifically, it reduced the abundance of normally enriched operational taxonomic units related to colitis, especially targeting facultative anaerobes of the phylum Proteobacteria, such as Aestuariispira and Escherichia. The short-chain fatty acid metabolites were enriched. Combined with their nontoxic nature observed in this long-term study in mice, the obtained amyloid–polyphenol gels have high application potentials for gastrointestinal diseases by “drugging the microbiome”.

Redox-active nanoparticles for inflammatory bowel disease

“…Hu et al constructed amyloid-polyphenol hybrid nanofilment hydrogels with higher EGCG loading capacity than other delivery systems (Fig. 9(a)) [50]. After oral administration, the hydrogel could enter the small intestine from the stomach, finally enter the large intestine and remain in the colon for a long time (Fig.…”

“…The mechanism of intimate interactions between redox-active NPs and gut microbiota is closely associated with ROS/RNS. Studies have brought evidence that NPs-mediated ROS/RNS scavenging can interfere with the respiration of pathogenic bacteria (Proteobacteria) induced by IBD, thereby reducing the relative abundance of pathogenic bacteria and restoring the homeostasis of gut microbiota [50]. However, some redoxactive NPs are known as ROS/RNS generators, and oxidative Figure 1 The relationship between IBD, ROS/RNS and gut microbiota.…”

On Concept of Hybrid in Colloid Sciences

“…Given the possibility to get tailored species, mostly in terms of surface functionalities, release capacity, and bio-compatibility, many have tried getting formulations capable of operating at the gut level [99], gene silencing [100], bone tissue regeneration [101][102][103], preparing devices [104] and/or decorating NPs with human stem cells [105], and anticancer therapy [106], as well. We do not know exactly how efficient the mentioned formulations are compared to canonical ones, but it expected that their safe use is close to be effective in vivo.…”

Pleurotus Ostreatus β-glucan Alleviates Cyclophosphamide-induced Immunosuppression by Regulating Gut Microbiota in Mice

“…The damage to intestinal mucosal barrier can cause the reduced secretion of immunoglobulins and impaired function of immune organs, thereby diminishing an immune response [2]. The gut microbiota, a complex community consisting of over 100 trillion bacteria in the distal gut, and their metabolites constitute the chemical and biological barriers of intestinal mucosa [3]. The previous report indicated that speci c bacterial phylotypes were parallel to the expression of tight junction proteins, but impaired intestinal mucosal barrier could induce bacterial translocation [4].…”