Enhanced Stability and Function of Probiotic Streptococcus thermophilus with Self-Encapsulation by Increasing the Biosynthesis of Hyaluronan

Abstract

The harsh conditions of the gastrointestinal tract limit the potential health benefits of oral probiotics. It is promising that oral bioavailability is improved by strengthening the selfprotection of probiotics. Here, we report the encapsulation of a probiotic strain by endogenous production of hyaluronan to enhance the effects of oral administration of the strain. The traditional probiotic Streptococcus thermophilus was engineered to produce hyaluronan shells by using traceless genetic modifications and clustered regularly interspaced short palindromic repeat interference. After oral delivery to mice in the form of fermented milk, hyaluronan-coated S. thermophilus (204.45 mg/L hyaluronan in the milk) exhibited greater survival and longer colonization time in the gut than the wild-type strain. In particular, the engineered probiotic strain could also produce hyaluronan after intestinal colonization. Importantly, S. thermophilus self-encapsulated with hyaluronan increased the number of goblet cells, mucus production, and abundance of the microorganisms related to the biosynthesis of short-chain fatty acids, resulting in the enhancement of the intestinal barrier. The coating formed by endogenous hyaluronan provides an ideal reference for the effective oral administration of probiotics.

Intestinal Delivery of Probiotics: Materials, Strategies, and Applications

“…Paracasei (L. paracasei subsp. Paracasei), [90,91] Bifidobacterium, [92][93][94] Streptococcus thermophilus, [95] and Pediococcus pentosaceus. [96] Although many of them are derived from the gut of healthy individuals or traditional fermented foods, nowadays, the newly explored resident microorganisms in human are considered by researchers as live biotherapeutics, identified as next-generation probiotics (NGPs), such as Akkermansia, [97,98] Faecalibacterium prausnitzii (F. prausnitzii), [99,100] and Bacteroides fragilis (B. fragilis).…”

“…Pickering high internal phase emulsions (HIPEs); biofilms [85,88] Lactobacillus rhamnosus Ameliorating enteritis; enhancing resistance of probiotics to gastric pH and realizing the on-demand release of probiotics Hyaluronic acid-based hydrogel; exfoliated bentonite/alginate nanocomposite hydrogel [78,87] Lactobacillus reuteri Wound healing Methacrylate-modified hyaluronic acid (HA) [34] Bifidobacterium bifidum Photothermal cancer immunotheranostics Indocyanine green (ICG) encapsulating Cremophor EL (CRE) nanoparticles [93] Bifidobacterium breve Protection against gastrointestinal fluids and antibiotics Protamine-assisted SiO 2 nanoparticle yolk−shell packing, alginate gelation, and zinc-salt-based metal-organic framework (ZIF-8) mineralization [92] Streptococcus thermophilus Enhancing stability and function Endogenous production of hyaluronan [95] Lactococcus lactis Improving gastric acid resistance and adhesive colonization Thiolated oxidized konjac glucomannan microspheres [108] Pediococcus pentosaceus Clostridium difficile infection treatment Alginate-starch microgels [96] Nonconventional Saccharomyces cerevisiae -Nanostructured silica matrices [59] Escherichia coli In vivo tumor imaging; treating intestinal mucositis; treating gastrointestinal tract-related diseases; treating colitis Cell membrane; silk fibroin; tannic acid (TA) and Eudragit L100; dopamine and chitosan; nanozyme [21,[71][72][73][74] Bacillus Treating metabolic syndrome Alginate [89] Clostridium butyricum Regulating gut microbiota and suppressing colon cancer Dextran [32] Next-generation…”