Skin microbiota dynamics following B. subtilis formulation challenge: an in vivo study in mice

Abstract

Background Modulating the microbiota is a leading-edge strategy for the restoration and maintenance of a healthy, balanced environment. The use of health-promoting bacteria has demonstrated some potential benefits as an alternative for skin microbiota intervention. Here, we investigate the manipulation of mice skin microbiota using B. subtilis incorporated into a supportive Pluronic F-127 hydrogel formulation. The formula plays an important role in delivering the bacteria to the desired action site. Results The B. subtilis challenge induced a shift in the composition and abundance of the skin microbiota. Containment of B. subtilis in the Pluronic F-127 hydrogel accelerated bacterial modulation compared with free B. subtilis. The abundance of both Staphylococcus and Corynebacterium spp. was altered as a result of the live bacterial intervention: the abundance of Corynebacterium increased while that of Staphylococcus decreased. Four days after last application of the B. subtilis formulation, B. subtilis counts returned to its initial level. Conclusions B. subtilis intervention can induce a shift in the skin microbiota, influencing the abundance of commensal, beneficial, and pathogenic bacteria. Containment of B. subtilis in Pluronic hydrogel accelerates the microbial alteration, probably by facilitating bacterial attachment and supporting continuous growth. Our results reveal the ability of B. subtilis in Pluronic to modulate the skin microbiota composition, suggesting that the formulation holds therapeutic potential for skin disease treatment.

Feasibility of engineered Bacillus subtilis for use as a microbiome‐based topical drug delivery platform

“…In agreement with this observation, other work analyzing the shift in mouse ear microbiota composition during and after B. subtilis administration found that there were shifts in the microbiota composition during administration of the bacteria, but the microbiota composition was similar to that of the untreated control group within a week after stopping administration of bacteria. 25 Starting with equal numbers of the representative skin microbiome species in this model, the relative steady state percentages predicted by the computational model qualitatively matched relative percentages of their genera identified from swabs of human forearm skin. 26 The computational model also predicted that a species with doubling time and carbon source utilization characteristics representative of B. subtilis could survive within an established community representing the skin microbiome for a little over half a day.…”

Injectable thermo-sensitive hydrogel enhances anti-tumor potency of engineered Lactococcus lactis by activating dendritic cells and effective memory T cells

“…As FDA-approved polymer, the construction and biocompatibility of poloxamer 407 are proved in our study, in line with previous reports [ 33 ]. P407 were employed as carrier of microbiota-modulating agent like bacillus for skin infection treatment mainly due to its lower critical solution temperature, since it allows bacteria to grow inside the formula, prolong the retention of bacteria in the injection location without compromising bacteria's ability to produce and secret [ 46 ]. Therefore, we speculate P407 hydrogel could also prolong the preservation of FOLactis and be beneficial for secreting of fusion protein containing Flt3L and OX40L, which has been proved in follow-up experiment.…”

Hydrogels as promising platforms for engineered living bacteria-mediated therapeutic systems

“…As an example, alginate-derived hydrogels ionically crosslinked by Ca 2+ have been widely employed to construct living bacterial delivery systems due to their excellent cell compatibility and gentle gelation behaviors [ [47] , [48] , [49] , [50] ]. Thermogelling hydrogels have also been used in previous works to deliver living bacteria to their convenience during both the preparation of the bacteria-encapsulating hydrogel precursor solutions and in vivo administration [ 41 , [51] , [52] , [53] ]. However, the relatively high critical concentration and low mechanical strength of physical hydrogels are unfavorable for the exchange of substances and long-term bacterial survival during the treatment process.…”

“…Furthermore, the tunable mechanical properties and penetrability of this living bacterial agent increased its potential for antifungal applications. Moreover, their subsequent study revealed that B. subtilis in Pluronic F-127 has the capability to modulate the composition of the skin microbiota, which is beneficial for skin disease treatment [ 52 ].…”