Editorial

Genetics and Environmental Interactions Shape the Intestinal Microbiome to Promote Inflammatory Bowel Disease Versus Mucosal Homeostasis

and study aims: Gastrointestinal microbiota are closely related to the pathogenesis of ulcerative colitis (UC). This study aimed at quantification of F. prausnitzii, Provetella, and Peptostreptococcus in UC and non-UC patients using Real-Time PCR and a new set of primers were also validated for this purpose.

In this study, the relative abundance of microbial populations between the UC and non-UC subjects were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). DNA extraction from biopsies and polymerase chain reaction (PCR) amplification of bacterial 16S rRNA gene-targeted species-specific primers was performed to detect the anaerobic bacterial species. The qRT-PCR was used to show the relative change in the bacterial populations of F. prausnitzii, Provetella, and Peptostreptococcus in the UC and non-UC subjects.

Our data for detection of the anaerobic intestinal flora showed Faecalibacterium prausnitzii, Provetella and Peptostreptococcus were the predominant microflora in the controls and showed significant differences (p = 0.002, 0.025 and 0.039, respectively). The qRT-PCR analyses of F. prausnitzii, Provetella and Peptostreptococcus were 8.69-, 9.38- and 5.77-higher, respectively, in the control group than in the UC group.

The results of this study showed decreased abundance of F. prausnitzii, Provetella and Peptostreptococcus in the intestine of UC patients in comparison to non-UC patients. Quantitative RT-PCR, as a progressive and sensitive method, could be useful for evaluation of bacterial populations in patients with inflammatory bowel diseases to attain appropriate therapeutic strategies.

Ulcerative colitis and Crohn’s disease are inflammatory bowel diseases (IBD) characterized primarily by increased permeability of the intestinal barrier, immunological dysregulation, inflammation, and/or dysbiosis. Current treatments use medications such as corticosteroids and aminosalicylates, and the relationship between their benefit and adverse effects is not always adequate for patients. Thus, natural alternatives for the treatment of IBD have been investigated, such as the use of algae and mushrooms. These natural products associated with plant life have shown promising effects in colitis models and in patients with IBD. In general, the modulating effects of the inflammatory response and the gut microbiota are associated with the presence of bioactive compounds in these foods, mainly sulfated polysaccharides in algae and β-glucans in mushrooms. So far, reestablishing the balance of inflammatory cytokines, reducing histological damage, and improving symptoms were the main findings of research that uses these natural products as an alternative therapy for IBD.

Although the strategy for administering antibodies orally for inflammatory bowel disease (IBD) treatment has been proposed, the rational design for efficient delivery system is still a challenge, restricted by poor drug loading and nonspecific distribution. In this study, we developed an inflammatory microenvironment-responsive nanocomplex (IFX_SS@HA or IFX_TK@HA) for oral administration of Infliximab (IFX) for IBD treatment using self-cross-linking technology, which was developed by reactive oxygen species–responsive cross-linkers and fabricated with hyaluronic acid. The nanocomplex is a “carrier-free” antibody backpack with a high drug loading (>90%), inflammation targeting, and bioresponsive controlled release. The results of preliminary in vivo studies indicated that the nanocomplex showed an extended retention time and caused an increased antibody accumulation in the inflamed intestinal tissues based on hyaluronic acid functionalization and responsive controlled release within the inflammation site, exhibiting great efficacy by reducing intestinal inflammation and systemic exposure. This study provided a rational design for an oral delivery system of antibodies, explored the design of the combination of vehicle and functionalization, and showed a strategy for the oral administration of antibodies in IBD treatment.

Inflammatory bowel disease (IBD) is a chronic and recurrent disease of the gastrointestinal tract, mainly including Crohn's disease (CD) and ulcerative colitis (UC). However, current approaches against IBD do not precisely deliver drugs to the inflammatory site, which leads to life-long medication and serious side effects that can adversely impact patients’ adherence. It is necessary to construct optimal drug delivery systems (DDSs) that can target drugs to the region of inflammation, thereby improve therapeutic efficacy and reduce side effects. With the burgeoning development of nanotechnology-based nanomedicines (NMs) and prodrug strategy, remarkable progresses in the treatment of IBD have been made in recent years. Herein, the latest advances are outlined at the intersection of IBD treatment and nanotherapeutics as well as prodrug therapy. First, the pathophysiological microenvironment of inflammatory sites of IBD is introduced in order to rationally design potential NMs and prodrugs. Second, the necessity of NMs for the IBD therapy is elaborated, and the representative nanotherapeutics via passive targeted and active targeted NMs developed to treat the IBD are overviewed. Furthermore, the emerging prodrug-based therapeutics are summarized, including 5-aminosalicylic acid-, amino acid-, and carbohydrate-conjugated prodrugs. Finally, the design considerations and perspectives of these NMs and prodrugs-driven IBD therapeutics in the clinical translation are spotlighted.

Inflammatory bowel disease (IBD) is a chronic intestinal disease with painful clinical manifestations and high risks of cancerization. With no curative therapy for IBD at present, the development of effective therapeutics is highly advocated. Drug delivery systems have been extensively studied to transmit therapeutics to inflamed colon sites through the enhanced permeability and retention (EPR) effect caused by the inflammation. However, the drug still could not achieve effective concentration value that merely utilized on EPR effect and display better therapeutic efficacy in the inflamed region because of nontargeted drug release. Substantial researches have shown that some specific receptors and cell adhesion molecules highly expresses on the surface of colonic endothelial and/or immune cells when IBD occurs, ligand-modified drug delivery systems targeting such receptors and cell adhesion molecules can specifically deliver drug into inflamed sites and obtain great curative effects. This review introduces the overexpressed receptors and cell adhesion molecules in inflamed colon sites and retrospects the drug delivery systems functionalized by related ligands. Finally, challenges and future directions in this field are presented to advance the development of the receptor-mediated targeted drug delivery systems for the therapy of IBD.

Impacts, traumas and strokes are spontaneously life-threatening, but chronic symptoms strangle patient every day. Colorectal tissue mechanics in such chronic situations not only regulates the physio-psychological well-being of the patient, but also confirms the level of comfort and post-operative clinical outcomes. Numerous uniaxial and multiaxial tensile experiments on healthy and affected samples have evidenced significant differences in tissue mechanical behavior and strong colorectal anisotropy across each layer in thickness direction and along the length. Furthermore, this study reviewed various forms of passive constitutive models for the highly fibrous colorectal tissue ranging from the simplest linearly elastic and the conventional isotropic hyperelastic to the most sophisticated second harmonic generation image based anisotropic mathematical formulation. Under large deformation, the isotropic description of tissue mechanics is unequivocally ineffective which demands a microstructural based tissue definition. Therefore, the information collected in this review paper would present the current state-of-the-art in colorectal biomechanics and profoundly serve as updated computational resources to develop a sophisticated characterization of colorectal tissues.