Colorectal carcinoma (CRC) is one of the most common causes of cancer-related mortality. Short-chain fatty acids secreted by dietary propionibacteria from the intestine, such as acetate, induce apoptosis in CRC cells and may therefore be relevant in CRC prevention and therapy. We previously reported that acetic acid-induced apoptosis in Saccharomyces cerevisiae cells involves partial vacuole permeabilization and release of Pep4p, the yeast cathepsin D (CatD), which has a protective role in this process. In cancer cells, lysosomes have emerged as key players in apoptosis through selective lysosomal membrane permeabilization (LMP) and release of cathepsins. However, the role of CatD in CRC survival is controversial and has not been assessed in response to acetate. We aimed to ascertain whether LMP and CatD are involved in acetate-induced apoptosis in CRC cells. We showed that acetate per se inhibits proliferation and induces apoptosis. More importantly, we uncovered that acetate triggers LMP and CatD release to the cytosol. Pepstatin A (a CatD inhibitor) but not E64d (a cathepsin B and L inhibitor) increased acetate-induced apoptosis of CRC cells, suggesting that CatD has a protective role in this process. Our data indicate that acetate induces LMP and subsequent release of CatD in CRC cells undergoing apoptosis, and suggest exploiting novel strategies using acetate as a prevention/therapeutic agent in CRC, through simultaneous treatment with CatD inhibitors.

: Colorectal Cancer (CRC) is a major cause of cancer-related death worldwide. CRC increased risk has been associated with alterations in the intestinal microbiota, with decreased production of Short Chain Fatty Acids (SCFAs). SCFAs produced in the human colon are the major products of bacterial fermentation of undigested dietary fiber and starch. While colonocytes use the three major SCFAs, namely acetate, propionate and butyrate, as energy sources, transformed CRC cells primarily undergo aerobic glycolysis. Compared to normal colonocytes, CRC cells exhibit increased sensitivity to SCFAs, thus indicating they play an important role in cell homeostasis. Manipulation of SCFA levels in the intestine, through changes in microbiota, has therefore emerged as a potential preventive/therapeutic strategy for CRC. Interest in understanding SCFAs mechanism of action in CRC cells has increased in the last years. Several SCFA transporters like SMCT-1, MCT-1 and aquaporins have been identified as the main transmembrane transporters in intestinal cells. Recently, it was shown that acetate promotes plasma membrane re-localization of MCT-1 and triggers changes in the glucose metabolism. SCFAs induce apoptotic cell death in CRC cells, and further mechanisms have been discovered, including the involvement of lysosomal membrane permeabilization, associated with mitochondria dysfunction and degradation. : In this review, we will discuss the current knowledge on the transport of SCFAs by CRC cells and their effects on CRC metabolism and survival. The impact of increasing SCFA production by manipulation of colon microbiota on the prevention/therapy of CRC will also be addressed.

Acetate is a short-chain fatty acid secreted by Propionibacteria from the human intestine, known to induce mitochondrial apoptotic death in colorectal cancer (CRC) cells. We previously established that acetate also induces lysosome membrane permeabilization in CRC cells, associated with release of the lysosomal protease cathepsin D (CatD), which has a well-established role in the mitochondrial apoptotic cascade. Unexpectedly, we showed that CatD has an antiapoptotic role in this process, as pepstatin A (a CatD inhibitor) increased acetate-induced apoptosis. These results mimicked our previous data in the yeast system showing that acetic acid activates a mitochondria-dependent apoptosis process associated with vacuolar membrane permeabilization and release of the vacuolar protease Pep4p, ortholog of mammalian CatD. Indeed, this protease was required for cell survival in a manner dependent on its catalytic activity and for efficient mitochondrial degradation independently of autophagy. In this study, we therefore assessed the role of CatD in acetate-induced mitochondrial alterations. We found that, similar to acetic acid in yeast, acetate-induced apoptosis is not associated with autophagy induction in CRC cells. Moreover, inhibition of CatD with small interfering RNA or pepstatin A enhanced apoptosis associated with higher mitochondrial dysfunction and increased mitochondrial mass. This effect seems to be specific, as inhibition of CatB and CatL with E-64d had no effect, nor were these proteases significantly released to the cytosol during acetate-induced apoptosis. Using yeast cells, we further show that the role of Pep4p in mitochondrial degradation depends on its protease activity and is complemented by CatD, indicating that this mechanism is conserved. In summary, the clues provided by the yeast model unveiled a novel CatD function in the degradation of damaged mitochondria when autophagy is impaired, which protects CRC cells from acetate-induced apoptosis. CatD inhibitors could therefore enhance acetate-mediated cancer cell death, presenting a novel strategy for prevention or therapy of CRC.

In order to support the elevated market demand for the development of textiles with specific benefits for a healthy and safe lifestyle, several bioactive textiles with defined properties, including antimicrobial, antioxidant, anti-inflammatory, anti-odor, and anti-repellent, anti-ultraviolet (UV) radiation, have been proposed. Antimicrobial textiles, particularly, have received special interest considering the search for smart, protective textiles that also impact health and well-being. Although the incorporation of antimicrobials into textile material has been well succeeded, the addition of such components in textile clothing can influence the balance of the skin microbiota of the wearer. While most antimicrobial textiles have demonstrated good biocompatibility and antimicrobial performance against bacteria, fungi, and viruses, some problems such as textile biodegradation, odor, and dissemination of unwanted microorganisms might arise. However, little is known about the impact of such antimicrobial textile-products on human skin microbiota. To address this issue, the present review, for the first time, gives an overview about the main effects of antimicrobial textiles, i.e., antibacterial, antifungal, and antiviral, on skin microbiota while driving future investigation to elucidate their putative clinical relevance and possible applications according to their impact on skin microbiota. This knowledge may open doors for the development of more microbiota friendly textiles or antimicrobial textile-products able to target specific populations of the skin microbiota aiming to alleviate skin disorders, malodor, and allergies by avoiding the growth and spread of pathogenic microorganisms.

Oral diseases affect over three billion people worldwide, making it one of the most common infections. Recent studies show that one approach to reducing the risk of chronic infections, such as caries, gingivitis, periodontitis, and halitosis, is to control the ecology of the oral microbiome instead of completely removing both the harmful and beneficial microorganisms. This is based on the knowledge that oral diseases are not caused by a single pathogen but rather by a shift in the homeostasis of the entire microbiota, a process known as dysbiosis. Consequently, it is of the utmost importance to implement strategies that are able to prevent and control oral dysbiosis to avoid serious complications, including heart, lung, and other systemic diseases. Conventional treatments include the use of antibiotics, which further disrupt the equilibrium in the oral microbiota, together with the mechanical removal of the decayed cavity area following its formation. Therefore, it is imperative to implement alternative strategies with the potential to overcome the disadvantages of the current therapy, namely, the use of broad-spectrum antibiotics. In this sense, probiotics and postbiotics have received particular attention since they can modulate the oral microbiota and decrease the dysbiotic rate in the oral cavity. However, their mechanisms of action need to be addressed to clarify and drive their possible applications as preventive strategies. In this sense, this review provides an overview of the potential of probiotics and postbiotics, focusing on their antimicrobial and antibiofilm activities as well as their ability to modulate the inflammatory response. Finally, it also showcases the main advantages and disadvantages of orodispersible films—a promising delivery mechanism for both probiotics and postbiotics to target oral dysbiosis.

The bone microenvironment is characterized by an intricate interplay between cellular and noncellular components, which controls bone remodeling and repair. Its highly hierarchical architecture and dynamic composition provide a unique microenvironment as source of inspiration for the design of a wide variety of bone tissue engineering strategies. To overcome current limitations associated with the gold standard for the treatment of bone fractures and defects, bioengineered bone microenvironments have the potential to orchestrate the process of bone regeneration in a self-regulated manner. However, successful approaches require a strategic combination of osteogenic, vasculogenic, and immunomodulatory factors through a synergic coordination between bone cells, bone-forming factors, and biomaterials. Herein, we provide an overview of (i) current three-dimensional strategies that mimic the bone microenvironment and (ii) potential applications of bioengineered microenvironments. These strategies range from simple to highly complex, aiming to recreate the architecture and spatial organization of cell–cell, cell-matrix, and cell-soluble factor interactions resembling the in vivo microenvironment. While several bone microenvironment-mimicking strategies with biophysical and biochemical cues have been proposed, approaches that exploit the ability of the cells to self-organize into microenvironments with a high regenerative capacity should become a top priority in the design of strategies toward bone regeneration. These miniaturized bone platforms may recapitulate key characteristics of the bone regenerative process and hold great promise to provide new treatment concepts for the next generation of bone implants.