Search Results (23)

This study evaluated the impact of a proprietary blend of fruit and vegetable fibers rich in naturally occurring bound polyphenols (commercially marketed as NatureKnit^TM), compared to purified fibers (inulin and psyllium), on the human gut microbiome using the validated M-SHIME^® gastrointestinal model. A short-term single-stage colonic M-SHIME^® experiment (with fecal inoculum from three healthy human donors) was used to evaluate the test products compared to a negative control. Samples were assessed for pH, gas pressure, short-chain fatty acid (SCFA) production, lactate, and ammonium from 0 h to 48 h. Microbial community composition was assessed at 0 h (negative control only), 24 h, and 48 h (lumen) or 48 h (mucosal). All test products were fermented well in the colon as demonstrated by decreases in pH and increases in gas pressure over time; these changes occurred faster with the purified fibers, whereas NatureKnit™ demonstrated slow, steady changes, potentially indicating a gentler fermentation process. SCFA production significantly increased over the course of the 48 h experiment with all test products versus negative control. SCFA production was significantly greater with NatureKnit™ versus the purified fibers. Shifts in the microbial community composition were observed with all test products versus negative control. At the conclusion of the 48 h experiment, the absolute bacterial abundance and the richness of observed bacterial taxa in the lumen compartment was significantly greater with NatureKnit™ compared with inulin, psyllium, and negative control. Overall, NatureKnit™ demonstrated greater or similar prebiotic effects on study measures compared with established prebiotic fibers. Full article

Blackcurrant is an anthocyanin-rich berry with proven antioxidant and photoprotective activity and emerging prebiotic potential, widely applied in cosmetic products. Hereby, highly efficient enzyme-assisted extraction of blackcurrant polyphenols was performed, giving extract with very high antioxidant activity. Obtained extract was characterized in terms of anthocyanin composition, incorporated into three different cosmetic formulations and subjected to Franz cell diffusion study. Experimental values obtained using cellulose acetate membrane for all four dominant anthocyanins (delphinidin 3-glucoside, delphinidin 3-rutinoside, cyanidin 3-glucoside and cyanidin 3-rutinoside) were successfully fitted with the Korsmeyer–Peppas diffusion model. Calculated effective diffusion coefficients were higher for hydrogel compared to oil-in-water cream gel and oil-in-water emulsion, whereas the highest value was determined for cyanidin 3-rutinoside. On the other hand, after a 72 h long experiment with transdermal skin diffusion model (Strat-M^® membrane), no anthocyanins were detected in the receptor fluid, and only 0.5% of the initial quantity from the donor compartment was extracted from the membrane itself after experiment with hydrogel. Present study revealed that hydrogel is a suitable carrier system for the topical delivery of blackcurrant anthocyanins, while dermal and transdermal delivery of these molecules is very limited, which implies its applicability for treatments targeting skin surface (i.e., prebiotic, photoprotective). Full article

We present a simple mathematical model that captures the evolutionary capabilities of a prebiotic compartment or protocell. In the model, the protocell contains an autocatalytic set whose chemical dynamics is coupled to the growth–division dynamics of the compartment. Bistability in the dynamics of the autocatalytic set results in a protocell that can exist with two distinct growth rates. Stochasticity in chemical reactions plays the role of mutations and causes transitions from one growth regime to another. We show that the system exhibits ‘natural selection’, where a ‘mutant’ protocell in which the autocatalytic set is active arises by chance in a population of inactive protocells, and then takes over the population because of its higher growth rate or ‘fitness’. The work integrates three levels of dynamics: intracellular chemical, single protocell, and population (or ecosystem) of protocells. Full article

The chemical evolution of biomolecules was clearly affected by the overall extreme environmental conditions found on Early Earth. Periodic temperature changes inside the Earth’s crust may have played a role in the emergence and survival of functional peptides embedded in vesicular compartments. In this study, all-atom molecular dynamic (MD) simulations were used to elucidate the effect of temperature on the properties of functionalized vesicle membranes. A plausible prebiotic system was selected, constituted by a model membrane bilayer from an equimolar mixture of long-chain fatty acids and fatty amines, and an octapeptide, KSPFPFAA, previously identified as an optimized functional peptide in an evolution experiment. This peptide tends to form the largest spontaneous aggregates at higher temperatures, thereby enhancing the pore-formation process and the eventual transfer of essential molecules in a prebiotic scenario. The analyses also suggest that peptide–amphiphile interactions affect the structural properties of the membrane, with a significant increase in the degree of interdigitation at the lowest temperatures under study. Full article

The origin of life possibly required processes in confined systems that facilitated simple chemical reactions and other more complex reactions impossible to achieve under the condition of infinite dilution. In this context, the self-assembly of micelles or vesicles derived from prebiotic amphiphilic molecules is a cornerstone in the chemical evolution pathway. A prime example of these building blocks is decanoic acid, a short-chain fatty acid capable of self-assembling under ambient conditions. This study explored a simplified system made of decanoic acids under temperatures ranging from 0 °C to 110 °C to replicate prebiotic conditions. The study revealed the first point of aggregation of decanoic acid into vesicles and examined the insertion of a prebiotic-like peptide in a primitive bilayer. The information gathered from this research provides critical insights into molecule interactions with primitive membranes, allowing us to understand the first nanometric compartments needed to trigger further reactions that were essential for the origin of life. Full article

Metal ions strongly affect the self-assembly and stability of membranes composed of prebiotically relevant amphiphiles (protoamphiphiles). Therefore, evaluating the behavior of such amphiphiles in the presence of ions is a crucial step towards assessing their potential as model protocell compartments. We have recently reported vesicle formation by N-acyl amino acids (NAAs), an interesting class of protoamphiphiles containing an amino acid linked to a fatty acid via an amide linkage. Herein, we explore the effect of ions on the self-assembly and stability of model N-oleoyl glycine (NOG)-based membranes. Microscopic analysis showed that the blended membranes of NOG and Glycerol 1-monooleate (GMO) were more stable than pure NOG vesicles, both in the presence of monovalent and divalent cations, with the overall vesicle stability being 100-fold higher in the presence of a monovalent cation. Furthermore, both pure NOG and NOG + GMO mixed systems were able to self-assemble into vesicles in natural water samples containing multiple ions that were collected from active hot spring sites. Our study reveals that several aspects of the metal ion stability of NAA-based membranes are comparable to those of fatty acid-based systems, while also confirming the robustness of compositionally heterogeneous membranes towards high metal ion concentrations. Pertinently, the vesicle formation by NAA-based systems in terrestrial hot spring samples indicates the conduciveness of these low ionic strength freshwater systems for facilitating prebiotic membrane-assembly processes. This further highlights their potential to serve as a plausible niche for the emergence of cellular life on the early Earth. Full article

GoodBiome™ Foods is a collection of foods infused with prebiotics, including inulin and xylooligosaccharides, and the probiotic Bacillus subtilis HU58. The effects of repeated intake of three predigested GoodBiome™ Foods products and one comparator product on microbial community activity and composition were assessed using the mucosal simulator of the human intestinal microbial system (M-SHIME^®) platform with proximal colon (PC) and distal colon (DC) compartments and conducted under healthy gut conditions. Treatment with all test products increased short-chain fatty acid (SCFA) production (acetate, propionate, and butyrate) versus the control period in both the PC and DC. The highest increases were seen with the GoodBiome™ Foods products. Ammonium and branched SCFA levels were also increased (versus the control period) in both compartments. Treatment with all test products enhanced the Simpson diversity index (versus the control period), reaching significance for all test products in the PC (p < 0.05). Treatment with all test products resulted in changes in the microbial community composition. The relative abundance increased for Proteobacteria and decreased for Actinobacteria in the PC and DC. Repeated intake of GoodBiome™ Food products increased SCFA production and microbial diversity in an M-SHIME^® model of the human intestinal microbiome. Full article

The human gut microbiota has been linked to the health status of the host. Modulation of human gut microbiota through pro- and prebiotic interventions has yielded promising results; however, the effect of novel prebiotics, such as chitin–glucan, on gut microbiota–host interplay is still not fully characterized. We assessed the effect of chitin–glucan (CG) and chitin–glucan plus Bifidobacterium breve (CGB) on human gut microbiota from the luminal and mucosal environments in vitro. Further, we tested the effect of filter-sterilized fecal supernatants from CG and CGB fermentation for protective effects on inflammation-induced barrier disruption and cytokine production using a co-culture of enterocytes and macrophage-like cells. Overall, CG and CGB promote health-beneficial short-chain fatty acid production and shift human gut microbiota composition, with a consistent effect increasing Roseburia spp. and butyrate producing-bacteria. In two of three donors, CG and CGB also stimulated Faecalibacterium prausniitzi. Specific colonization of B. breve was observed in the lumen and mucosal compartment; however, no synergy was detected for different endpoints when comparing CGB and CG. Both treatments included a significant improvement of inflammation-disrupted epithelial barrier and shifts on cytokine production, especially by consistent increase in the immunomodulatory cytokines IL10 and IL6. Full article

Compartmentalisation by bioenergetic membranes is a universal feature of life. The eventual compartmentalisation of prebiotic systems is therefore often argued to comprise a key step during the origin of life. Compartments may have been active participants in prebiotic chemistry, concentrating and spatially organising key reactants. However, most prebiotically plausible compartments are leaky or unstable, limiting their utility. Here, we develop a new hypothesis for an origin of life environment that capitalises upon, and mitigates the limitations of, prebiotic compartments: multi-compartmentalised layers in the near surface environment—a ’scum’. Scum-type environments benefit from many of the same ensemble-based advantages as microbial biofilms. In particular, scum layers mediate diffusion with the wider environments, favouring preservation and sharing of early informational molecules, along with the selective concentration of compatible prebiotic compounds. Biofilms are among the earliest traces imprinted by life in the rock record: we contend that prebiotic equivalents of these environments deserve future experimental investigation. Full article

Bovine milk oligosaccharides (BMO) share structural similarity to selected human milk oligosaccharides, which are natural prebiotics for infants. Thus, there is a potential in including BMOs as a prebiotic in infant formula. To examine the in vivo effect of BMO-supplementation on the infant gut microbiota, a BMO-rich diet (2% w/w) was fed to gnotobiotic mice (n = 11) inoculated with an infant type co-culture and compared with gnotobiotic mice receiving a control diet (n = 9). Nuclear magnetic resonance metabolomics in combination with high-throughput 16S rRNA gene amplicon sequencing was used to compare metabolic activity and microbiota composition in different compartments of the lower gastrointestinal tract. BMO components were detected in cecum and colon contents, revealing that BMO was available for the gut bacteria. The gut microbiota was dominated by Enterobacteriaceae and minor abundance of Lactobacilliaceae, while colonization of Bifidobacteriaceae did not succeed. Apart from a lower E. coli population in cecum content and lower formate (in colon) and succinate (in colon and cecum) concentrations, BMO supplementation did not result in significant changes in microbiota composition nor metabolic activity. The present study corroborates the importance of the presence of bifidobacteria for obtaining microbial-derived effects of milk oligosaccharides in the gastrointestinal tract. Full article

Numerous studies have indicated that the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD) is strictly associated with the accumulation of toxic metabolites in blood and other metabolic compartments. This accumulation was suggested to be related to enhanced generation of toxins from the dysbiotic microbiome accompanied by their reduced elimination by impaired kidneys. Intestinal microbiota play a key role in the accumulation of uremic toxins due to the fact that numerous uremic solutes are generated in the process of protein fermentation by colonic microbiota. Some disease states, including CKD, are associated with the presence of dysbiosis, which can be defined as an “imbalanced intestinal microbial community with quantitative and qualitative changes in the composition and metabolic activities of the gut microbiota”. The results of studies have confirmed the altered composition and functions of gut microbial community in chronic kidney disease. In the course of CKD protein-bound uremic toxins, including indoxyl sulfate, p-cresyl glucuronide, p-cresyl sulfate and indole-3-acetic acid are progressively accumulated. The presence of chronic kidney disease may be accompanied by the development of intestinal inflammation and epithelial barrier impairment leading to hastened systemic translocation of bacterial-derived uremic toxins and consequent oxidative stress injury to the kidney, cardiovascular and endocrine systems. These findings offer new therapeutic possibilities for the management of uremia, inflammation and kidney disease progression and the prevention of adverse outcomes in CKD patients. It seems that dietary interventions comprising prebiotics, probiotics, and synbiotics could pose a promising strategy in the management of uremic toxins in CKD. Full article

Liquid–liquid phase separation (LLPS) phenomena are ubiquitous in biological systems, as various cellular LLPS structures control important biological processes. Due to their ease of in vitro assembly into membraneless compartments and their presence within modern cells, LLPS systems have been postulated to be one potential form that the first cells on Earth took on. Recently, liquid crystal (LC)-coacervate droplets assembled from aqueous solutions of short double-stranded DNA (s-dsDNA) and poly-L-lysine (PLL) have been reported. Such LC-coacervates conjugate the advantages of an associative LLPS with the relevant long-range ordering and fluidity properties typical of LC, which reflect and propagate the physico-chemical properties of their molecular constituents. Here, we investigate the structure, assembly, and function of DNA LC-coacervates in the context of prebiotic molecular evolution and the emergence of functional protocells on early Earth. We observe through polarization microscopy that LC-coacervate systems can be dynamically assembled and disassembled based on prebiotically available environmental factors including temperature, salinity, and dehydration/rehydration cycles. Based on these observations, we discuss how LC-coacervates can in principle provide selective pressures effecting and sustaining chemical evolution within partially ordered compartments. Finally, we speculate about the potential for LC-coacervates to perform various biologically relevant properties, such as segregation and concentration of biomolecules, catalysis, and scaffolding, potentially providing additional structural complexity, such as linearization of nucleic acids and peptides within the LC ordered matrix, that could have promoted more efficient polymerization. While there are still a number of remaining open questions regarding coacervates, as protocell models, including how modern biologies acquired such membraneless organelles, further elucidation of the structure and function of different LLPS systems in the context of origins of life and prebiotic chemistry could provide new insights for understanding new pathways of molecular evolution possibly leading to the emergence of the first cells on Earth. Full article

Reconstitution of life-like properties in artificial cells is a current research frontier in synthetic biology. Mimicking metabolism, growth, and sensing are active areas of investigation; however, achieving motility and directional taxis are also challenging in the context of artificial cells. To tackle this problem, recent progress has been made that leverages the tools of active matter physics in synthetic biology. This review surveys the most significant achievements in designing motile cell-like compartments. In this context, strategies for self-propulsion are summarized, including, compartmentalization of catalytically active particles, phoretic propulsion of vesicles and emulsion droplet motion driven by Marangoni flows. This work showcases how the realization of motile protocells may impact biomedical engineering while also aiming at answering fundamental questions in locomotion of prebiotic cells. Full article

The loss of antibiotics as a tool to improve feed efficiency in poultry production has increased the urgency to understand how the microbiota interacts with animals to impact productivity and health. Modulating and harnessing microbiota-host interactions is a promising way to promote poultry health and production efficiencies without antibiotics. In poultry, the microbiome is influenced by many host and external factors including host species, age, gut compartment, diet, and environmental exposure to microbes. Because so many factors contribute to the microbiota composition, specific knowledge is needed to predict how the microbiome will respond to interventions. The effects of antibiotics on microbiomes have been well documented, with different classes of antibiotics having distinctive, specific outcomes on bacterial functions and membership. Non-antibiotic interventions, such as probiotics and prebiotics, target specific bacterial taxa or function to enhance beneficial properties of microbes in the gut. Beneficial bacteria provide a benefit by displacing pathogens and/or producing metabolites (e.g., short chain fatty acids or tryptophan metabolites) that promote poultry health by improving mucosal barrier function or immune function. Microbiota modulation has been used as a tool to reduce pathogen carriage, improve growth, and modulate the immune system. An increased understanding of how the microbiota interacts with animal hosts will improve microbiome intervention strategies to mitigate production losses without the need for antibiotics. Full article

Allergic diseases now affect over 30% of individuals in many communities, particularly young children, underscoring the need for effective prevention strategies in early life. These allergic conditions have been linked to environmental and lifestyle changes driving the dysfunction of three interdependent biological systems: microbiota, epithelial barrier and immune system. While this is multifactorial, dietary changes are of particular interest in the altered establishment and maturation of the microbiome, including the associated profile of metabolites that modulate immune development and barrier function. Prebiotics are non-digestible food ingredients that beneficially influence the health of the host by 1) acting as a fermentable substrate for some specific commensal host bacteria leading to the release of short-chain fatty acids in the gut intestinal tract influencing many molecular and cellular processes; 2) acting directly on several compartments and specifically on different patterns of cells (epithelial and immune cells). Nutrients with prebiotic properties are therefore of central interest in allergy prevention for their potential to promote a more tolerogenic environment through these multiple pathways. Both observational studies and experimental models lend further credence to this hypothesis. In this review, we describe both the mechanisms and the therapeutic evidence from preclinical and clinical studies exploring the role of prebiotics in allergy prevention. Full article