This study evaluated the effects of replacing zinc bacitracin with a symbiotic diet on the biochemical profile, liver development, and Clostridium perfringens presence in laying hens at 90 weeks of age. A total of 198 Dekalb–White hens were assigned to six experimental diets: MBM (corn, soybean meal, and meat and bone meal), BAC (MBM + 0.05% zinc bacitracin), and SIMC (MBM + 0.1% symbiotic), provided from day 1 to 90 weeks. Additional treatments, SIMR and SIMP, received symbiotics from weeks 6 and 17, re-spectively. At 90 weeks, blood and tissue samples were analyzed. Results showed that symbiotic-treated hens had 20% heavier livers (P < 0.01) and lower concentrations of uric acid, total proteins, AST, ALT, and LDH (P < 0.01) compared to BAC-treated birds. Phosphorus, triglycerides, and HDL levels were better in symbiotic groups. C. perfringens counts and antibiotic resistance (ampicillin, erythromycin, aminoglyco-sides, lincomycin, tetracycline, bacitracin) were significantly higher in BAC groups (P < 0.01). Symbiotic supplementation improved intestinal health, reduced pathogenic bacterial colonization, and enhanced liver function compared to continuous antibiotic use, especially when administered from early life stages.

Systemic inflammation plays a central role in many diseases and is, therefore, an important therapeutic target. In a scoping review, we assessed the evidence base for anti-inflammatory effects of pre-, pro- and synbiotics in children. Of 1254 clinical trials published in English in Ovid Medline and Cochrane Library PubMed from January 2003 through September 2022, 29 were included in the review. In 6 studies of healthy children (n=1552), one reported that fructo-oligosaccharides added to infant formula significantly reduced pro-inflammatory biomarkers and one study of a single strain probiotic reported both anti- and pro-inflammatory effects. No effects were seen in the remaining two single-strain and one multi-strain probiotic and one synbiotic study. In 23 studies of children with diseases (n=1550), prebiotics were tested in 3, single-strain in 16 and multi-strain probiotics in 6 and synbiotics in 2 studies. Significantly reduced inflammatory biomarkers were reported in 7/10 studies of atopic/allergic conditions, 3/5 studies of auto-immune diseases, 1/2 studies of preterm infants, 1 study of overweight/obesity, 2/2 studies of severe illness and 2/3 studies of other diseases. However, often only one or two of several biomarkers were improved, increased pro-inflammatory biomarkers occurred in 5 of these studies and a probiotic increased inflammatory biomarkers in a study of newborns with congenital heart disease. The evidence base for the effects of pre-, pro- and synbiotics on systemic inflammation in children is weak. Further research is needed to determine if anti-inflammatory effects depend on the specific pre-, pro- and synbiotic preparations, health status and biomarkers studied.

Xylooligosaccharides (XOS) are components of hemicellulose and can be found in wheat bran, and barley hulls. Structurally, XOS consist of two to six xylose residues linked by β-(1,4) bonds. This makes them susceptible to subsequent treatment by intestinal bacteria, but the concentration of XOS is too low to show any prebiotic effects. Some industrial wastes, including brewers’ spent grain (BSG) and wheat bran peels (WBP), represent a major source of xylan, from which XOS is produced to provide a prebiotic effect in populations of colonic commensal microbiota. WBPs and BSGs were treated by microwave and enzymatic hydrolysis. Using the designed microwave pretreated enzymatic hydrolysis, 5.4 g of dry XOS was produced from 50 g WBP powder and 3.6 g dry XOS was produced from 50 g BSG powder. A single microwave treatment on WBP and BSG before enzymatic hydrolysis and 0.25 g/100 g enzyme raw material ratio were determined to be optimal. Effective microwave-assisted enzymatic hydrolysis of WBP and BSG were investigated, and contribute to improving the effectiveness of xylanase on WBP and BSG. Microwave-assisted enzymatic hydrolysis with xylanase and purification, obtaining food-grade XOS, was demonstrated as a step toward industrial-scale production.

A model of the early RNA world is proposed. Nearly self-complementary sequences that could adopt double-stranded, smallhairpin-like (shRNA), structures would be selected for due to their greater hydrolytic stability. These would be phosphorylated attheir 5' ends. We suppose that dehydrating conditions arise (perhaps intermittently) in the early environment allowing amino acidsto condense with these RNA molecules. The resulting phosphate-amino acid anhydrides would play the role of early, charged,tRNAs. A crude genetic code could emerge owing to the greater resistance of some amino acid-shRNA pairings to hydrolysisrelative to others. Early on there is no division of labor between mRNAs and tRNAs; the same molecules perform both functions.But the first systems would have encoded little in the way of protein sequence information. Rather they would have served as catalysts for the random polymerization of amino acids. It is speculated that the selective advantage inhering in such systems lay intheir ability to supply raw materials for the formation of coacervates within which the various molecules essential to proto-lifecould be concentrated. This would greatly facilitate the necessary chemistries. The evolution of homochiral protein and RNA populations is discussed. An appealing feature of this model is its ability to explain the transition from phosphorylated amino acids to the 3' ester-linked aminoacyl-tRNAs employed by modern life.

This review considers the generation of relatively simple biomolecules, e.g., primary amino acids, resulting from the rapid collapse of bubbles in aqueous solutions containing various, low molar mass, gases. Some of the possible primary reactions occurring to produce the biomolecules are introduced and discussed. A brief discussion is included on the possible involvement of hydrodynamic cavitation, at the primordial seashore, as the initiating processes for the formation of the first organic molecules on prebiotic earth and the origins of life on Earth some 4 billion years ago.

Prebiotic dietary fiber supplements are commonly consumed to help meet fiber recommendations and improve gastrointestinal health by stimulating beneficial bacteria and the production of short-chain fatty acids (SCFAs), molecules beneficial to host health. The objective of this research project was to compare potential prebiotic effects and fermentability of five commonly consumed fibers using an in vitro fermentation system measuring changes in fecal microbiota, total gas production and formation of common SCFAs. Fecal donations were collected from three healthy volunteers. Materials analyzed included: pure beta-glucan, Oatwell (commercially available oat-bran containing 22% oat β-glucan), xylooligosaccharides (XOS), WholeFiber (dried chicory root containing inulin, pectin, and hemi/celluloses), and pure inulin. Oatwell had the highest production of propionate at 12 h (4.76 μmol/mL) compared to inulin, WholeFiber and XOS samples (p<0.03). Oatwell’s effect was similar to those of the pure beta-glucan samples, both samples promoted the highest mean propionate production at 24 h. XOS resulted in a significant increase in the genus Bifidobacterium after 24 h of fermentation (0 h: 0.67 OTUs; 24 h: 5.22 OTUs; p = 0.038). Inulin and WholeFiber increased the beneficial genus Collinsella, consistent with findings in clinical studies. All analyzed compounds were fermentable and promoted the formation of beneficial SCFAs.

Self-assembly is a spontaneous process through which macroscopic structures are formed from basic microscopic constituents (e.g. molecules or colloids). By contrast, the formation of large biological molecules inside the cell (such as proteins or nucleic acids) is a process more akin to self-organization than to self-assembly, as it requires a constant supply of external energy. Recent studies have tried to merge self-assembly with self-organization by analyzing the assembly of self-propelled (or active) colloid-like particles whose motion is driven by a permanent source of energy. Here we present evidence that points to the fact that self-propulsion considerably enhances the assembly of polymers: self-propelled molecules are found to assemble into polymer-like structures, the average length of which increases towards a maximum as the self-propulsion force increases. Beyond this maximum, the average polymer length decreases due to the competition between bonding energy and disruptive forces that result from collisions. The assembly of active molecules might have promoted the formation of large pre-biotic polymers that could be the precursors of the informational polymers we observe nowadays.

Cocoa bean shells (CBSs) represent the external layer of cocoa beans. The shells are removed during the winnowing after the pre-roasting, a processing step of chocolate production; in in the past they were considered a waste. CBSs possess many interesting nutritional characteristics in both macro and micronutrients. CBSs result very rich in dietary fiber and antioxidant compounds such as phenolic acids and flavan-3-ols. Soluble dietary fibers are potentially associated with fermentability and prebiotic activity on human gut microbiota instead antioxidants compounds have been linked with positive effects on human health. Based on these properties, the aim of this study was the valorization of CBSs thorough enzymatic treatments. The shells were treated both raw and defatted; three sets of carbohydrases have been used in order to destructure the fiber profile, potentially enhancing the potential prebiotic activity of CBSs. Cellulase, xylanase and pectinase were used to perform enzymatic treatments. After the enzymatic hydrolisis, both soluble and insoluble fibers fraction were quantified, in parallel with the total phenolic and the total flavonoid contents and the antioxidant activity. Moreover, the HPLC-PDA analysis was carried out for the main compounds of CBSs. The enzymatic treatmens allowed to obtain an enhancement in soluble fibers, for both defatted and raw CBSs, particularly using cellulase, xylanase and their combinations. Finally, a parallel preservation of the antioxidant capacity and the content of the main bioactive compounds after the treatments was observed. These results can be used to exploit the enzymatic treated CBSs to further industrial applications in the food and nutraceutical fields.

The aquaculture sector has become increasingly reliant on soybean meal (SBM) and soy-derived proteins, because of their large abundance, low price and favorable amino acid profile. However, for Atlantic salmon, a major aquaculture species, the inclusion of soybean meal, and soy protein concentrate (SPC) in certain combinations has adverse impacts on its gut health and welfare. This study evaluated two enhanced SBM targeting improved gut health for inclusion in freshwater phase salmon diets, enzyme pre-treatment (ETS) and addition of fructose oligosaccharide (USP), respectively in comparison to untreated soybean meal (US) and fish meal (FM). The impact on growth performance, gut microbiome, and behaviors relevant to welfare was investigated. Both enhancements of SBM were found to support comparable growth performance to FM. Both targeted treatments altered the gut microbiome community. Fish fed SBM showed a tendency for more reactive behavior compared to those fed the FM-based control. All fish had a similarly low response to elicited stress, although ETS fed fish responded more actively than those fed the US diet. SBM fed fish also had lower repeatability of behavior, which may have implications for welfare. Both enhancements provide a promising basis to optimize the application of this widely used protein source.

A general method is presented that permits enantiomers, originally present in a low enantiomeric excess (%ee1), to accumulate in a high %ee (%ee2) without a chiral source present. An equation was derived that demonstrates the final %ee2 of any unreacted chiral starting material will become higher when that starting material has reacted to generate an additional chiral center, hence forming two sets of diastereomeric enantiomeric products. Importantly, chiral amplification factor (multiples), %ee2/%ee1, depends on the yield of this reaction (p), which exhibits a nonlinear increase in amplification as p approaches 100%. This process is inevitable. It represents a possible route by which small initial %ee1 values of prebiotic molecules could have been raised to high %ee2 contents during the pre-evolution of life period on Earth, without the need for an added chiral source to be present. This predicted behavior was then experimentally verified in Pictet-Spengler reactions of L-tryptophane methyl ester (L-TME) samples present in low enantiomeric excess (%ee1) with biacetyl or oxaldehyde (model reactions) run to various yields. Each reaction generates stereoisomer products, and chiral amplification of the L-TME’s initial %ee1 values to higher %ee2 values occurs in the unreacted (recovered) L-TME. Repeated cycles of these reactions create very high L-TME %ee values. Self-cyclodimerization of low %ee1 L-amino acids with their D-enantiomers to generate L,L-, D,D- and L,D-cyclic products were computationally studied, leading to the same conclusion. Small %ee1 values are enhanced to larger %ee2 in the unreacted starting materials.

Ramsey’s economic theory of saving (RTS) estimates how much of its commodities a nation should save to safeguard the well-being of future generations. Since RTS retains many attractive qualities such as simplicity, strength, breadth and generality, here we ask if it would be useful to investigate biophysical issues. Specifically, we focus on a biological topic that lends itself as a backdrop for the study of the imbalance between intake and expenditure, i.e., the evaluation of the multicellular living organisms’ energetic requirements and constraints. Our problem is to find at each time the optimum distribution and the right balance of the cellular energy budget between consumption and storage: how much must a living organism spare to increase its chances of survival over long periods? Suggesting how to find the optimum allocation of the available energy between expenditure and saving at each time, RTS approaches to biological energy budgets may have a wide range of experimental applications, such as: a) optimization of the long-term survival chances of either immortalized cell cultures, or beneficial bacterial colonies and exogenous probiotic mixtures; b) eradication of detrimental biofilms, such as, e.g., heart valves’ Streptococcus colonies; c) novel anti-stress and anti-ageing strategies.

Consumption of prebiotic fibers to modulate the human gut microbiome is a promising strategy to positively impact health. Nevertheless, given the compositional complexity of the microbiome and its inter-individual variances, generalized recommendations on the source or amount of fiber supplements remain vague. This problem is further compounded by availability of tractable in vitro and in vivo models to validate certain fibers. We employed a gnotobiotic mouse model containing an a priori characterized 14-member synthetic human gut microbiome (SM) for their ability to metabolize a suit of fibers in vitro; the SM contains 14 different strains belonging to five distinct phyla. Since soluble purified fibers have been a common subject of studies, we specifically investigated the effects of concentrated raw fibers (CRFs)—containing fibers from pea, oat, psyllium, wheat and apple—on the compositional and functional alterations in the SM. We demonstrate that, compared to a fiber-free diet, CRF supplementation increased the abundance of fiber-degraders namely Eubacterium rectale, Roseburia intestinalis and Bacteroides ovatus and decreased the abundance of the mucin-degrader Akkermansia muciniphila. These results were corroborated by a general increase of bacterial fiber-degrading α-glucosidase enzyme activity. Overall, our results highlight the ability of CRFs to enhance the microbial fiber-degrading capacity.

The prevalence of type-2 diabetes mellitus (T2D) is increasing worldwide and there are no long-term preventive strategies to stop this growth. Emerging research shows that perturbations in the gut microbiome significantly contribute to the development of T2D, while microbiome modulators may be beneficial for T2D prevention. However, microbiome modulators that are effective, safe, affordable, and able to be integrated daily in the diet are not yet available. Based on our previous pro- and prebiotic studies, we developed a novel synbiotic yogurt comprised of human-origin probiotics and plant-based prebiotics and investigated its impact on diet- and streptozotocin-induced T2D in mice. We compared the effects of our synbiotic yogurt to those of a commercially-available yogurt (control yogurt). Interestingly, we found that feeding of this synbiotic yogurt significantly reduced the development of hyperglycemia (diabetes) in response to high-fat diet feeding and streptozotocin compared to milk-fed controls. Surprisingly, the control yogurt exacerbated diabetes progression. Synbiotic yogurt beneficially modulated the composition of gut microbiota compared to milk; conversely, the control yogurt negatively modulated the gut microbiota by significantly increasing the abundance of detrimental bacteria like Proteobacteria and Enterobacteriaceae. In addition, the synbiotic yogurt protected intact pancreatic islet morphology compared to the milk control, while the commercial yogurt demonstrated worse effects on pancreatic physiology. These results suggest that our newly developed synbiotic yogurt protects against diabetes in mice and can be used as a modality to prevent diabetes progression.

Understanding the importance of gut microbiota (GM) in non-alcoholic fatty liver disease (NAFLD) has raised the hope for therapeutic microbes. We have shown that high hepatic fat associated with low abundance of Faecalibacterium prausnitzii in humans and further, administration of F. prausnitzii prevented NAFLD in mice. Here, we aimed to target F. prausnitzii by prebiotic xylo-oligosaccharides (XOS) to treat NAFLD. First, the effect of XOS on F. prausnitzii growth was assessed in vitro. Then, XOS was supplemented or not with high (HFD) or low (LFD) fat-diet for 12-weeks in Wistar rats (n=10/group). XOS increased F. prausnitzii growth having only minor impact on the GM composition. When supplemented with HFD, XOS prevented hepatic steatosis. The underlying mechanisms involved enhanced hepatic β-oxidation and mitochondrial respiration. 1H-NMR analysis of caecal metabolites showed that compared to HFD, LFD group had healthier caecal short-chain fatty acid profile and the combination of HFD and XOS was associated with reduced caecal isovalerate and tyrosine, metabolites previously linked to NAFLD. Caecal branched-chain fatty acids associated positively and butyrate negatively with hepatic triglycerides. In conclusion, our study identifies F. prausnitzii as a possible target to treat NAFLD with XOS. The underlying preventive mechanisms involved improved hepatic oxidative metabolism.

On the primitive Earth, both L- and D-amino acids would have been present. However, only L-amino acids are essential blocks to construct proteins in modern life. To study the relative stability of homochiral and heterochiral peptides, a variety of computational methods were employed. 10 prebiotic amino acids (Gly, Ala, Asp, Glu, Ile, Leu, Pro, Ser, Thr, and Val) were previously determined by multiple previous meteorite, spark discharge, and hydrothermal vent studies. We focused on what had been reported as primary early Earth polypeptide analogs: 1ARK, 1PPT, 1ZFI, and 2LZE. Tripeptide composed of only Asp, Ser, and Val exemplified that different positions (i.e., N-terminus, C-terminus, and middle) made a difference in minimal folding energy of peptides, while the classification of amino acid (hydrophobic, acidic, or hydroxylic) did not show significant difference. Hierarchical cluster analysis for dipeptides with all possible combinations of the proposed 10 prebiotic amino acids and their D-amino acid substituted derivatives generated five clusters. Prebiotic polypeptides were built up to test the significance of molecular fluctuations, secondary structure occupancies, and folding energy differences based on these clusters. Most interestingly, among 129 residues, mutation sensitivity profiles presented that the ratio of more stable to less stable to equally stable D-amino acids was about 1:1:1. In conclusion, some combinations of a mixture of L- and D-amino acids can act as essential building blocks of life. Peptides with α-helices, long β-sheets, and long loops are usually less sensitive to D-amino acid replacements in comparison to short β-sheets.

I describe the non-equilibrium thermodynamics and the photochemical mechanisms which may have been involved in the dissipative synthesis, proliferation, and evolution of the fundamental molecules at the origin of life from simpler and more common precursor molecules such as HCN, H2O and CO2 under the impressed UVC photon flux of the Archean. The fundamental molecules absorb strongly in this UVC region and exhibit strong coupling between their electronic excited and ground states which endows them with efficient photon disipative capacity (broad wavelength absorption and rapid radiationless dexcitation) suggestive of dissipative structuring. The autocatalytic nature of the synthesized molecules in dissipating the same photochemical potential that directed their synthesis leads to their proliferation. The non-linearity in the photochemical and chemical reaction rates provides numerous stationary states which can be reached by amplification of a molecular concentration fluctuation near a bifurcation, promoting the system into states of generally higher photon disspative efficacy. An example is given of the UV photochemical dissipative structuring, proliferation, and evolution of molecules on route to the nucleobase adenine from the common precursor molecules HCN and H2O occurring within a fatty acid vesicle. The kinetic equations are resolved under different environmental conditions, providing a non-equilibrium thermodynamic analysis of the appearance of an early important molecule for the origin of life.

Gut microbiota play critical roles in development of obese-related metabolic diseases such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes, and insulin resistance, which highlighted the potential of gut microbiota-targeted therapies on these diseases. There are various ways that can manipulate gut microbiota including probiotics, prebiotics, synbiotics, antibiotics and some active components from herbal medicines. In this review, we first reviewed the main roles of gut microbiota in mediating the development of NAFLD, and the advances in gut microbiota-targeted therapies on NAFLD in both the experimental and clinical studies, as well as the conclusions on the prospect of gut microbiota-targeted therapies in the future.

The central dogma of molecular biology dictates that, with only a few exceptions, information proceeds from DNA to protein through an RNA intermediate. Examining the enigmatic steps from prebiotic to biological chemistry, we take another road suggesting that primordial peptides acted as template for the self-assembly of the first nucleic acids polymers. Arguing in favour of a sort of archaic “reverse translation” from proteins to RNA, our basic premise is a Hadean Hearth where key biomolecules such as amino acids, polypeptides, purines, pyrimidines, nucleosides and nucleotides were available under different prebiotically plausible conditions, including meteorites delivery, shallow ponds and hydrothermal vents scenarios. Supporting a protein-first scenario alternative to the RNA world hypothesis, we propose the primeval occurrence of short peptides termed “selective amino acid- and nucleotide-matching oligopeptides” (henceforward SANMAOs) that noncovalently bind at the same time the polymerized amino acids and the single nucleotides dispersed in the prebiotic milieu. We describe the chemical features of this hypothetical oligopeptide, its biological plausibility and its virtues from an evolutionary perspective. We provide a theoretical example of SANMAO’s selective pairing between amino acids and nucleosides, simulating a poly-Glycine peptide that acts as a template to build a purinic chain corresponding to the glycine’s extant triplet codon GGG. Further, we discuss how SANMAO might have endorsed the formation of low-fidelity RNA’s polymerized strains, well before the appearance of the accurate genetic material’s transmission ensured by the current translation apparatus.

Based on a new model of a possible origin of life, we establish an efficient and stable system undergoing structural reproduction, self-optimization and molecular evolution. This system is being formed under realistic conditions by the interaction of two cyclic processes, one of which offering vesicles as the structural environment, the other supplying peptides from a variety of amino acids as versatile building blocks. We demonstrate that structures growing in a combination of both cycles have the potential to support their own existence, to undergo chemical and structural evolution and to develop unpredicted functional properties. The key mechanism is the mutual stabilization of the peptides by the vesicles and of the vesicles by the peptides together with a constant production and selection of both. The development of the proposed system over time not only would represent one of the principles of life, but could also be a model for the formation of self-evolving structures ultimately leading to the first living cell. The experiment yields clear evidence on a vesicle-induced accumulation of membrane-interacting peptide which could be identified by liquid chromatography combined with high-resolution mass spectroscopy. We found that the selected peptide has an immediate effect on the vesicles, leading to i) reduced vesicle size, ii) increased vesicle membrane permeability, and iii) improved thermal vesicle stability.

A basic problem in all postulated pathways of prebiotic chemistry is the low concentration which generally is expected for interesting reactants in fluid environments. Even though compounds like nucleobases, sugars or peptides principally may form spontaneously under environmental conditions, they will always be rapidly diluted in an aqueous environment. In addition, any such reaction leads to side products which often exceed the desired compound and generally hamper the first steps of a subsequent molecular evolution. Therefore, a mechanism of selection and accumulation of relevant prebiotic compounds seems to be crucial for molecular evolution. A very efficient environment for selection and accumulation can be found in the fluid continuum circulating in tectonic fault zones. Vesicles which form spontaneously at a depth of approximately 1 km present a selective trap for amphiphilic molecules, especially for peptides composed of hydrophilic and hydrophobic amino acids in a suitable sequence. The accumulation effect is shown in a numeric simulation on a simplified model. Further, possible mechanisms of a molecular evolution in vesicle membranes are discussed. Altogether, the proposed scenario can be seen as an ideal environment for constant, undisturbed molecular evolution in and on cell-like compartments, the latter offering preferential starting conditions for a subsequent RNA world.

The gut, often referred to as the "second brain," has significant contributions in the maintaining of the good bacteria contribute enormous role such as digestion, produce essential vitamins, support the immune system, and protect against harmful bacteria. The beneficial flora including Akkermansia muciniphila, Adlercreutzia equolifasciens, Barnesiella, Christensenella minuta, and Oxalobacter formigenes, along with their derived bioactive metabolites emerged as a key player in maintaining host metabolic and immune health. Dietary choices such as blending of prebiotic, fermented, symbiotic, anti-inflammatory foods, and secondary metabolites from a wide variety of plants and fruits promotes the diversity, composition, and stability of beneficial intestinal microbes. The colourful plant foods rich in phytochemicals bioactive compounds such as carotenoids, flavonoids, polyphenols, alkaloids, anthocyanins, and capsaicin offer a wide array of unique properties such as analgesics, antioxidants, anti-inflammatory, antimicrobials effect and promoting the abundance of beneficial gut bacteria and their bioactive metabolites confer numerous health-promoting effects. Here, we present knowledge about most beneficial gut bacteria and their derived metabolites in terms of their sources and health benefits. Finally, we discuss best foods that skew towards promoting healthy intestinal microbes.

The emergence of Life has been a subject of intensive research for decades. Different approaches and different environmental “cradles” have been studied, from space to the deep-sea. Since the recent discovery of a natural electrical current through the deep-sea hydrothermal vent, a new energy source is considered for the transition from inorganic to organic. This energy source is used by modern microorganisms using a new trophic type, called electrotrophy. In this review, we draw the parallel between this metabolism and a new theory for the emergence of Life based on this electrical electron flow. Each step of the creation of Life is revised in the new light of this prebiotic electrochemical context, going from the evaluation of similar electrical current during the Hadean, the CO electroreduction into a prebiotic primordial soup, the production of proto-membranes, the energetic system inspired of the nitrate reduction, the proton gradient, and the transition to a planktonic proto-cell. Finally, this theory is compared to the two other theories in hydrothermal context, to assess its relevance to overcome the limitations of each one. Many critical factors that were limiting each theory can be overcome with the effect of the electrochemical reactions and the environmental changes produced.

Boron (B) is considered a prebiotic chemical element with a role in both the origin and evolution of life, as well as an essential micronutrient for plants, some bacteria, fungi, and algae. B has beneficial effects on the biological functions of humans and animals, such as reproduction, growth, calcium metabolism, bone formation, energy metabolism, immunity, brain function, and steroid hormones. In the future, naturally organic B (NOB) species may become promising novel prebiotic candidates. We included the most relevant works about NOB species, starting from our 30-year research experience. NOB-containing compounds have been shown essential for the symbiosis between different kingdoms. New insights into the essentiality of NOB species for healthy symbiosis between the human/animal host and the microbiota will determine the use of natural B-based nutraceuticals to target the colon (colonic foods). The mechanism of action (MoA) of NOB species is related to both the B signaling molecule [autoinducer-2–borate (AI-2B)], as well as the fortification of the colonic mucous gel layer with NOB species from the specific prebiotic boron-rich diet. Therefore, both microbiota and the mucous gel layer of the colon become the NOB species’ target. This paper reviews the evidence supporting the essentiality of the NOB species on the symbiosis between the microbiota and the human/animal host with the stated aim of highlighting the MoA and target of these species.

In many developing countries human health problems are solved using local plants. Knowledge of their chemical composition and biological activities can contribute to the creation of natural-based products usefully employed in human health. In this work, we analyzed Paederia grandidieri leaves extracted with diverse eco-compatible procedures and subjected to chemical, microbiological, and cellular compatibility assays. Fresh leaves of P. grandidieri were harvested in southern Madagascar, dried and powdered. Distilled water and ethanol at different temperatures and times were used for extraction. Polyphenol composition, antioxidant, antibacterial, prebiotic and cytotoxic properties of the extracts were analyzed. The aqueous extracts contained higher levels of flavan-3-ols and flavanones, while the hydro-alcoholic extracts were richer in flavonols and flavones. The aqueous extracts showed the highest total phenolic and total flavonoid contents, and antioxidant activity, but lower cytotoxicity with respect to the hydro-alcoholic extracts. None of the extracts had significant antibacterial effects against selected oral pathogens, but prebiotic effects against Streptococcus salivarius were detected. This study indicates that P. grandidieri possesses significant biological properties which make it a suitable candidate for the production of pro-health products for the oral cavity.

Despite substantial evidence supporting the efficacy of prebiotics for promoting host health and stress resilience, few experiments present evidence documenting the dynamic changes in microbial ecology and fecal microbial-modified metabolites across time. Furthermore, the literature reports a lack of reproducible effects of prebiotics on specific bacteria and bacterial-modified metabolites. The current experiments examined whether consumption of diets enriched in prebiotics (galactooligosaccharides, GOS and polydextrose, PDX) compared to control diet, would consistently impact the gut microbiome and microbial-modified bile acids across time and between two research sites. Male Sprague Dawley rats were fed control or prebiotic diets for several weeks, and their gut microbiome and metabolome were examined using 16S rRNA gene sequencing and untargeted LC-MS/MS analysis. Dietary prebiotics altered beta diversity, relative abundances of bacterial genera, and microbially modified bile acids across time. PICRUSt2 analyses identified four inferred functional metabolic pathways modified by prebiotic diet. Correlational network analyses between inferred metabolic pathways and microbial-modified bile acids revealed deoxycholic acid as a potential network hub. All these reported effects were consistent between the two research sites supporting the conclusion that dietary prebiotics robustly changed the gut microbial ecosystem. Consistent with our previous work demonstrating that GOS/PDX reduces the negative impacts of stressor exposure, we propose that ingesting a diet enriched in prebiotics facilitates the development of a health-promoting gut microbial ecosystem.

Phosphorylation reactions of glycerol were studied using different inorganic phosphates such as sodium phosphate, trimetaphosphate (a condensed phosphate), and struvite. The reactions were carried out in two non-aqueous solvents: formamide and a eutectic solvent consisting of choline chloride and glycerol in a ratio of 1:2.5. The glycerol reacted in formamide and in the eutectic solvent with phosphate to yield its phosphorylated derivatives in the presence of silicates such as quartz sand and kaolinite clay. The reactions were carried out by heating glycerol with a phosphate source at 85 °C for one week and were analyzed by 31P nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). The yield of the phosphorylated glycerol was improved by the presence of silicates, and reached 90% in some experiments. Our findings further support the proposal that non-aqueous solvents are advantageous for the prebiotic synthesis of biomolecules, and suggest that silicates may have aided in the formation of organophosphates on the prebiotic earth.

We hypothesize that the first ancestral "ante-cell" molecular structures, i.e., first RNAs and peptides which gradually transformed into real cells once the Earth had cooled sufficiently for organic molecules to appear there, have leaved traces in RNAs and genes of present cells. We propose a circular RNA which could have been one of these ancestral structures whose vestigial pentameric subsequences would mark the evolution from this key moment when the ante-cells have begun to join the living organisms. In particular, we propose that in present RNAs (ribosomal or messenger) playing an important role in the metabolism of current cells, we look for traces of the proposed primitive structure in the form of pentamers (or longer fragments) belonging to their nucleotide sequence. The result obtained can be summarized in the existence of a gradient of occurrence of such pentamers, with a high frequency for the most vital functions (protein synthesis, nucleic synthesis, cell respiration, etc.). This gradient is also visible between organisms, from the oldest (Archaea) to the most recent (Eukaryotes) in evolution of species.

This study investigated the effects of modified rice bran arabinoxylan compound (RBAC) as a dietary supplement on the gut microbiota of healthy adults. Ten volunteers supplemented their diet with 1g of RBAC for six weeks and 3g of RBAC for another six weeks, with a three-week washout period. Faecal samples were collected every 3 weeks over 21 weeks. Microbiota from faecal samples were profiled using 16S rRNA sequencing. Assessment of alpha and beta microbiota diversity was performed using the QIIME2 platform. The results revealed that alpha and beta diversity were not associated with the experimental phase, interventional period, RBAC dosage, or time. However, statistical significance of participant was detected in alpha (p&lt;0.002) and beta (weighted unifrac, p=0.001) diversity. Explanatory factors including age and diet were significantly associated with alpha (p&lt;0.05) and beta (p&lt;0.01) diversity. The individual beta diversity of six participants significantly changed (p&lt;0.05) during the interventional period. Seven participants showed statistically significant taxonomic changes (ANCOM W≥5). These results classified four participants as responders to RBAC supplementation, with a further two participants likely responders. In conclusion, the gut microbiome is highly individualised and modulated by RBAC as a dietary supplement, dependent on lifestyle and dietary intake

Evolutionary theory suggests that the origin, persistence, and evolution of biology is driven by the “natural selection” of characteristics improving the differential reproductive success of the organism in the given environment. The theory, however, lacks physical foundation, and, therefore, at best, can only be considered a heuristic narrative, of some utility for assimilating the biological and paleontological data at the level of the organism. On deeper analysis, it becomes apparent that this narrative is plagued with problems and paradoxes. Alternatively, non-equilibrium thermodynamic theory, derived from physical law, provides a physical foundation for describing material interaction with its environment at all scales. Here we describe a “natural thermodynamic selection” of characteristics of structures (or processes), based stochastically on increases in the global rate of dissipation of the prevailing solar spectrum. The different mechanisms of thermodynamic selection are delineated for the different biotic-abiotic levels, from the molecular level at the origin of life, up to the level of the present biosphere with non-linear coupling of biotic and abiotic processes. At the levels of the organism and the biosphere, the non-equilibrium thermodynamic description of evolution resembles, respectively, Darwinian and Gaia descriptions, although the underlying mechanisms and the objective function of selection are fundamentally very different.

It is proposed that the primary living cells (“probionts”) cannot emerge of organic substance simply by continuous chemical complication of prebiotic macromolecules and microsystems. The complication must be accompanied by the radical thermodynamic transformation (“jump”) of prebiotic microsystems that resulted in the acquired ability to extract free energy from the environment and export entropy. This transformation is called “the thermodynamic inversion” The inversion may occur by means of the efficient (intensified) response of the microsystems on the oscillations of physic-chemical parameters in hydrothermal environment. In this case the surplus available free energy within a microsystem, when combined with the informational modality, facilitates its conversion into a new microsystem—a living probiont. It is shown the schematic representation of an oscillating prebiotic microsystem that is transforming into a living probiont. A new kind of laboratory and computational experiments on prebiotic chemistry under oscillating conditions is offered to verify the inversion concept.

Geochemists disagree whether or not prebiotic chemistry has existed already during the Hadean Eon and whether the then terrestrial atmosphere has been strongly or weakly reduced. Here I argue that cellular life has existed already just after the end of the Hadean Eon and that terrestrial life has survived a number of cataclysms during the Earth's history. I argue that although organic molecules have been detected in meteorites that most organic molecules required for the formation of macromolecules must have been formed on Earth. Finally, I argue that the primitive terrestrial atmosphere during the Hadean Eon has been weakly reduced, so that amino acids and small nucleic acids could have been formed. I suggest that the first self-replicable macromolecules have been similar to viroids.

There is little doubt that life's origin followed from the known physical and chemical laws of Nature. The most general scientific framework incorporating the laws of Nature and applicable to most known processes to good approximation, is that of thermodynamics and its extensions to treat out-of-equilibrium phenomena. The event of the origin of life should therefore also be amenable to such an analysis. In this paper, I describe the non-equilibrium thermodynamic foundations of the origin of life for the non-expert. This ``Thermodynamic Dissipation Theory for the Origin of Life'' is founded on Classical Irreversible Thermodynamic theory developed by Lars Onsager, Ilya Prigogine, and coworkers.

Yogurt ice cream (YIC) containing Bifidobacterum longum subsp. longum TISTR 2195 (B. longum) with different fat contents (2 and 10% fat) and prebiotics (galacto-oligosaccharide, GOS and fructo-oligosaccharide, FOS) was investigated for its physicochemical properties, microstructure, and survival of B. longum during storage time and in a simulated gastrointestinal tract. Fat contents affected pH, fat particle size, hardness, melting rate, and solid-like characteristic of ice cream while FOS seemed to enhance the hardness and elasticity of YIC better than GOS due to less solubility and denser microstructure which exhibited more solid-like properties than YIC containing GOS. The interaction effect of fat content at 10% fat and FOS in YIC seemed to promote more sensorial acceptance than the ice cream containing 2% fat and GOS. The fat content, concentration of prebiotics, and type of prebiotics were attributed to the survival of B. longum in YIC. Moreover, the survival number of B. longum in YIC during storage for 180 days and in the simulated gastrointestinal tract was still in 106 CFU g-1, which is considered to benefit human health. Finally, probiotic YIC in this study could be used as a guide for functional ice cream manufacture future.

The origin of life was a cosmic event happened on primitive Earth. A critical problem to better understand the origins of life in Earth is to glimpse in which chemical scenarios the basic building blocks of biological molecules could be produced. Classic works in pre-biotic chemistry frequently considered early Earth as a homogeneous atmosphere constituted by chemical elements such as methane (CH₄), ammonia (NH₃), water (H₂O), hydrogen (H₂) and hydrogen sulfide (H₂S). Under that scenario, Stanley Miller was capable to produce amino acids and solved the question about the origin of proteins. Conversely, the origin of nucleic acids has tricked scientists for decades as nucleotides are complex though necessary molecules to allow the existence of life. Here we review possible chemical scenarios that allowed not only the formation of nucleotides but also other significant biomolecules. We aim to provide a theoretical solution for the origin of biomolecules at specific sites named “Prebiotic Chemical Refugia”. A prebiotic chemical refugium should therefore be understood as a geographic site in prebiotic Earth on which certain chemical elements were accumulated in higher proportion than expected, facilitating the production of basic biomolecules. Plus, this higher proportion should not be understood as static, but dynamic; once the physicochemical conditions of our planet changed periodically. This different concentration of elements, together with geochemical and astronomical changes along days, synodic months and years provided somewhat periodic changes in temperature, pressure, electromagnetic fields, and conditions of humidity; among other features. Recent and classic works suggesting most likely prebiotic refugia on which the main building blocks of biological molecules might be accumulated are reviewed and discussed.

Prebiotic organic synthesis reactions catalyzed by Earth-abundant metal sulfides are key processes for understanding the evolution of biochemistry from inorganic molecules, yet the catalytic functions of sulfides have remained poorly explored in the context of the origins of life. Past studies on prebiotic chemistry have mostly focused on a few types of metal sulfide catalysts, such as FeS or NiS, which form limited types of products with inferior activity and selectivity. To explore the potential of metal sulfides on catalyzing prebiotic chemical reactions, here, the chemical diversity (variations in chemical composition and phase structure) of 304 natural metal sulfide minerals in a mineralogy database was surveyed and approaches to rationally predict the catalytic functions of metal sulfides are discussed based on advanced theories and analytical tools of electrocatalysis such as proton-coupled electron transfer, structural comparisons between enzymes and minerals, and in-situ spectroscopy. To this end, we introduce a model of geo-electrochemistry driven prebiotic synthesis for chemical evolution, as it helps us to predict kinetics and selectivity of targeted prebiotic chemistry under “chemically messy conditions”. We expect that combining the data-mining of mineral databases with experimental methods and theories developed in the field of electrocatalysis will facilitate the prediction and verification of catalytic performance under a wide range of pH and Eh conditions, and aid in the rational screening of mineral catalysts involved in the origins of life.

Diamidophosphate has been identified as a possible prebiotic compound used in the precursor membranes of the first ‘life’. Compounds such as these will be helpful in developing novel biomimetic approaches in synthetic chemistry. Thermochemical data for this type of compounds are not available. Hess’ law and estimates from calorimetric measurements used by Wakefield in the 1970s for other amido phosphates have been used to estimate the thermochemical values for the diamido and monoamido-phosphoric acid. Enthalpy of formation at 298.15 ^oC is calculated as – 821.9 kJ/mol and the free energy of formation calculated as -813.5 kJ/mol for the diamidophosphoric acid. The calculated enthalpy of formation of monoamidic phosphoric acid is -1117.1 kJ/mol and its free energy of formation is - -1105 kJ/mol.

We have suggested that the abiogenisis of life around the beginning of the Archean may have been an example of microscopic dissipative structuring of UVC pigments (the fundamental molecules of life) under the prevailing surface UV solar spectrum. In a previous article in this series, we have describe the non-equilibrium thermodynamics and the photochemical mechanisms which may have been involved in the dissipative structuring of the purines adenine and hypoxanthine from the common precursor molecules of HCN and water under UVC light. In this article we extend our analysis to include the production of the other two important purines, guanine and xanthine, from these same precursors. The photochemical reactions are presumed to occur within a fatty acid vesicle floating on a hot ocean surface exposed to the prevailing UV light. Reaction-diffusion equations are resolved under different environmental conditions. Significant amounts of adenine (∼10−5 M) and guanine (∼10−6 M) are obtained within only a few months at 80 °C under plausible initial concentrations of HCN and cyanogen (a photochemical product of HCN).

Carrot juice and its associated beverage products are well-known healthy drinks all over the world. However, what effect carrot juice has on the human gut microbiota and how it is fermented by the intestinal microbes have not been studied. Here, using an in vitro model of anaerobic fermentation, we demonstrated that carrot juice could be fermented into lactate and acetate by the human gut microbiota. 16S high-throughput sequencing and bioinformatic analyses indicated that fermentation of carrot juice could significantly change the composition of the human gut microbiome. Interestingly, carrot juice remarkably increased the abundances of beneficial bacteria, including Lactobacillus fermentum, Lactobacillus salivarius, Lactobacillus mucosae and Bacteroides uniformis and decreased the population of opportunistic pathogenic bacteria, such as Enterococcus faecium in the gut. Collectively, our study illustrates a favorable effect of carrot juice on the human gut microbiota and lays a foundation for the development of carrot juice as a novel prebiotic agent.

Many of the fundamental molecules of life share extraordinary pigment-like optical properties in the long-wavelength UV-C spectral region. These include strong photon absorption and rapid (sub pico-second) dissipation of the induced electronic excitation energy into heat through peaked conical intersections. These properties have been attributed to a ``natural selection'' of molecules resistant to the dangerous UV-C light incident on Earth's surface during the Archean. In contrast, the ``thermodynamic dissipation theory for the origin of life'' argues that, far from being detrimental, UV-C light was, in fact, the thermodynamic potential driving the dissipative structuring of life at its origin. The optical properties were thus the thermodynamic ``design goals'' of microscopic dissipative structuring of organic UV-C pigments, today known as the ``fundamental molecules of life'', from common precursors under this light. This ``UV-C Pigment World'' evolved towards greater solar photon dissipation through more complex dissipative structuring pathways, eventually producing visible pigments to dissipate less energetic, but higher intensity, visible photons, up to wavelengths of the ``red-edge''. The propagation and dispersal of organic pigments, catalyzed by animals, and their coupling with abiotic dissipative processes, such as the water cycle, culminated in the apex photon dissipative structure, today's biosphere.

The diagnosis and management of cow's milk allergy (CMA) is a topic of debate and controversy. We aimed to compare the opinions of expert groups from the Middle East (n=14) and the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) (n=13). These Expert groups voted on statements developed by the ESPGHAN group and published in a recent position paper. The voting outcome was compared. Overall, there was consensus amongst both groups of experts. Most experts agreed that symptoms of crying, irritability and colic, as single manifestations, do not suggest CMA. They agreed that amino-acid-based formula (AAF) should be reserved for severe cases (e.g. malnutrition and anaphylaxis) and that there is insufficient evidence to recommend a step-down approach. There was no consensus on the statement that a cow’s milk-based extensively hydrolysed formula (eHF) should be the first choice as a diagnostic elimination diet in mild/moderate cases. Although the statements regarding the role of hydrolysed rice formula as a diagnostic and therapeutic elimination diet were accepted, 3/27 disagreed. The votes regarding soy formula highlight the differences in opinion in the role of soy protein in CMA dietary treatment. Generally, soy-based formula is seldom available in the Middle East region. All ESPGHAN experts agreed that there was no added value of probiotics, prebiotics, and synbiotics to the efficacy of elimination diets, whereas 3/14 of the Middle East group thought there was sufficient evidence. Therefore, there is not a consensus on the optimal diagnostic and therapeutic elimination diet for CMA, but the first-choice elimination diet and the stepwise management approach reveal some differences.

The microbiota–gut–brain axis has garnered increasing attention in recent years for its role in various health conditions, including neuroinflammatory disorders like complex regional pain syndrome (CRPS). CRPS is a debilitating condition characterized by chronic neuropathic pain, and its etiology and pathophysiology remain elusive. Emerging research suggests that alterations in the gut microbiota composition and function could play a significant role in CRPS development and progression. Our paper explores the implications of microbiota in CRPS and the potential therapeutic role of boron (B). Studies have demonstrated that individuals with CRPS often exhibit dysbiosis, with imbalances in beneficial and pathogenic gut bacteria. Dysbiosis can lead to increased gut permeability and systemic inflammation, contributing to the chronic pain experienced in CRPS. B, an essential trace element, has shown promise in modulating the gut microbiome positively and exerting anti-inflammatory effects. Recent preclinical and clinical studies suggest that B supplementation may alleviate neuropathic pain and improve CRPS symptoms by restoring microbiota balance and reducing inflammation. Our review highlights the complex interplay between microbiota, inflammation, and neuropathic pain in CRPS and underscores the potential of B as a novel therapeutic approach to target the microbiota–gut–brain axis, offering hope for improved management of this challenging condition.

Homochirality is an obvious feature of life on Earth. On the other hand, extraterrestrial samples contain largely racemic compounds. The same is true for any common organic synthesis. Therefore, it has been a perplexing puzzle for decades how these racemates could have formed enantiomerically enriched fractions as a basis for the origin of homochiral life forms. Numerous hypotheses have been put forward as to how preferentially homochiral molecules could have formed and accumulated on Earth. In this article, it is shown that homochirality of the abiotic organic pool at the time of formation of the first self-replicating molecules is not necessary and not even probable. It is proposed to abandon the notion of a molecular ensemble and to focus on the level of individual molecules. Although the formation of the first self-replicating, most likely homochiral molecule is a seemingly improbable event, on a closer look, it is almost inevitable that homochiral molecules have formed simply on a statistical basis. In this case, the non-selective leap to homochirality would be one of the first steps in chemical evolution directly out of a racemic “ocean”. Moreover, most studies focus on the chirality of the primordial monomers with respect to an asymmetric carbon atom. However, any polymer with a minimal size that allows folding to a secondary structure, would spontaneously lead to asymmetric higher structures (conformations). Most of the functions of these polymers would be influenced by this inherently asymmetric folding. To summarize, simple and universal mechanisms may have led to homochiral self-replicating systems in the context of chemical evolution. A homochiral monomer pool is deemed unnecessary and probably never existed on primordial Earth.

Theories on life’s origin generally acknowledge the advantage of a semi-permeable vesicle (protocell) for enhancing the chemical reaction-diffusion processes involved in abiogenesis. However, more and more evidence indicates that the origin of life concerned the photo-chemical dissipative structuring of the fundamental molecules under UV-C light. In this paper, we analyze the Mie UV scattering properties of such a vesicle made from long chain fatty acids. We find that the vesicle could have provided early life with a shield from the faint, but dangerous, hard UV-C ionizing light (180-210 nm) that probably bathed Earth’s surface from before the origin of life and until perhaps 1,500 million years after, until the formation of a protective ozone layer as a result of the evolution of oxygenic photosynthesis.

Information is the currency of life, but the origin of prebiotic information remains a mystery. We propose transitional pathways from the cosmic building blocks of life to the complex prebiotic organic chemistry that led to the origin of information systems. The prebiotic information system, specifically the genetic code, is segregated, linear, and digital and probably appeared during biogenesis four billion years ago. In the peptide/RNA world, lipid membranes randomly encapsulated amino acids, RNA, and protein molecules, drawn from the prebiotic soup, to initiate a molecular symbiosis inside the protocells. This endosymbiosis led to the hierarchical emergence of several requisite components of the translation machine: tRNAs, aaRS, mRNAs, and ribosomes. When assembled in the right order, the translation machine created biosynthetic polypeptides, a process that transferred information from mRNAs to proteins. This was the beginning of the prebiotic information age. The molecular attraction between tRNA and amino acids led to different stages of the translation machines and the genetic code. tRNA is an ancient molecule that designed and built mRNA for storing the information of its cognate amino acid. Each mRNA strand became the storage device for the genetic information that encoded the amino acid sequences in triplet nucleotides. As information appeared in the digital languages of the codon within mRNA, and the genetic code for protein synthesis evolved, the prebiotic chemistry then became more organized and directional. The origin of the genetic code is enigmatic; herein we propose an evolutionary explanation: the demand for a wide range of specific enzymes in the peptide/RNA world was the main selective pressure for the origin of information-directed protein synthesis. We review three main concepts on the origin and evolution of the genetic code: the stereochemical theory, the coevolution theory, and the adaptive theory. These three theories are compatible with our coevolution model of the translation machines and the genetic code. We suggest biosynthetic pathways as the origin of the specific translation machines which provided the framework for the origin of the genetic code. During translation, the genetic code developed in three stages coincident with the refinement of the translation machines: GNC code developed by the pre-tRNA/pre-aaRS /pre-mRNA machine, SNS code by the tRNA/aaRS/mRNA machine, and finally the universal genetic code by the tRNA/aaRS/mRNA/ribosome machine. Our hypothesis provides the logical and incremental steps for the origin of the programmed protein synthesis. In order to understand the prebiotic information system better, we converted letter codons into numerical codons in the Universal Genetic Code Table. We have developed a software called CATI (Codon-Amino Acid-Translator-Imitator) to translate randomly chosen numerical codons into corresponding amino acids and vice versa. This conversion has granted us insight into how the translation might have worked in the peptide/RNA world. There is great potential in the application of numerical codons to bioinformatics such as barcoding, DNA mining, or DNA fingerprinting. We constructed the likely biochemical pathways for the origin of translation and the genetic code using the Model-View-Controller (MVC) software framework, and the translation machinery step-by-step. Using AnyLogic software we were able to simulate and visualize the entire evolution of the translation machines and the genetic code. The results indicate that the emergence of the information age from the peptide/RNA world was a watershed event in the origin of life about four billion years ago.