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Abstract Background The global probiotics dietary supplements market size is continuously growing. To overcome probiotics’ health concerns, metabiotics are recognized as a safer alternative. Aiming to deal with the escalating antimicrobial resistance, the current work demonstrates synergistic metabiotic-antibiotic combinations against antibiotic-resistant pathogens. Methods The probiotic properties of lactic acid bacteria (LAB) strains isolated from 3 commercial dietary supplements were characterized in vitro. The combinations of the cell-free supernatants (CFS) of selected probiotic strains and conventional antibiotics against Staphylococcus aureus and Escherichia coli clinical isolates were evaluated using the time-kill assay. To our knowledge, the current literature lacks sufficient time-kill assay studies revealing the kinetics of such metabiotic-antibiotic combinations against S. aureus and E. coli. Results Four LAB strains isolated from dietary supplements as well as two reference strains were included in this study. The isolated LAB strains were identified by MALDI-TOF mass spectrometry as follows: P2: Lactobacillus acidophilus, P3: Lactiplantibacillus plantarum, P4: Lacticaseibacillus rhamnosus, and P5: Pediococcus acidilactici. The identification matched with that annotated by the manufacturers, except for P3. The tested strains could resist the acidic environment at pH 3. Excluding P2, the examined strains showed less than 1 log reduction in survivors upon the addition of reconstituted skimmed milk to pepsin at pH 2 and displayed an acceptable tolerance to 0.3% ox-bile. All the strains tolerated pancreatin. The hydrophobicity and autoaggregation capacities ranged between 7–92% and 36–66%, respectively. P2 was excluded owing to its inferior probiotic potential. Although the remaining strains showed excellent growth at 0.2% phenol, their growth was reduced at higher concentrations. L. plantarum and P. acidilactici strains possessed bile salt hydrolysis activity. The time-kill assay revealed promising synergistic activities of the combinations of CFS of L. rhamnosus P4 with either ceftazidime or gentamicin against E. coli and with only ceftazidime against S. aureus, as well as CFS of P. acidilactici P5 and ceftazidime against S. aureus. Conclusions Strict identification and evaluation of the probiotic strains incorporated in dietary supplements is crucial to ensure their safety and efficacy. The CFS of probiotics could be utilized to formulate novel biotherapeutics targeting problematic pathogens. However, future in vivo studies are required to evaluate the appropriate treatment regimen.

Lactobacillus species are widely recognized for their probiotic potential, focusing on their mechanisms of health benefits and protection. Here we conducted an in vitro investigation of the probiotic potential with a role in microbiome homeostasis of four strains: Lactiplantibacillus plantarum L6 and F53, Ligilactobacillus salivarius 1, and Lactobacillus helveticus 611. A broad spectrum of antibacterial and antifungal activity was determined. The strain-specific inhibition of Staphylococcus aureus, Streptococcus mutans, Escherichia coli, Pseudomonas aeruginosa, and saprophytic/toxigenic fungi makes them promising as protective cultures. DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid) measurements showed that tested samples had strain-specific capacity for scavenging of radicals. The molecular base for the antioxidant potential of two lyophilized forms of active strains was investigated by electron paramagnetic resonance spectroscopy. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, with fractions of the most active postbiotics obtained by SEC-FPLC (fast protein liquid chromatography) analysis, showed a wide variety of effects on the growth of a K562 myeloid leukemia cell line. The IC50 (half-maximal inhibitory concentration) of L. salivarius 1 was determined to be 46.15 mg/mL. The proven in vitro functionality of the selected lactobacilli make them suitable for development of target probiotics with specific beneficial effects expected in vivo. Further investigations on produced postbiotics and safety have to be completed before they can be considered as scientifically proven probiotic strains. [ABSTRACT FROM AUTHOR]

Background: The global probiotics dietary supplements market size is continuously growing. To overcome probiotics' health concerns, metabiotics are recognized as a safer alternative. Aiming to deal with the escalating antimicrobial resistance, the current work demonstrates synergistic metabiotic-antibiotic combinations against antibiotic-resistant pathogens. Methods: The probiotic properties of lactic acid bacteria (LAB) strains isolated from 3 commercial dietary supplements were characterized in vitro. The combinations of the cell-free supernatants (CFS) of selected probiotic strains and conventional antibiotics against Staphylococcus aureus and Escherichia coli clinical isolates were evaluated using the time-kill assay. To our knowledge, the current literature lacks sufficient time-kill assay studies revealing the kinetics of such metabiotic-antibiotic combinations against S. aureus and E. coli. Results: Four LAB strains isolated from dietary supplements as well as two reference strains were included in this study. The isolated LAB strains were identified by MALDI-TOF mass spectrometry as follows: P2: Lactobacillus acidophilus, P3: Lactiplantibacillus plantarum, P4: Lacticaseibacillus rhamnosus, and P5: Pediococcus acidilactici. The identification matched with that annotated by the manufacturers, except for P3. The tested strains could resist the acidic environment at pH 3. Excluding P2, the examined strains showed less than 1 log reduction in survivors upon the addition of reconstituted skimmed milk to pepsin at pH 2 and displayed an acceptable tolerance to 0.3% ox-bile. All the strains tolerated pancreatin. The hydrophobicity and autoaggregation capacities ranged between 7–92% and 36–66%, respectively. P2 was excluded owing to its inferior probiotic potential. Although the remaining strains showed excellent growth at 0.2% phenol, their growth was reduced at higher concentrations. L. plantarum and P. acidilactici strains possessed bile salt hydrolysis activity. The time-kill assay revealed promising synergistic activities of the combinations of CFS of L. rhamnosus P4 with either ceftazidime or gentamicin against E. coli and with only ceftazidime against S. aureus, as well as CFS of P. acidilactici P5 and ceftazidime against S. aureus. Conclusions: Strict identification and evaluation of the probiotic strains incorporated in dietary supplements is crucial to ensure their safety and efficacy. The CFS of probiotics could be utilized to formulate novel biotherapeutics targeting problematic pathogens. However, future in vivo studies are required to evaluate the appropriate treatment regimen. [ABSTRACT FROM AUTHOR]

ABSTRACTGut microbiota is an important modulator of human health and contributes to high inter-individual variation in response to food and pharmaceutical ingredients. The clinical outcomes of interventions with prebiotics, probiotics, and synbiotics have been mixed and often unpredictable, arguing for novel approaches for developing microbiome-targeted therapeutics. Here, we review how the gut microbiota determines the fate of and individual responses to dietary and xenobiotic compounds via its immense metabolic potential. We highlight that microbial metabolites play a crucial role as targetable mediators in the microbiota-host health relationship. With this in mind, we expand the concept of synbiotics beyond prebiotics’ role in facilitating growth and engraftment of probiotics, by focusing on microbial metabolism as a vital mode of action thereof. Consequently, we discuss synbiotic compositions that enable the guided metabolism of dietary or co-formulated ingredients by specific microbes leading to target molecules with beneficial functions. A workflow to develop novel synbiotics is presented, including the selection of promising target metabolites (e.g. equol, urolithin A, spermidine, indole-3 derivatives), identification of suitable substrates and producer strains applying bioinformatic tools, gut models, and eventually human trials.In conclusion, we propose that discovering and enabling specific substrate–microbe interactions is a valuable strategy to rationally design synbiotics that could establish a new category of hybrid nutra-/pharmaceuticals.

Background. Symptomatic uncomplicated diverticular colon disease (SNDCD) is a common condition that significantly affects the quality of life of patients. One of the main therapeutic targets in SNDCD is the microbiota. Aim. To evaluate the efficacy and safety of microbiocenosis-based therapy (prebiotic Mucofalk + metabiotic Zakofalk) in relieving symptoms of SNDCD and maintaining asymptomatic remission. Materials and methods. The study included 60 patients with clinically apparent SNDCD. For 3 months, they were treated with Mukofalk and Zakofalk and then followed up for another 3 months. Parameters such as treatment efficacy, satisfaction and compliance were evaluated, as well as change of short-chain fatty acids in feces using gas-liquid chromatography was measured. Results. A statistically significant improvement of all assessed symptoms (abdominal pain, constipation, diarrhea, flatulence, tenesmus) was observed after 3 months of therapy. Relapse of abdominal pain and bowel movement disorders (constipation) after completion of therapy were observed in 7 (11.6%) subjects. The compliance study showed that more than 80% of the required number of sachets/tablets was taken by more than 80% of patients. At the end of follow-up, 49 (81.7%) patients rated their outcomes as "excellent" and 11 (18.3%) as "good". During treatment, there was a significant tendency to increase the absolute content of butyric acid in feces. Conclusion. Microbiocenosis-based therapy with the prebiotic Mukofalk and the metabiotic Zakofalk is effective and safe for treating SNDCD and preventing the recurrence of symptoms and disease complications. The therapy is associated with excellent and good satisfaction and a high compliance to treatment. Therapy with Mukofalk and Zakofalk resulted in the normalization of the intestinal microbiota.

Introduction: Lactic acid bacteria (LAB) produce various metabolites (i.e. metabiotics) with inhibitory capacity towards harmful foodborne pathogens. Methods: This study aimed to design several antimicrobial formulations based on metabiotics obtained from different native LAB species (Lactobacillus pentosus UTNGt5, Lactococcus lactis UTNGt28, and Weissella cibaria UTNGt21O) and to detect the possible mode of action towards two multidrug resistant Staphylococcus spp. strains isolated from avocado (Persea nubigena var. guatemalensis) fruits. Additionally, the formulation with the highest inhibitory activity was tested ex vitro on avocados at the immature (firm) ripeness stage to evaluate their effect on microorganisms' growth and fruit quality attributes post-harvest. Results and discussion: Out of the top five formulations showing the highest bactericidal effect in vitro at their minimum inhibitory concentration (1 x MIC) on both Staphylococcus spp. targets one candidate annotated P11 (consisting of UTNGt21O and UTNGt28; 1:3, v/v) was selected. Co-cultivation of Staphylococcus strains with P11 formulation results in cell viability reduction by 98%, by impairing the integrity of the cell membrane inducing cytoplasm molecule content leakage, protein profile changes, and finally bacterial death. Even though the total coliforms, Staphylococcus spp., Enterobacter spp., molds, and yeasts counts were not fully eliminated by day 13 of storage, a statistically significant reduction (p < 0.05) in viable cell counts were observed by day 8 upon the P11 treatment compared with non-treated control (C) and treated with a commercial disinfectant (T1) samples, suggesting that P11 formulation inhibited microbial colonization during storage. Likewise, no visible dark spots were observed on the mesocarp (pulp) upon the treatment with P11, whereas T1 and C fruits showed greater dark spots on the pulp as indicative of damage. The quality attributes, such as pH, total soluble solids, total titratable acidity, antioxidant capacity, and total polyphenol content, were not affected by the treatment. Principal Component Analysis (PCA) conducted on these five variables showed a clear separation of samples according to the maturity stage regardless of the treatment. Conclusion: These results suggest that the active metabolites from LAB strains might create a barrier between the exocarp and mesocarp, inhibiting the microorganisms colonization, reducing fruit damage, and lengthening the fruit quality and safety after harvest. [ABSTRACT FROM AUTHOR]

Recently, there has been an increasing interest in the association of gut microbiota with health conditions and the potentially beneficial role of several types of biotics in several population groups, including children and adolescents. Children and adolescents comprise a unique population group due their rapid growth rates, high nutritional requirements, the immaturity of their immune system in early life, and their susceptibility to infectious diseases. The aim of the present study is to investigate the role and limitations of the administration of biotics in specific conditions affecting children and adolescents. A narrative review of related articles published on PubMed up to October 2023 was conducted. The administration of biotics has been evaluated in several health conditions among children and adolescents, such as the treatment and prevention of infectious diarrhea, the prevention of diarrhea after the use of antibiotics, the prevention of necrotizing enterocolitis, the treatment of functional gastrointestinal diseases, such as infant colic, functional abdominal pain, and irritable bowel syndrome, the eradication of H. pylori, the treatment of ulcerative colitis and pouchitis, and the prevention of atopic dermatitis, and the findings indicate improved symptoms and various beneficial health outcomes. However, some limitations have been identified regarding probiotics' use. In conclusion, biotics may have a beneficial impact in several health conditions among children and adolescents. There is a need for additional randomized, controlled clinical studies on the effects of the administration of biotics in children and particularly in adolescents and young adults. [ABSTRACT FROM AUTHOR]

Scientific relevance. A promising option for dysbiosis correction is the use of metabiotics, products based on metabolites of probiotic microorganisms. During fermentation, Bacillus subtilis bacteria (strains 3H and 1719) produce metabolites that exhibit probiotic properties in vitro. These observations in vitro motivate an in vivo investigation of B. subtilis metabolite effects on colonic mucosal microbiota in mice in experimentally induced dysbiosis and an assessment of the potential of B. subtilis metabolites as metabiotics.Aim. The authors aimed to compare the probiotic activity of B. subtilis 3H and B. subtilis 1719 metabolites and a commercial metabiotic in antibiotic-induced dysbiosis in mice.Materials and methods. The authors induced experimental dysbiosis in BALB/c mice weighing 18–20 g by intraperitoneal injection of gentamicin. For subsequent correction, the test groups received sorbent-bound B. subtilis metabolites, and the comparison group received a commercial metabiotic containing B. subtilis metabolites (VKPM B-2335(3)3) via intragastric injection for 21 days. The quantitative and qualitative analysis of colonic mucosal microbiota included microbial culturing and colony identification by MALDI-TOF mass spectrometry.Results. Antibiotic-induced colonic dysbiosis in mice manifested itself as a decrease in the dominant microbiota and an increase in opportunistic pathogens. After 7 days of metabolite administration, the Lactobacillus population returned to normal in all treatment groups. The mice that received B. subtilis 3H metabolites showed the best results: their Lactobacillus spp. composition corresponded to that of intact animals. The content of Lac+ Escherichia coli returned to 100% in all treatment groups. After 21 days of metabolite administration, the authors observed the elimination of bacteria (Rodentibacter spp., Aerococcus spp.) and fungi (Trichosporon spp., Kazachstania spp.) in the B. subtilis 3H group; Trichosporon spp. (no effect on Kazachstania spp.) in the B. subtilis 1719 group; and Enterococcus spp., Kazachstania spp., and Trichosporon spp. (no effect on Rodentibacter spp. and Aerococcus spp.) in the commercial metabiotic group.Conclusions. Metabolites of B. subtilis strains 3H and 1719 help to restore the diversity and abundance of colonic microbiota in antibiotic-induced dysbiosis. The differences observed in microbiota re-establishment in the treatment groups indicate that there is interstrain variability in the probiotic activity of B. subtilis metabolites.

Lactobacillus species are widely recognized for their probiotic potential, focusing on their mechanisms of health benefits and protection. Here we conducted an in vitro investigation of the probiotic potential with a role in microbiome homeostasis of four strains: Lactiplantibacillus plantarum L6 and F53, Ligilactobacillus salivarius 1, and Lactobacillus helveticus 611. A broad spectrum of antibacterial and antifungal activity was determined. The strain-specific inhibition of Staphylococcus aureus, Streptococcus mutans, Escherichia coli, Pseudomonas aeruginosa, and saprophytic/toxigenic fungi makes them promising as protective cultures. DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid) measurements showed that tested samples had strain-specific capacity for scavenging of radicals. The molecular base for the antioxidant potential of two lyophilized forms of active strains was investigated by electron paramagnetic resonance spectroscopy. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, with fractions of the most active postbiotics obtained by SEC-FPLC (fast protein liquid chromatography) analysis, showed a wide variety of effects on the growth of a K562 myeloid leukemia cell line. The IC50 (half-maximal inhibitory concentration) of L. salivarius 1 was determined to be 46.15 mg/mL. The proven in vitro functionality of the selected lactobacilli make them suitable for development of target probiotics with specific beneficial effects expected in vivo. Further investigations on produced postbiotics and safety have to be completed before they can be considered as scientifically proven probiotic strains.

This paper discusses the results of research related to cultivation of the probiotic microorganism B. subtilis on a grain-based nutrient medium of naked oat (Avena nuda) and studies the possibility of using metabolites as a liquid dietary supplement to correct microbiocenosis gastrointestinal tract dis-orders in early-weaned piglets. The weight fraction of proteinogenic amino acids in the experimental probiotic suspensions was determined by means of capillary electrophoresis. The metabolic activity of Bacillus subtilis DSM-32424 strain was studied on both sprouted as well as non-sprouted naked oat (Avena nuda) ‘Nemchinovsky’ variety grain-based nutrient medium. It was proved that the maximum microbial count reached 4.9×107 CFU/cm3 on the 6th day of cultivation on the medium based on sprouted naked oat. The use of dietary supplement based on Bacillus subtilis DSM-32424 strain in amount of at least 1×109 CFU/pig had a positive impact in terms of the formation of microbiocenosis in animals at the time of transferring piglets to plant diet.

IntroductionLactic acid bacteria (LAB) produce various metabolites (i.e. metabiotics) with inhibitory capacity towards harmful foodborne pathogens.MethodsThis study aimed to design several antimicrobial formulations based on metabiotics obtained from different native LAB species (Lactobacillus pentosus UTNGt5, Lactococcus lactis UTNGt28, and Weissella cibaria UTNGt21O) and to detect the possible mode of action towards two multidrug resistant Staphylococcus spp. strains isolated from avocado (Persea nubigena var. guatemalensis) fruits. Additionally, the formulation with the highest inhibitory activity was tested ex vitro on avocados at the immature (firm) ripeness stage to evaluate their effect on microorganisms’ growth and fruit quality attributes post-harvest.Results and discussionOut of the top five formulations showing the highest bactericidal effect in vitro at their minimum inhibitory concentration (1 x MIC) on both Staphylococcus spp. targets one candidate annotated P11 (consisting of UTNGt21O and UTNGt28; 1:3, v/v) was selected. Co-cultivation of Staphylococcus strains with P11 formulation results in cell viability reduction by 98%, by impairing the integrity of the cell membrane inducing cytoplasm molecule content leakage, protein profile changes, and finally bacterial death. Even though the total coliforms, Staphylococcus spp., Enterobacter spp., molds, and yeasts counts were not fully eliminated by day 13 of storage, a statistically significant reduction (p

This paper discusses the results of research related to cultivation of the probiotic microorganism B. subtilis on a grain-based nutrient medium of naked oat (Avena nuda) and studies the possibility of using metabolites as a liquid dietary supplement to correct microbiocenosis gastrointestinal tract disorders in early-weaned piglets. The weight fraction of proteinogenic amino acids in the experimental probiotic suspensions was determined by means of capillary electrophoresis. The metabolic activity of Bacillus subtilis DSM-32424 strain was studied on both sprouted as well as non-sprouted naked oat (Avena nuda) 'Nemchinovsky' variety grain-based nutrient medium. It was proved that the maximum microbial count reached 4.9×107 CFU/cm3 on the 6th day of cultivation on the medium based on sprouted naked oat. The use of dietary supplement based on Bacillus subtilis DSM-32424 strain in amount of at least 1×109 CFU/pig had a positive impact in terms of the formation of microbiocenosis in animals at the time of transferring piglets to plant diet. [ABSTRACT FROM AUTHOR]

Depression is a common and complex mental and emotional disorder that causes disability, morbidity, and quite often mortality around the world. Depression is closely related to several physical and metabolic conditions causing metabolic depression. Studies have indicated that there is a relationship between the intestinal microbiota and the brain, known as the gut–brain axis. While this microbiota–gut–brain connection is disturbed, dysfunctions of the brain, immune system, endocrine system, and gastrointestinal tract occur. Numerous studies show that intestinal dysbiosis characterized by abnormal microbiota and dysfunction of the microbiota–gut–brain axis could be a direct cause of mental and emotional disorders. Traditional treatment of depression includes psychotherapy and pharmacotherapy, and it mainly targets the brain. However, restoration of the intestinal microbiota and functions of the gut–brain axis via using probiotics, their metabolites, prebiotics, and healthy diet may alleviate depressive symptoms. Administration of probiotics labeled as psychobiotics and their metabolites as metabiotics, especially as an adjuvant to antidepressants, improves mental disorders. It is a new approach to the prevention, management, and treatment of mental and emotional illnesses, particularly major depressive disorder and metabolic depression. For the effectiveness of antidepressant therapy, psychobiotics should be administered at a dose higher than 1 billion CFU/day for at least 8 weeks. [ABSTRACT FROM AUTHOR]

Metabiotics are the structural components of probiotic bacteria, functional metabolites, and/or signaling molecules with numerous beneficial properties. A novel Lactococcus lactis strain, UTNCys6-1, was isolated from wild Amazonian camu-camu fruits (Myrciaria dubia), and various functional metabolites with antibacterial capacity were found. The genome size is 2,226,248 base pairs, and it contains 2248 genes, 2191 protein-coding genes (CDSs), 50 tRNAs, 6 rRNAs, 1 16S rRNA, 1 23S rRNA, and 1 tmRNA. The average GC content is 34.88%. In total, 2148 proteins have been mapped to the EggNOG database. The specific annotation consisted of four incomplete prophage regions, one CRISPR-Cas array, six genomic islands (GIs), four insertion sequences (ISs), and four regions of interest (AOI regions) spanning three classes of bacteriocins (enterolysin_A, nisin_Z, and sactipeptides). Based on pangenome analysis, there were 6932 gene clusters, of which 751 (core genes) were commonly observed within the 11 lactococcal strains. Among them, 3883 were sample-specific genes (cloud genes) and 2298 were shell genes, indicating high genetic diversity. A sucrose transporter of the SemiSWEET family (PTS system: phosphoenolpyruvate-dependent transport system) was detected in the genome of UTNCys6-1 but not the other 11 lactococcal strains. In addition, the metabolic profile, antimicrobial susceptibility, and inhibitory activity of both protein–peptide extract (PPE) and exopolysaccharides (EPSs) against several foodborne pathogens were assessed in vitro. Furthermore, UTNCys6-1 was predicted to be a non-human pathogen that was unable to tolerate all tested antibiotics except gentamicin; metabolized several substrates; and lacks virulence factors (VFs), genes related to the production of biogenic amines, and acquired antibiotic resistance genes (ARGs). Overall, this study highlighted the potential of this strain for producing bioactive metabolites (PPE and EPSs) for agri-food and pharmaceutical industry use. [ABSTRACT FROM AUTHOR]

IntroductionAccording to WHO, antibiotic resistance is increasing to hazardous levels worldwide. Candidiasis often occurs after taking antibiotics. Therefore, antibiotic resistance is a global problem and searching for antibacterial agents is necessary.AimTo determine the antimicrobial activity of bacterial lysate of Lactobacillus (L.) rhamnosus DV separately and with plant extracts against bacterial and yeast test cultures.Material and methodsAntimicrobial activity of Del-Immune V® (cell wall and DNA fragments from a L. rhamnosus DV) separately and with cinnamon, beetroot, and blackcurrant extracts was determined by the minimum inhibitory concentration (MIC). Twofold serial dilutions determined the MIC in previously prepared meat-peptone broth (MPB) for bacteria and liquid wort for yeast. In the study, gram-negative (Escherichia coli IEM-1, Proteus vulgaris PА-12, Pseudomonas sp. MI-2, L. rhamnosus 13/2) and gram-positive (Bacillus (B.) subtilis BТ-2, Staphylococcus aureus BМС-1) bacteria, as well as yeast (Candida (C.) albicans D-6, C. tropicalis PE-2, C. utilis BVS-65) were used as test cultures.ResultsThe MIC for the studied bacterial test cultures after application of L. rhamnosus DV bacterial lysates was from 1.0 ± 0.05 mg/mL to 12.5 ± 0.63 mg/mL, which was significantly less than that of the thermally inactivated control (MIC from 125.0 ± 6.25 mg/mL to 250.0 ± 12.5 mg/mL). B. subtilis BT-2 culture was the least sensitive to the action of the bacterial lysate (MIC—12.5 ± 0.63 mg/mL). It showed the best antibacterial and antifungal effect bacterial lysate with the phytonutrient blackcurrant.ConclusionsIt was demonstrated that bacterial lysate of lactic acid bacteria L. rhamnosus DV exhibits antibacterial and antifungal properties during direct contact with pathogenic agents.

Recently, there has been an increasing interest in the association of gut microbiota with health conditions and the potentially beneficial role of several types of biotics in several population groups, including children and adolescents. Children and adolescents comprise a unique population group due their rapid growth rates, high nutritional requirements, the immaturity of their immune system in early life, and their susceptibility to infectious diseases. The aim of the present study is to investigate the role and limitations of the administration of biotics in specific conditions affecting children and adolescents. A narrative review of related articles published on PubMed up to October 2023 was conducted. The administration of biotics has been evaluated in several health conditions among children and adolescents, such as the treatment and prevention of infectious diarrhea, the prevention of diarrhea after the use of antibiotics, the prevention of necrotizing enterocolitis, the treatment of functional gastrointestinal diseases, such as infant colic, functional abdominal pain, and irritable bowel syndrome, the eradication of H. pylori, the treatment of ulcerative colitis and pouchitis, and the prevention of atopic dermatitis, and the findings indicate improved symptoms and various beneficial health outcomes. However, some limitations have been identified regarding probiotics’ use. In conclusion, biotics may have a beneficial impact in several health conditions among children and adolescents. There is a need for additional randomized, controlled clinical studies on the effects of the administration of biotics in children and particularly in adolescents and young adults.

Introduction. Diverticular disease of the colon is one of the most common gastrointestinal diseases. During the last 30–40 years, there has been a “rejuvenation” of the disease. Today, the prevalence of the disease in people under 40 years of age is 5–10%, and therefore the costs of diagnostic testing and treatment are gradually increasing, which makes the disease socially significant.Aim. To study the clinical features of diverticular disease, the features of diagnosis and treatment, and prophylactic approaches. The specific objectives of the analysis were to study epidemiology; study the role and a necessary minimum set of laboratory diagnostic test methods for the diagnosis of diverticular disease; study the incidence rate of SIBO and its impact on the clinic presentation and treatment; develop an algorithm for the diagnosis, treatment, prevention, and management of patients with diverticular disease.Materials and methods. A total of 195 patients with different forms of diverticular disease were examined. As diagnostic tests, we used blood tests, stool tests, biochemical tests; inflammatory tests: calprotectin, CRP, fibrinogen, ferritin; ultrasound imaging, irrigoscopy, CT, NMR, colonoscopy (if medically required); clinical manifestations at different stages of the course of diverticular disease. 5-aminosalicylates were used to treat exacerbation with inflammation; alpha-normix and motility regulators were used to treat exacerbation without signs of inflammation.Results. On the basis of the study results, we suggested an algorithm for the diagnosis, management and treatment of patients with diverticular disease. According to the particulars of the management, it is reasonable to divide all patients with diverticular disease into three groups: 1) patients who underwent acute diverticulitis; 2) patients with uncomplicated diverticular disease; 3) patients with complicated diverticular disease.Conclusions. The first two groups should be followed up by a gastroenterologist/general practitioner, the third group should be followed up by a surgeon. The patient tested positive for SIBO should receive drugs to eradicate SIBO. The treatment regimens for exacerbation of diverticular disease are proposed.

Depression is a common and complex mental and emotional disorder that causes disability, morbidity, and quite often mortality around the world. Depression is closely related to several physical and metabolic conditions causing metabolic depression. Studies have indicated that there is a relationship between the intestinal microbiota and the brain, known as the gut–brain axis. While this microbiota–gut–brain connection is disturbed, dysfunctions of the brain, immune system, endocrine system, and gastrointestinal tract occur. Numerous studies show that intestinal dysbiosis characterized by abnormal microbiota and dysfunction of the microbiota–gut–brain axis could be a direct cause of mental and emotional disorders. Traditional treatment of depression includes psychotherapy and pharmacotherapy, and it mainly targets the brain. However, restoration of the intestinal microbiota and functions of the gut–brain axis via using probiotics, their metabolites, prebiotics, and healthy diet may alleviate depressive symptoms. Administration of probiotics labeled as psychobiotics and their metabolites as metabiotics, especially as an adjuvant to antidepressants, improves mental disorders. It is a new approach to the prevention, management, and treatment of mental and emotional illnesses, particularly major depressive disorder and metabolic depression. For the effectiveness of antidepressant therapy, psychobiotics should be administered at a dose higher than 1 billion CFU/day for at least 8 weeks.

The purpose of the study was to analyze validity and effectiveness of simultaneous application of bacterial probiotics and antibacterial antibiotics during antimicrobial therapy. Materials and methods. The review includes materials of foreign and domestic researchers published in modern periodical and monographic literature. Results. The conceptual material of the main terms and definitions of «ideal» antibiotics and probiotics is presented. The dominant role of bacterial probiotics in the group of medical probiotics in the Russian pharmaceutical market was established. A comparative assessment of the data on the passportization, identification, and sensitivity to antibiotics of a number of commercial probiotic cultures was carried out. The article considers theoretical and practical joint use of antibiotics, probiotics, and metabiotics during antimicrobial therapy. Conclusion. The current practice ofjoint use of probiotics and antibiotics in the process of antimicrobial therapy is extremely limited and indicates the presence of serious circumstances that reduce the effectiveness of probiotic therapy. One of the directions that exclude this situation is the use of metabiotics in the form of medications.

Objective of the study: comparative evaluation of the bacteriotropic activity of Actoflor-S metabiotic and the exometabolic bifidobacteria complex.Materials and methods: in our work we used Actoflor-S dietary supplement as oral solution in 2 ml drop tubes (Solopharm). As a comparator drug, we used an exometabolite complex from the culture fluid of strain Bifidobacterium bifidum 1 obtained by method of ultrafiltration using separation apparatus with HOMM 15 kDa. We studied the stimulating effect of metabolite compositions on the acid forming activity and dynamics of the accumulation of lactobacilli Lactobacillus plantarum 8P-A3. Antagonistic activity against enterobacteria was determined in the test of inhibition of bioluminescence of the indicator strain Escherichia coli lum+ and quantified as an index of antibacterial activityResults and discussions. A comparative study of the effects of metabiotics on the acid forming activity of lactobacilli showed that both drugs have a pronounced stimulating effect on the probiotic strain L. plantarum. A comparative study of the effects of metabiotics on the model test strain of enterobacteria showed that whole preparations quickly and significantly (by more than 90%) inhibit the bioluminescence of E.coli lum+. Preparation dilutions 1:10 and 1:100 discovered significant differences in their activity. Given equal pH values (5.8 ± 0.1), Actoflor-S (dilution 1:10) inhibited the luminescence of E. coli lum + to a greater degree, exceeding almost 2 times the indicators of the metabolite bifidobacteria complex. It is revealing that Actoflor-S diluted 1:10 is not inferior to the whole preparation in terms of the level of effect on the test strain culture. What calls attention to itself is that large dilutions of UFLC of bifidobacteria after a short period of inhibition of luminescence of E. coli lum + have a stimulating effect. There is evidence that effect of inhibition of the luminescence of the control culture is dose-dependent.Conclusion. The results of a comparative examination of the bacterial action profile of the native exometabolites complex and Actoflor-S preparation confirm the presence of combination of the necessary inhibitory and stimulating activity against various agents of the microbiota. Creation of the metabiotics line based on Actoflor-S preparation with variability of biological properties and specialized for the management of various dysbiotic conditions show promise. An additional inclusion of native exometabolites of bifidobacteria and/or lactobacilli into the formula of artificial compositions will make it possible to expand the spectrum of the positive effect of probiotic preparations on the microorganism.

Contemporary information on biology of Akkermansia muciniphila and the role of these gut mucolytic anaerobic bacteria in physiological functions, metabolic and signaling reactions in human health and diseases are presented in the review. Established by foreign researchers, favorable and negative effects are associated with the presence in these gram-negative bacteria specific surface membrane proteins, the production of certain short-chain fatty acids and endotoxin, as well as with the ability degrading mucin, changing intestinal barrier function and synthesizing some neurotransmitters. Prospects and difficulties of creation of new microbial nutraceuticals and drugs on the basis of living cells of A. muciniphila or their specific low-molecular components and metabolites are considered.

The Arctic is currently a strategic region of Russia and it requires military protection. Good nutrition is a prerequisite for successful performance of the servicemen in such extreme conditions. The Russian armed forces do not have a special ration for the Arctic region. The existing rations lack products enriched with biologically ac- tive substances, probiotics, prebiotics, or vitamin and mineral complexes. Subcaloric nutrition, even with short-term physical exertion, in combination with low temperatures deprives the human body of vitamins and minerals. There- fore, the development of freeze-dried bioproducts with functional properties is highly relevant. This article presents the results of a study aimed to develop new freeze-dried milk-based bioproducts for the Russian military in the Arc- tic. For this, we created a microbial consortium of lactic acid bacteria with a wide spectrum of antimicrobial activity. We also used a range of functional ingredients, namely pectin, pine nut meal, a ‘Lactobel’ prebiotic protein-and-car- bohydrate product, rowan puree, and rosehip syrup in the amounts established during the study. The new freeze- dried milk-based bioproducts named ‘Pobeda’, enriched with combiotics and metabiotics, will provide the Russian military with better nutrition in the extreme conditions of the Arctic.

Background and Objective: The cellular microenvironment, diet, and lifestyle play a key role in the occurrence of colorectal cancer. Due to its rising trend, attempts are being made to devise novel biointerventions as adjunct to conventional therapies to prevent this deadly disease. “Metabiotics,” the beneficial metabolic signatures of probiotics are emerging as potential anticancer agent due to their ability to alter metabolic processes in the gut lumen and reduce the severity of colon carcinogenesis. Although beneficial attributes of metabiotics have been elucidated in vitro, yet their anticancer mechanism in vivo needs to be explored. Thus, the present study was performed to envisage anticancer potential of metabiotic extract obtained from indigenous probiotic, Lactobacillus rhamnosus MD 14, in early experimental colon carcinogenesis.Materials and Methods: Sprague–Dawley rats were daily administered with low, medium, and high dose of metabiotic extract orally along with a single dose of weekly intraperitoneal injection of 1,2-dimethylhydrazine up to 6 weeks and monitored for the markers of early colon carcinogenesis.Results: It was observed that the medium dose of metabiotic extract attenuated early colon carcinogenesis by reducing fecal procarcinogenic enzymes, oxidants, aberrant crypt foci, vis-à-vis downregulating oncogenes [K-ras, β-catenin, Cox-2, nuclear factor kappa B (NF-κB)] and upregulating tumor suppressor p53 gene leading to almost normal colon histology.Conclusions: It can be suggested that metabiotics modulate experimental colorectal cancer and could be used as a promising alternative of probiotics, particularly in immunocompromised individuals.

The altered gut microbiome (dysbiosis) is involved in the pathogenesis of most non-infectious gastrointestinal diseases, such as inflammatory bowel disease (IBD), irritable bowel syndrome, colorectal cancer, celiac disease, hepatic encephalopathy, non-alcoholic fatty liver disease, alcoholic liver disease, cholelithiasis and others. The molecular aspects of the interaction between dysbiotic microbiota and host immune system are considered in the context of IBD pathogenesis. The authors do provide original interpretations of the concepts of taxonomic (microbiological) and metabolic (functional) dysbiosis. Special attention is paid to the hypothesis that gut dysbiosis is caused not so much by structural changes in the microbiome as by alterations in microbial metabolism. Thus, the metabolome is a greater predictor of dysbiosis, than the taxonomic composition of the microbiome. It is important to consider dysbiotic changes in the gut microbiota in patients with ulcerative colitis and Crohn's disease, since they may significantly affect the course and prognosis of IBD. Factors hampering the microbiota assessment in clinical practice are discussed in detail, and advanced dysbiosis tests, including the GA-map Dysbiosis Test (GA-test) and the Colonoflor-16 Test, are described. By means of clinical studies it is demonstrated that a reduction in the genetic capacity of the microbiome for butyrate synthesis, together with an increase in pathobionts and a decrease in microbial diversity, is an important and necessary feature of dysbiosis in IBD patients. Thus, the butyryl-CoA:acetate CoA-transferase (BCoAT) gene level can be considered as a valuable biomarker to assess gut microbiota function in clinical practice. In conclusion, approaches to correct gut dysbiosis using probiotics, prebiotics, metabiotics and fecal microbiota transplantation as an addition to conventional treatment in IBD are critically discussed.

The effectiveness of regeneration is provided by normal over exchange and regulatory responses, so the regenerative therapy should be directed at identifying and addressing the causes of dismetabolk influences. Mikrobiocenosis is an integral part of holistic human organism takes part in realization of all metabolic reactions of the media. Correction of disbiosis helps restore regenerative processes, for the development of this direction is necessary to develop a new generation of probiotic preparations.

Background and Objective: The cellular microenvironment, diet, and lifestyle play a key role in the occurrence of colorectal cancer. Due to its rising trend, attempts are being made to devise novel biointerventions as adjunct to conventional therapies to prevent this deadly disease. "Metabiotics," the beneficial metabolic signatures of probiotics are emerging as potential anticancer agent due to their ability to alter metabolic processes in the gut lumen and reduce the severity of colon carcinogenesis. Although beneficial attributes of metabiotics have been elucidated in vitro , yet their anticancer mechanism in vivo needs to be explored. Thus, the present study was performed to envisage anticancer potential of metabiotic extract obtained from indigenous probiotic, Lactobacillus rhamnosus MD 14, in early experimental colon carcinogenesis. Materials and Methods: Sprague–Dawley rats were daily administered with low, medium, and high dose of metabiotic extract orally along with a single dose of weekly intraperitoneal injection of 1,2-dimethylhydrazine up to 6 weeks and monitored for the markers of early colon carcinogenesis. Results: It was observed that the medium dose of metabiotic extract attenuated early colon carcinogenesis by reducing fecal procarcinogenic enzymes, oxidants, aberrant crypt foci, vis-à-vis downregulating oncogenes [K-ras, β-catenin, Cox-2, nuclear factor kappa B (NF-κB)] and upregulating tumor suppressor p53 gene leading to almost normal colon histology. Conclusions: It can be suggested that metabiotics modulate experimental colorectal cancer and could be used as a promising alternative of probiotics, particularly in immunocompromised individuals. [ABSTRACT FROM AUTHOR]

Recently, the term metabiotics has emerged as a new concept of probiotics. This concept entails combining existing probiotic components with metabolic by-products improve specific physiological functionalities. Representative ingredients of these metabiotics include short-chain fatty acids (SCFAs), bacteriocins, polysaccharides, and peptides. The new concept is highly regarded as it complements the side effects of existing probiotics and is safe and easy to administer. Known health functions of metabiotics are mainly immune regulation, anti-inflammatory, anticancer, and brain-neurological health. Research has been actively conducted on the health benefits related to the composition of intestinal microorganisms. Among them, the focus has been on brain neurological health, which requires extensive research. This study showed that neurological disorders, such as depression, anxiety, autism spectrum disorder, Alzheimer's disease, and Parkinson's disease, can be treated and prevented according to the gut-brain axis theory by changing the intestinal microflora. In addition, various studies are being conducted on the immunomodulatory and anticancer effects of substances related to metabiotics of the microbiome. In particular, its efficacy is expected to be confirmed through human studies on various cancers. Therefore, developing various health functional effects of the next-generation probiotics such as metabiotics to prevent or treatment of various diseases is anticipated.

Gut microbiota is an important modulator of human health and contributes to high inter-individual variation in response to food and pharmaceutical ingredients. The clinical outcomes of interventions with prebiotics, probiotics, and synbiotics have been mixed and often unpredictable, arguing for novel approaches for developing microbiome-targeted therapeutics. Here, we review how the gut microbiota determines the fate of and individual responses to dietary and xenobiotic compounds via its immense metabolic potential. We highlight that microbial metabolites play a crucial role as targetable mediators in the microbiota-host health relationship. With this in mind, we expand the concept of synbiotics beyond prebiotics' role in facilitating growth and engraftment of probiotics, by focusing on microbial metabolism as a vital mode of action thereof. Consequently, we discuss synbiotic compositions that enable the guided metabolism of dietary or co-formulated ingredients by specific microbes leading to target molecules with beneficial functions. A workflow to develop novel synbiotics is presented, including the selection of promising target metabolites (e.g. equol, urolithin A, spermidine, indole-3 derivatives), identification of suitable substrates and producer strains applying bioinformatic tools, gut models, and eventually human trials.In conclusion, we propose that discovering and enabling specific substrate-microbe interactions is a valuable strategy to rationally design synbiotics that could establish a new category of hybrid nutra-/pharmaceuticals.

The purpose of this work is to review data on the biological effectiveness of probiotics, their mechanisms of action, and the prospects for the development of new-generation preparations. Scientific and practical justification of symbiotic drugs of a new generation – metabiotics as a continuation of the probiotic concept is given. The authors discuss the literature data and their own results, which allow them to propose new approaches to the creation of symbiotic drugs. The authors scientifically substantiate the main scientific provisions of the probiotic concept for the development of new-generation symbiotic drugs: study of aspects of the cultivation of the metabolic probiotic B. bifidum strain No. 1 in appropriate nutrient media; determination of the quantitative and qualitative composition of metabolites in the probiotic producer; scientific and practical substantiation of the qualitative and quantitative composition of the experimental probiotic suspension as a biologically active additive; the effect of probiotic suspension on the metabolism, the formation of microbiocenosis and nonspecific immunity. The substantiation for the creation of new feed probiotic preparations in the form of a composition of living microorganisms with molasses-based metabolites is given, which has a certain scientific and practical significance, and is promising for use in animal diets. Studies have found that to stabilize normal microflora in suckling pigs and weanlings, it is advisable to use various drugs in the form of biologically active additives of probiotic agents and their metabolites. The article provides a scientific and practical justification of a dietary supplement for correcting the microbiocenosis of the gastrointestinal tract and some factors of cellular immunity in growing young pigs based on the probiotic microorganism B. bifidum when cultivated on a nutrient medium from molasses.

The authors discuss the theory of human superorganism and its microbiota (microbiome), whose mutualistic interactions is realized within the microbiota – gut – brain axis that includes endocrine, immune and neurohumoral pathways. The newest concepts of microbiome enterotypes and core microbiota are presented, which are important for understanding of the role of symbiotic microorganisms in human vital activities, for explanation of pathophysiology of many chronic human diseases (beyond gastrointestinal disorders), as well as for the search of effective therapeutic targets. As highly promising are considered the functional approaches to studies of microbiota that allowed to formulate the concept of phylometabolic (phylofunctional) core. This is a series of evolutionally stable microorganisms responsible for majority of the main microbiome functions, such as fermentation of polysaccharides (glycans), production of short-chain fatty acids (butyrate, propionate, acetate), hydrogen utilization, production of lactate, metabolism of aminoacids, bile acids, choline, production of vitamins and some biologically active substances – anti-inflammatory, anti-microbial, immunostimulatory. The authors are first to describe the main functional groups of microorganisms of gut microbiota phylometabolic core, providing key metabolic functions, as well as the leading characteristics of the phylometabolic core as such. The perspectives of modification of composition and functions of phylometabolic microbiota core are discussed based on metabiotics as a virtually new class of therapeutic agents. A hypothesis has been proposed that the ratios between main components of the key gut microbiota may reflect fundamental processed related to a mutualistic interactions between microbiota and human body, as well as they may serve as effective biological markers of dysbiotic states determining the development of various pathologic conditions. For example, the ratio between Bacteroides spp. and butyrate producing bacteria that indirectly indicates total numbers of microbial genes can be used both for assessment of chronic inflammation of various localization (starting from inflammatory bowel disease to fat tissue inflammation related to metabolic syndrome), and for control of treatment efficacy.

Based on the evaluation of the composition and functions of the intestinal microflora and mechanism for the realization of "microflora - macroorganism" relationship, as well as causes of intestinal micro-ecological disorders, the need and options for their timely correction are demonstrated. The main principles of treatment and preventive actions are presented. Taking into account recent classifications and requirements for drugs, as well as evaluation of the mechanism of action and therapeutic options, the main groups of drugs (pro-, prebiotics and metabiotics) used in the management of gut microbiota in disease are described.

Introduction: According to WHO, antibiotic resistance is increasing to hazardous levels worldwide. Candidiasis often occurs after taking antibiotics. Therefore, antibiotic resistance is a global problem and searching for antibacterial agents is necessary., Aim: To determine the antimicrobial activity of bacterial lysate of Lactobacillus (L.) rhamnosus DV separately and with plant extracts against bacterial and yeast test cultures., Material and Methods: Antimicrobial activity of Del-Immune V ® (cell wall and DNA fragments from a L. rhamnosus DV) separately and with cinnamon, beetroot, and blackcurrant extracts was determined by the minimum inhibitory concentration (MIC). Twofold serial dilutions determined the MIC in previously prepared meat-peptone broth (MPB) for bacteria and liquid wort for yeast. In the study, gram-negative ( Escherichia coli IEM-1, Proteus vulgaris PА-12, Pseudomonas sp. MI-2, L. rhamnosus 13/2) and gram-positive ( Bacillus (B.) subtilis BТ-2, Staphylococcus aureus BМС-1) bacteria, as well as yeast ( Candida (C.) albicans D-6, C. tropicalis PE-2, C. utilis BVS-65) were used as test cultures., Results: The MIC for the studied bacterial test cultures after application of L. rhamnosus DV bacterial lysates was from 1.0 ± 0.05 mg/mL to 12.5 ± 0.63 mg/mL, which was significantly less than that of the thermally inactivated control (MIC from 125.0 ± 6.25 mg/mL to 250.0 ± 12.5 mg/mL). B. subtilis BT-2 culture was the least sensitive to the action of the bacterial lysate (MIC-12.5 ± 0.63 mg/mL). It showed the best antibacterial and antifungal effect bacterial lysate with the phytonutrient blackcurrant., Conclusions: It was demonstrated that bacterial lysate of lactic acid bacteria L. rhamnosus DV exhibits antibacterial and antifungal properties during direct contact with pathogenic agents., Competing Interests: Author FG is employed by MirImmunoPharm LLC, Kyiv, Ukraine The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Penchuk, Savytska, Kobyliak, Ostapchenko, Kolodiy, Onysenko, Tsyryuk, Korotkyi, Grygoriev and Falalyeyeva.)

Colorectal cancer is closely associated with environment, diet and lifestyle. Normally it is treated with surgery, radiotherapy or chemotherapy but increasing systemic toxicity, resistance and recurrence is prompting scientists to devise new potent and safer alternate prophylactic or therapeutic strategies. Among these, probiotics, prebiotics, synbiotics and metabiotics are being considered as the promising candidates. Metabiotics or probiotic derived factors can optimize various physiological functions of the host and offer an additional advantage to be utilized even in immunosuppressed individuals. Interestingly, anti colon cancer potential of probiotic strains has been attributable to metabiotics that have epigenetic, antimutagenic, immunomodulatory, apoptotic and antimetastatic effects. Thus, it’s time to move one step further to utilize metabiotics more smartly by avoiding the risks associated with probiotics even in certain normal / or immuno compromised host. Here an attempt is made to provide insight into the adverse effects associated with probiotics and beneficial aspects of metabiotics with main emphasis on the modulatory mechanisms involved in colon cancer.

Colorectal cancer is closely associated with environment, diet and lifestyle. Normally it is treated with surgery, radiotherapy or chemotherapy but increasing systemic toxicity, resistance and recurrence is prompting scientists to devise new potent and safer alternate prophylactic or therapeutic strategies. Among these, probiotics, prebiotics, synbiotics, and metabiotics are being considered as the promising candidates. Metabiotics or probiotic derived factors can optimize various physiological functions of the host and offer an additional advantage to be utilized even in immunosuppressed individuals. Interestingly, anti colon cancer potential of probiotic strains has been attributable to metabiotics that have epigenetic, antimutagenic, immunomodulatory, apoptotic, and antimetastatic effects. Thus, it's time to move one step further to utilize metabiotics more smartly by avoiding the risks associated with probiotics even in certain normal/or immuno compromised host. Here, an attempt is made to provide insight into the adverse effects associated with probiotics and beneficial aspects of metabiotics with main emphasis on the modulatory mechanisms involved in colon cancer. [ABSTRACT FROM AUTHOR]

Wild probiotic consortia of microorganisms (bacteria and yeasts) associated in the artisanal cultures' microbiota (milk kefir grains, water kefir grains and kombucha) are considered valuable promoters for metabiotics (prebiotics, probiotics, postbiotics and paraprobiotics) production. The beneficial effects of the fermented products obtained with the artisanal cultures on human well-being are described by centuries and the interest for them is continuously increasing. The wild origin and microbial diversity of these above-mentioned consortia give them extraordinary protection capacity against microbiological contaminants in unusual physico-chemical conditions and unique fermentative behaviour. This review summarizes the state of the art for the wild artisanal cultures (milk and water kefir grains, respectively, kombucha—SCOBY), their symbiotic functionality, and the ability to ferment unconventional substrates in order to obtain valuable bioactive compounds with in vitro and in vivo beneficial functional properties. Due to the necessity of the bioactives production and their use as metabiotics in the modern consumer's life, artisanal cultures are the perfect sources able to biosynthesize complex functional metabolites (bioactive peptides, antimicrobials, polysaccharides, enzymes, vitamins, cell wall components). Depending on the purposes of the biotechnological fermentation processes, artisanal cultures can be used as starters on different substrates. Current studies show that the microbial synergy between bacteria—yeast and/or bacteria—offers new perspectives to develop functional products (food, feeds, and ingredients) with a great impact on life quality. [ABSTRACT FROM AUTHOR]