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Prebiotics and Probiotics: Healthy Biotools for Molecular Integrative and Modulation Approaches 2.0

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (10 December 2023) | Viewed by 12981

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Prof. Dr. Abdelali Daddaoua

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1. Department of Biochemistry and Molecular Biology II, Faculty of Pharmacy, University of Granada, 18011 Granada, Spain
2. Instituto de Investigación Biosanitaria (IBS), 18014 Granada, Spain
3. Institute of Nutrition and Food Technology “José Mataix”, Center of Biomedical Research, University of Granada, Avda. del Conocimiento s/n. Armilla, 18016 Granada, Spain
Interests: nutrition and dietetics nutritional; biochemistry; pharmacy; cell biology; molecular biology; immunology; regulation of the gene expression in prokaryotes and eukaryotes; pathogens; enzymology and biotechnology
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Prof. Dr. Margarita Aguilera

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1. Department of Microbiology, Faculty of Pharmacy, University of Granada, 18011 Granada, Spain
2. Instituto de Investigación Biosanitaria (IBS), 18014 Granada, Spain
3. Institute of Nutrition and Food Technology “José Mataix”, Center of Biomedical Research, University of Granada, Avda. del Conocimiento s/n. Armilla, 18016 Granada, Spain
Interests: probiotics; next-generation probiotics; molecular microbiology; microbiome; culturomics and toxicomicrobiomics
Special Issues, Collections and Topics in MDPI journals

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Dear Colleagues,

The key role played by beneficial bacteria at the intestine through promoting overall human health is generally accepted. Helpful bacteria in the colon have many important functions that include increasing mineral homeostasis, strengthening the intestinal barrier, regulating the immune response and therefore human health and wellbeing. Hence, probiotics and prebiotics are food bioproducts that exert key functions in maintaining human gut eubiosis and are specially designed for this purpose.

After decades of basic and clinical research, together with the evolution of biotechnological and high-throughput technologies, a huge impact on understanding the effect of probiotics, prebiotics on the immune response, and antibacterial infection have been achieved. Thus, these biotools have become the main instruments to intervene and optimize several physiological functions of the microbiota. Moreover, considerable efforts have been made to influence the intestinal microbiota by dietary complementary means in such a way that the health of the host is positively affected.

Functional foods are those which provide benefits beyond their traditional nutritional value, either enhancing a function of the body or reducing the risk of a disease. One of the main types of functional foods are prebiotics, which are non-digestible foods (mostly oligosaccharides) that selectively stimulate the growth of a limited number of host-friendly colonic bacteria. From a chemical standpoint, resistance to human digestive enzymes and low absorption are key for these compounds to reach the distal parts of the gut, where they can be fermented by the microbiota, which in turn is selectively modified in the process. It is important to note that pathological alterations of the intestinal microbiota (dysbiosis) have been related to conditions such as obesity, diabetes, and fatty liver, and of course in inflammatory bowel disease and infection with pathogenic bacteria.

It is clear that the diversity of prebiotic substances, probiotic microbes, and the influences that they may respectively exert mean that any health-enhancement claims must be supported by experimental and clinical data. However, the molecular mechanisms and interactions of prebiotics and probiotics with their specific targets for immune responses are not well known, and such information will help to identify new alternative compounds as therapies against various pathologies.

The goal of this Special Issue is to further expand our knowledge of the molecular mechanism of prebiotics and probiotics, as well as to offer a complete and broad view of the current situation in the area, and its future projection, pointing out the new indications that will enrich this field.

In this Special Issue, we welcome innovative and original research articles, as well as high-quality review articles with pioneering opinions with a focus on probiotics and prebiotics and balance host health/disease, related to their antibacterial roles.

Prof. Dr. Abdelali Daddaoua
Prof. Dr. Margarita Aguilera
Guest Editors

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Prebiotics and Probiotics: Healthy Biotools for Molecular Integrative and Modulation Approaches in International Journal of Molecular Sciences (11 articles)

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14 pages, 3658 KiB

Open AccessArticle

Probiotic-Induced Modulation of Microbiota Composition and Antibiotic Resistance Genes Load, an In Vitro Assessment

by Alicja Maria Nogacka, Silvia Saturio, Guadalupe Monserrat Alvarado-Jasso, Nuria Salazar, Clara G. de los Reyes Gavilán, Ceferino Martínez-Faedo, Adolfo Suarez, Ruipeng Wang, Kenji Miyazawa, Gaku Harata, Akihito Endo, Silvia Arboleya and Miguel Gueimonde

Int. J. Mol. Sci. 2024, 25(2), 1003; https://doi.org/10.3390/ijms25021003 - 13 Jan 2024

Viewed by 803

Abstract

The imbalance of the gut microbiota (GM) is known as dysbiosis and is associated with disorders such as obesity. The increasing prevalence of microorganisms harboring antibiotic resistance genes (ARG) in the GM has been reported as a potential risk for spreading multi-drug-resistant pathogens. The objective of this work was the evaluation, in a fecal culture model, of different probiotics for their ability to modulate GM composition and ARG levels on two population groups, extremely obese (OB) and normal-weight (NW) subjects. Clear differences in the basal microbiota composition were observed between NW and OB donors. The microbial profile assessed by metataxonomics revealed the broader impact of probiotics on the OB microbiota composition. Also, supplementation with probiotics promoted significant reductions in the absolute levels of tetM and tetO genes. Regarding the blaTEM gene, a minor but significant decrease in both donor groups was detected after probiotic addition. A negative association between the abundance of Bifidobacteriaceae and the tetM gene was observed. Our results show the ability of some of the tested strains to modulate GM. Moreover, the results suggest the potential application of probiotics for reducing the levels of ARG, which constitutes an interesting target for the future development of probiotics. Full article

(This article belongs to the Special Issue Prebiotics and Probiotics: Healthy Biotools for Molecular Integrative and Modulation Approaches 2.0)

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11 pages, 873 KiB

Open AccessArticle

How Do Prebiotics Affect Human Intestinal Bacteria?—Assessment of Bacterial Growth with Inulin and XOS In Vitro

by Nelly Schropp, Virginie Stanislas, Karin B. Michels and Kerstin Thriene

Int. J. Mol. Sci. 2023, 24(16), 12796; https://doi.org/10.3390/ijms241612796 - 14 Aug 2023

Cited by 1 | Viewed by 1327

Abstract

Prebiotics are believed to exhibit high specificity in stimulating the growth or activity of a limited number of commensal microorganisms, thereby conferring health benefits to the host. However, the mechanism of action of prebiotics depends on multiple factors, including the composition of an individual’s gut microbiota, and is therefore difficult to predict. It is known that different bacteria can utilize inulin and xylooligosaccharides (XOS), but an overview of which bacteria in the human gut may be affected is lacking. Detailed knowledge of how bacterial growth is affected by prebiotics is furthermore useful for the development of new synbiotics, which combine a living microorganism with a selective substrate to confer a health benefit to the host. Hence, we developed a statistical model to compare growth in vitro among typical human gut bacteria from different phylogenetic lineages. Based on continuous observation of the optical density (OD₆₀₀), we compare maximal growth rates (r_max), maximal attained OD₆₀₀ (OD_max), and area under the growth curve (AUC) of bacteria grown on inulin or XOS. The consideration of these three parameters suggests strain-specific preferences for inulin or XOS and reveals previously unknown preferences such as Streptococcus salivarius growth on XOS. Full article

(This article belongs to the Special Issue Prebiotics and Probiotics: Healthy Biotools for Molecular Integrative and Modulation Approaches 2.0)

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21 pages, 3903 KiB

Open AccessArticle

Bacteriocin-Producing Escherichia coli Q5 and C41 with Potential Probiotic Properties: In Silico, In Vitro, and In Vivo Studies

by Veronika S. Mihailovskaya, Dmitry A. Sutormin, Marina O. Karipova, Anna B. Trofimova, Victor A. Mamontov, Konstantin Severinov and Marina V. Kuznetsova

Int. J. Mol. Sci. 2023, 24(16), 12636; https://doi.org/10.3390/ijms241612636 - 10 Aug 2023

Viewed by 1608

Abstract

Commensal bacteriocin-producing Escherichia coli are of interest for possible use as probiotics to selectively control the spread of pathogenic bacteria. Here, we evaluated the biosafety and efficacy of two new bacteriocin-producing E. coli strains, Q5 (VKM B-3706D) and C41 (VKM B-3707D), isolated from healthy farm animals. The genomes of both strains were sequenced, and genes responsible for the antagonistic and colonization abilities of each strain were identified. In vitro studies have shown that both strains were medium-adhesive and demonstrated antagonistic activity against most enteropathogens tested. Oral administration of 5 × 10⁸ to 5 × 10¹⁰ colony-forming units of both strains to rats with drinking water did not cause any disease symptoms or side effects. Short-term (5 days) oral administration of both strains protected rats from colonization and pathogenic effects of a toxigenic beta-lactam-resistant strain of E. coli C55 and helped preserve intestinal homeostasis. Taken together, these in silico, in vitro, and in vivo data indicate that both strains (and especially E. coli Q5) can be potentially used for the prevention of colibacillosis in farm animals. Full article

(This article belongs to the Special Issue Prebiotics and Probiotics: Healthy Biotools for Molecular Integrative and Modulation Approaches 2.0)

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17 pages, 4046 KiB

Open AccessArticle

Anti-Cancer Roles of Probiotic-Derived P8 Protein in Colorectal Cancer Cell Line DLD-1

by Byung Chull An, Jun Young Ahn, Daebeom Kwon, Sang Hee Kwak, Jin Young Heo, Seungwoo Kim, Yongku Ryu and Myung Jun Chung

Int. J. Mol. Sci. 2023, 24(12), 9857; https://doi.org/10.3390/ijms24129857 - 07 Jun 2023

Cited by 4 | Viewed by 1628

Abstract

A novel probiotics-derived protein, P8, suppresses the growth of colorectal cancer (CRC). P8 can penetrate the cell membrane via endocytosis and cause cell cycle arrest in DLD-1 cells through down-regulation of CDK1/Cyclin B1. However, neither the protein involved in the endocytosis of P8 nor the cell cycle arrest targets of P8 are known. We identified two P8-interacting target proteins [importin subunit alpha-4 (KPNA3) and glycogen synthase kinase-3 beta (GSK3β)] using P8 as a bait in pull-down assays of DLD-1 cell lysates. Endocytosed P8 in the cytosol was found to bind specifically to GSK3β, preventing its inactivation by protein kinases AKT/CK1ε/PKA. The subsequent activation of GSK3β led to strong phosphorylation (S^33,37/T⁴¹) of β-catenin, resulting in its subsequent degradation. P8 in the cytosol was also found to be translocated into the nucleus by KPNA3 and importin. In the nucleus, after its release, P8 binds directly to the intron regions of the GSK3β gene, leading to dysregulation of GSK3β transcription. GSK3β is a key protein kinase in Wnt signaling, which controls cell proliferation during CRC development. P8 can result in a cell cycle arrest morphology in CRC cells, even when they are in the Wnt ON signaling state. Full article

(This article belongs to the Special Issue Prebiotics and Probiotics: Healthy Biotools for Molecular Integrative and Modulation Approaches 2.0)

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22 pages, 6106 KiB

Open AccessArticle

Dietary Supplementation of Inulin Contributes to the Prevention of Estrogen Receptor-Negative Mammary Cancer by Alteration of Gut Microbial Communities and Epigenetic Regulations

by Huixin Wu, William J. Van Der Pol, Laura G. Dubois, Casey D. Morrow and Trygve O. Tollefsbol

Int. J. Mol. Sci. 2023, 24(10), 9015; https://doi.org/10.3390/ijms24109015 - 19 May 2023

Cited by 3 | Viewed by 2217

Abstract

Breast cancer (BC) is among the most frequently diagnosed malignant cancers in women in the United States. Diet and nutrition supplementation are closely related to BC onset and progression, and inulin is commercially available as a health supplement to improve gut health. However, little is known with respect to inulin intake for BC prevention. We investigated the effect of an inulin-supplemented diet on the prevention of estrogen receptor-negative mammary carcinoma in a transgenic mouse model. Plasma short-chain fatty acids were measured, the gut microbial composition was analyzed, and the expression of proteins related to cell cycle and epigenetics-related genes was measured. Inulin supplementation greatly inhibited tumor growth and significantly delayed tumor latency. The mice that consumed inulin had a distinct microbiome and higher diversity of gut microbial composition compared to the control. The concentration of propionic acid in plasma was significantly higher in the inulin-supplemented group. The protein expression of epigenetic-modulating histone deacetylase 2 (Hdac2), Hdac8, and DNA methyltransferase 3b decreased. The protein expression of factors related to tumor cell proliferation and survival, such as Akt, phospho-PI3K, and NF-kB, also decreased with inulin administration. Furthermore, sodium propionate showed BC prevention effect in vivo through epigenetic regulations. These studies suggest that modulating microbial composition through inulin consumption may be a promising strategy for BC prevention. Full article

(This article belongs to the Special Issue Prebiotics and Probiotics: Healthy Biotools for Molecular Integrative and Modulation Approaches 2.0)

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20 pages, 2423 KiB

Open AccessArticle

Innova 2020: A Follow-Up Study of the Fecal Microbiota of Infants Using a Novel Infant Formula between 6 Months and 12 Months of Age

by Julio Plaza-Diaz, Francisco Javier Ruiz-Ojeda, Javier Morales, Rafael Martín-Masot, Eric Climent, Ángela Silva, Juan F. Martinez-Blanch, María Enrique, Marta Tortajada, Daniel Ramon, Beatriz Alvarez, Empar Chenoll and Ángel Gil

Int. J. Mol. Sci. 2023, 24(8), 7392; https://doi.org/10.3390/ijms24087392 - 17 Apr 2023

Cited by 1 | Viewed by 1706

Abstract

The World Health Organization recommends exclusive breastfeeding on demand until at least the sixth month of life. Breast milk or infant formula is the infant’s primary food source until the age of one year, followed by the gradual introduction of other foods. During weaning, the intestinal microbiota evolves to a profile close to that of the adult, and its disruption can result in an increased incidence of acute infectious diseases. We aimed to determine whether a novel starting formula (INN) provides gut microbiota compositions more similar to those of breastfed (BF) infants from 6 to 12 months of age compared to a standard formula (STD). This study included 210 infants (70 per group) who completed the intervention until they reached the age of 12 months. In the intervention period, infants were divided into three groups. Group 1 received an INN formula with a lower protein content, a casein to whey protein ratio of approximately 70/30, twice as much docosahexaenoic acid as the STD formula, a thermally inactivated postbiotic (Bifidobacterium animalis subsp. lactis, BPL1^TM HT), and twice as much arachidonic acid as the STD formula contained. The second group received the STD formula, while the third group was exclusively BF for exploratory purposes. In the course of the study, visits were conducted at 6 months and 12 months of age. Compared to the BF and STD groups, the Bacillota phylum levels in the INN group were significantly reduced after 6 months. At the end of 6 months, the alpha diversity indices of the BF and INN groups differed significantly from those of the STD group. At 12 months, the Verrucomicrobiota phylum levels in the STD group were significantly lower than those in the BF and INN groups. Based on the comparison between 6 and 12 months, the Bacteroidota phylum levels in the BF group were significantly higher than those in the INN and STD groups. When comparing the INN group with the BF and STD groups, Clostridium sensu stricto 1 was significantly higher in the INN group. The STD group had higher levels of calprotectin than the INN and BF groups at 6 months. The immunoglobulin A levels in the STD group were significantly lower than those in the INN and BF groups after 6 months. Both formulas had significantly higher levels of propionic acid than the BF group at 6 months. At 6 months, the STD group showed a higher quantification of all metabolic pathways than the BF group. The INN formula group exhibited similar behavior to the BF group, except for the superpathway of phospholipid biosynthesis (E. coli). We hypothesize that the novel INN formula may promote an intestinal microbiota that is more similar to the microbiota of an infant who consumes only human milk before the weaning period. Full article

(This article belongs to the Special Issue Prebiotics and Probiotics: Healthy Biotools for Molecular Integrative and Modulation Approaches 2.0)

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Review

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22 pages, 537 KiB

Open AccessReview

Lactiplantibacillus (Lactobacillus) plantarum as a Complementary Treatment to Improve Symptomatology in Neurodegenerative Disease: A Systematic Review of Open Access Literature

by Ana Isabel Beltrán-Velasco, Manuel Reiriz, Sara Uceda and Víctor Echeverry-Alzate

Int. J. Mol. Sci. 2024, 25(5), 3010; https://doi.org/10.3390/ijms25053010 - 05 Mar 2024

Viewed by 1152

Abstract

This systematic review addresses the use of Lactiplantibacillus (Lactobacillus) plantarum in the symptomatological intervention of neurodegenerative disease. The existence of gut microbiota dysbiosis has been associated with systemic inflammatory processes present in neurodegenerative disease, creating the opportunity for new treatment strategies. This involves modifying the strains that constitute the gut microbiota to enhance synaptic function through the gut–brain axis. Recent studies have evaluated the beneficial effects of the use of Lactiplantibacillus plantarum on motor and cognitive symptomatology, alone or in combination. This systematic review includes 20 research articles (n = 3 in human and n = 17 in animal models). The main result of this research was that the use of Lactiplantibacillus plantarum alone or in combination produced improvements in symptomatology related to neurodegenerative disease. However, one of the studies included reported negative effects after the administration of Lactiplantibacillus plantarum. This systematic review provides current and relevant information about the use of this probiotic in pathologies that present neurodegenerative processes such as Alzheimer’s disease, Parkinson’s disease and Multiple Sclerosis. Full article

(This article belongs to the Special Issue Prebiotics and Probiotics: Healthy Biotools for Molecular Integrative and Modulation Approaches 2.0)

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16 pages, 1305 KiB

Open AccessReview

Prebiotics and Probiotics: Therapeutic Tools for Nonalcoholic Fatty Liver Disease

by Alejandra Mijangos-Trejo, Natalia Nuño-Lambarri, Varenka Barbero-Becerra, Misael Uribe-Esquivel, Paulina Vidal-Cevallos and Norberto Chávez-Tapia

Int. J. Mol. Sci. 2023, 24(19), 14918; https://doi.org/10.3390/ijms241914918 - 05 Oct 2023

Cited by 2 | Viewed by 1720

Abstract

Alterations in the gut–liver axis and changes in the gut microbiome are among the risk factors for the pathogenesis of non-alcoholic fatty liver disease (NAFLD). These patients show increased bacterial overgrowth in the small intestine and impaired intestinal permeability. Therefore, therapeutic options such as probiotics or prebiotics have been investigated to modulate intestinal microbiota composition to improve NAFLD. Most in vivo and in vitro probiotic studies have focused on reducing hepatic fat accumulation. The beneficial effects of probiotics on NAFLD have been demonstrated in animal models, and the most widely used microorganisms are those of the Lactobacillus and Bifidobacterium genera. In animal models, probiotics help restore the intestinal microbiota and improve the integrity of the intestinal barrier. This narrative review summarizes published evidence and the likely benefits of probiotics and prebiotics as a therapeutic option for patients with NAFLD. Full article

(This article belongs to the Special Issue Prebiotics and Probiotics: Healthy Biotools for Molecular Integrative and Modulation Approaches 2.0)

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