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Parra I, Carrasco-Carballo A, Palafox-Sanchez V, Martínez-García I, Aguilera J, Góngora-Alfaro JL, Aranda-González II, Tizabi Y, Mendieta L. Peroxisome Proliferator-Activated Receptors (PPARs) May Mediate the Neuroactive Effects of Probiotic Metabolites: An In Silico Approach. Int J Mol Sci 2025; 26:4507. [PMID: 40429654 PMCID: PMC12111801 DOI: 10.3390/ijms26104507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Revised: 02/25/2025] [Accepted: 03/04/2025] [Indexed: 05/29/2025] Open
Abstract
It is well established that the gut-brain axis (GBA) is a bidirectional communication between the gut and the brain. This axis, critical in maintaining overall homeostasis, is regulated at the neuronal, endocrine, and immunological levels, all of which may be influenced by the gut microbiota (GM). Therefore, dysbiosis or disruption in the GM may have serious consequences including neuroinflammation due to overactivation of the immune system. Strategies to reestablish GM integrity via use of probiotics are being pursued as novel therapeutic intervention in a variety of central and peripheral diseases. The mechanisms leading to dysbiosis or efficacy of probiotics, however, are not fully evident. Here, we performed computational analysis on two major probiotics, namely Lactobacillus Lacticaseibacillus rhamnosus GG (formerly named Lactobacillus rhamnosus, L. rhamnosus GG) and Bifidobacterium animalis spp. lactis (B. lactis or B. animalis) to not only shed some light on their mechanism(s) of action but also to identify potential molecular targets for novel probiotics. Using the PubMed web page and BioCyc Database Collection platform we specifically analyzed proteins affected by metabolites of these bacteria. Our results indicate that peroxisome proliferator-activated receptors (PPARs), nuclear receptor proteins that are involved in regulation of inflammation are key mediators of the neuroactive effect of probiotics.
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Affiliation(s)
- Irving Parra
- Laboratorio de Neuroquímica, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla 72592, Mexico; (I.P.); (I.M.-G.)
| | - Alan Carrasco-Carballo
- Laboratorio de Elucidación y Síntesis en Química Orgánica, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla 72592, Mexico;
| | - Victoria Palafox-Sanchez
- Institute for Obesity Research, Instituto Tecnológico y de Estudios Superiores de Monterrey, Monterrey 64700, Mexico;
| | - Isabel Martínez-García
- Laboratorio de Neuroquímica, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla 72592, Mexico; (I.P.); (I.M.-G.)
| | - José Aguilera
- Institut de Neurociències, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain;
| | - José L. Góngora-Alfaro
- Departamento de Neurociencias, Centro de Investigaciones Regionales “Dr. Hideyo Noguchi”, Universidad Autónoma de Yucatán, Avenida Itzáes No. 490 x 59, Mérida 97000, Mexico;
| | - Irma Isela Aranda-González
- Facultad de Medicina, Universidad Autónoma de Yucatán, Avenida Itzáes No. 498 x 59 y 59A, Mérida 97000, Mexico;
| | - Yousef Tizabi
- Department of Pharmacology, Howard University College of Medicine, Washington, DC 20059, USA;
| | - Liliana Mendieta
- Laboratorio de Neuroquímica, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla 72592, Mexico; (I.P.); (I.M.-G.)
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Sujaya IN, Mariyatun M, Hasan PN, Manurung NEP, Pramesi PC, Juffrie M, Utami T, Cahyanto MN, Yamamoto S, Takahashi T, Asahara T, Akiyama T, Rahayu ES. Randomized study of Lacticaseibacillus fermented milk in Indonesian elderly houses: Impact on gut microbiota and gut environment. World J Gastroenterol 2025; 31:104081. [PMID: 40182598 PMCID: PMC11962840 DOI: 10.3748/wjg.v31.i12.104081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 01/21/2025] [Accepted: 02/24/2025] [Indexed: 03/26/2025] Open
Abstract
BACKGROUND Health maintenance in elderly houses includes management of the gut microbiota and the environment. Lacticaseibacillus paracasei Shirota (LcS) is a probiotic strain that positively affects the human gut. However, the evidence of its effects on the Indonesian population remains limited. AIM To investigate the effect of LcS-fermented milk on the gut microbiota and environment of Indonesian elderly houses. METHODS This double-blind, randomized, placebo-controlled trial involved 112 participants from Indonesian elderly houses, spanning a 2-week baseline and 24-week treatment. Participants were randomly assigned to probiotic or placebo groups, consuming fermented milk with or without LcS (> 6.5 × 109 colony-forming units). Fecal samples were collected every three months. Gut microbiota analysis was performed using 16S rRNA gene sequencing and reverse transcription quantitative polymerase chain reaction, while gut environment was assessed by measuring fecal organic acids, amino acid metabolites, and stool frequency. RESULTS Analyses of 16S rRNA gene sequence data at the 3-month period revealed increased Bifidobacterium and Succinivibrio and decreased Rikenellaceae RC9 gut group in the probiotic group. These shifts were associated with significant differences in β-diversity metrics. The change in Bifidobacterium was confirmed by reverse transcription quantitative polymerase chain reaction, demonstrating higher abundance in the probiotic group than in the placebo group (8.5 ± 1.1 vs 8.0 ± 1.1, log10 bacterial cells/g; P = 0.044). At 6-month period, the differences in Succinivibrio and Rikenellaceae RC9 gut group persisted. The probiotic group showed higher butyrate levels than the placebo group at the 6-month period (5.04 ± 3.11 vs 3.95 ± 2.89, μmol/g; P = 0.048). The effect on amino acid metabolites and stool frequency was not significant. CONCLUSION Daily intake of LcS positively affects the gut microbiota and environment of people living in Indonesian elderly houses.
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Affiliation(s)
- I Nengah Sujaya
- School of Public Health, Faculty of Medicine, Udayana University, Denpasar 80230, Bali, Indonesia
| | - Mariyatun Mariyatun
- Center for Food and Nutrition Studies, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
- Center of Excellence for Research and Application on Integrated Probiotics Industry, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
| | - Pratama Nur Hasan
- Center for Food and Nutrition Studies, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
- Center of Excellence for Research and Application on Integrated Probiotics Industry, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
| | - Nancy Eka Putri Manurung
- Center for Food and Nutrition Studies, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
- Center of Excellence for Research and Application on Integrated Probiotics Industry, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
| | - Putrika Citta Pramesi
- Center for Food and Nutrition Studies, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
- Center of Excellence for Research and Application on Integrated Probiotics Industry, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
- Department of Food and Agricultural Product Technology, Faculty of Agricultural Technology, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
| | - Mohammad Juffrie
- Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
| | - Tyas Utami
- Center of Excellence for Research and Application on Integrated Probiotics Industry, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
- Department of Food and Agricultural Product Technology, Faculty of Agricultural Technology, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
| | - Muhammad Nur Cahyanto
- Department of Food and Agricultural Product Technology, Faculty of Agricultural Technology, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
| | - Shuta Yamamoto
- Yakult Central Institute, Yakult Honsha Co., Ltd., Kunitachi 186-8650, Tōkyō, Japan
| | - Takuya Takahashi
- Yakult Honsha European Research Center for Microbiology VOF, Ghent 9052, East Flanders, Belgium
| | - Takashi Asahara
- Yakult Central Institute, Yakult Honsha Co., Ltd., Kunitachi 186-8650, Tōkyō, Japan
| | - Takuya Akiyama
- Yakult Central Institute, Yakult Honsha Co., Ltd., Kunitachi 186-8650, Tōkyō, Japan
| | - Endang Sutriswati Rahayu
- Center for Food and Nutrition Studies, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
- Center of Excellence for Research and Application on Integrated Probiotics Industry, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
- Department of Food and Agricultural Product Technology, Faculty of Agricultural Technology, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
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Vinceković M, Živković L, Turkeyeva E, Mutaliyeva B, Madybekova G, Šegota S, Šijaković Vujičić N, Pustak A, Jurkin T, Kiš M, Kajić S. Development of Alginate Composite Microparticles for Encapsulation of Bifidobacterium animalis subsp. lactis. Gels 2024; 10:752. [PMID: 39590108 PMCID: PMC11593877 DOI: 10.3390/gels10110752] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Revised: 11/13/2024] [Accepted: 11/13/2024] [Indexed: 11/28/2024] Open
Abstract
The probiotic bacterium Bifidobacterium animalis subsp. lactis BB-12 (BB-12) was encapsulated in two composites, alginate/agar and alginate/agar/casein. The network structure and physicochemical properties of these composites are influenced by complex interactions, including hydrogen bonding, electrostatic forces between biopolymers, calcium ions, and the encapsulated bacteria. The composites demonstrated a granular surface, with the granules being spatially oriented on the alginate/agar/BB-12 surface and linearly oriented on the alginate/agar/casein/BB-12 surface. They possess a highly organized microparticle structure and exhibit viscoelastic solid-like behavior. The alginate/agar/BB-12 composite showed higher storage modulus, shear stress, and shear strain values, indicating enhanced stability in various physical environments. Both composites displayed good thermal stability, aligning with their rheological properties, confirming their well-ordered structures. Despite differences in composite structures, the release mechanism of bacteria is governed by Fickian diffusion through the composite matrix. Based on physicochemical properties, the alginate/agar/casein composite is recommended for dairy product fermentation, while the alginate/agar composite seems more suitable for oral use. These findings provide new insights into the interactions between bacterial cultures and alginate composite ingredients.
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Affiliation(s)
- Marko Vinceković
- Division of Agroecology, Department of Chemistry, University of Zagreb Faculty of Agriculture, Svetošimunska 25, 10000 Zagreb, Croatia;
| | - Lana Živković
- Division of Agroecology, Department of Chemistry, University of Zagreb Faculty of Agriculture, Svetošimunska 25, 10000 Zagreb, Croatia;
| | - Elmira Turkeyeva
- Biotechnology Department, M. Auezov South-Kazakhstan University, Tauke-Khan, Shymkent 160000, Kazakhstan; (E.T.); (B.M.)
| | - Botagoz Mutaliyeva
- Biotechnology Department, M. Auezov South-Kazakhstan University, Tauke-Khan, Shymkent 160000, Kazakhstan; (E.T.); (B.M.)
| | - Galiya Madybekova
- Chemistry Department, O. Zhanibekov South-Kazakhstan Pedagogical University, Baitursynov Street, 13, Shymkent 160000, Kazakhstan;
| | - Suzana Šegota
- Laboratory for Biocolloids and Surface Chemistry, Ruđer Bošković Institute, Bijenička c. 54, 10000 Zagreb, Croatia;
| | - Nataša Šijaković Vujičić
- Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička c. 54, 10000 Zagreb, Croatia;
| | - Anđela Pustak
- Radiation Chemistry and Dosimetry Laboratory, Ruđer Bošković Institute, Bijenička c. 54, 10000 Zagreb, Croatia; (A.P.); (T.J.)
| | - Tanja Jurkin
- Radiation Chemistry and Dosimetry Laboratory, Ruđer Bošković Institute, Bijenička c. 54, 10000 Zagreb, Croatia; (A.P.); (T.J.)
| | - Marta Kiš
- Faculty of Veterinary Medicine, University of Zagreb, Ul. Vjekoslava Heinzela 55, 10000 Zagreb, Croatia
| | - Sanja Kajić
- Division of Agroecology, Department of Microbiology, University of Zagreb Faculty of Agriculture, 10000 Zagreb, Croatia
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Zhou L, Yin X, Fang B, He J, Zhan J, Zhang X, Wang R. Effects of Bifidobacterium animalis subsp. lactis IU100 on Immunomodulation and Gut Microbiota in Immunosuppressed Mice. Microorganisms 2024; 12:493. [PMID: 38543544 PMCID: PMC10972214 DOI: 10.3390/microorganisms12030493] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Revised: 02/24/2024] [Accepted: 02/28/2024] [Indexed: 08/22/2024] Open
Abstract
Probiotics are live microorganisms with immunomodulatory effects in a strain-specific and dose-dependent manner. Bifidobacterium animalis subsp. lactis IU100 is a new probiotic strain isolated from healthy adults. This study aimed to evaluate the effects of IU100 on cyclophosphamide (CTX)-induced immunosuppression in mice. The results showed that IU100 significantly ameliorated CTX-induced decreases in body weight and immune organ indices. The promoted delayed-type hypersensitivity, serum hemolysins and immunoglobulin (IgA, IgG and IgM) levels after IU100 treatment indicated its enhancing role in cellular and humoral immunity. In addition, oral administration of IU100 increased serum cytokine (IL-1β, IL-2, IL-4, IL-6, IFN-γ, TNF-α) levels dose-dependently, which are associated with CTX-induced shifts in the Th1/Th2 balance. The probiotic IU100 also modulated the composition of gut microbiota by reducing the Firmicutes/Bacteroidetes ratio; increasing beneficial Muribaculaceae and the Lachnospiraceae NK4A136 group; and inhibiting harmful Clostridium sensu stricto 1, Faecalibaculum and Staphylococcus at the genus level. The above genera were found to be correlated with serum cytokines and antibody levels. These findings suggest that IU100 effectively enhances the immune function of immunosuppressed mice, induced by CTX, by regulating gut microbiota.
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Affiliation(s)
- Limian Zhou
- Key Laboratory of Functional Dairy, Department of Nutrition and Health, China Agricultural University, Beijing 100190, China; (L.Z.)
- School of Food and Biological Engineering, Hefei University of Technology, Hefei 230601, China
| | - Xindi Yin
- Key Laboratory of Functional Dairy, Department of Nutrition and Health, China Agricultural University, Beijing 100190, China; (L.Z.)
| | - Bing Fang
- Key Laboratory of Functional Dairy, Department of Nutrition and Health, China Agricultural University, Beijing 100190, China; (L.Z.)
| | - Jingjing He
- Key Laboratory of Functional Dairy, Department of Nutrition and Health, China Agricultural University, Beijing 100190, China; (L.Z.)
| | - Jing Zhan
- Key Laboratory of Functional Dairy, Department of Nutrition and Health, China Agricultural University, Beijing 100190, China; (L.Z.)
| | - Xiaoxu Zhang
- Key Laboratory of Functional Dairy, Department of Nutrition and Health, China Agricultural University, Beijing 100190, China; (L.Z.)
| | - Ran Wang
- Key Laboratory of Functional Dairy, Department of Nutrition and Health, China Agricultural University, Beijing 100190, China; (L.Z.)
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Zhou L, Yin X, Fang B, He J, Zhan J, Zhang X, Wang R. Effects of Bifidobacterium animalis subsp. lactis IU100 on Immunomodulation and Gut Microbiota in Immunosuppressed Mice. Microorganisms 2024; 12:493. [PMID: 38543544 DOI: 10.3390/microorganisms12030493if:] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Revised: 02/24/2024] [Accepted: 02/28/2024] [Indexed: 07/26/2024] Open
Abstract
Probiotics are live microorganisms with immunomodulatory effects in a strain-specific and dose-dependent manner. Bifidobacterium animalis subsp. lactis IU100 is a new probiotic strain isolated from healthy adults. This study aimed to evaluate the effects of IU100 on cyclophosphamide (CTX)-induced immunosuppression in mice. The results showed that IU100 significantly ameliorated CTX-induced decreases in body weight and immune organ indices. The promoted delayed-type hypersensitivity, serum hemolysins and immunoglobulin (IgA, IgG and IgM) levels after IU100 treatment indicated its enhancing role in cellular and humoral immunity. In addition, oral administration of IU100 increased serum cytokine (IL-1β, IL-2, IL-4, IL-6, IFN-γ, TNF-α) levels dose-dependently, which are associated with CTX-induced shifts in the Th1/Th2 balance. The probiotic IU100 also modulated the composition of gut microbiota by reducing the Firmicutes/Bacteroidetes ratio; increasing beneficial Muribaculaceae and the Lachnospiraceae NK4A136 group; and inhibiting harmful Clostridium sensu stricto 1, Faecalibaculum and Staphylococcus at the genus level. The above genera were found to be correlated with serum cytokines and antibody levels. These findings suggest that IU100 effectively enhances the immune function of immunosuppressed mice, induced by CTX, by regulating gut microbiota.
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Affiliation(s)
- Limian Zhou
- Key Laboratory of Functional Dairy, Department of Nutrition and Health, China Agricultural University, Beijing 100190, China
- School of Food and Biological Engineering, Hefei University of Technology, Hefei 230601, China
| | - Xindi Yin
- Key Laboratory of Functional Dairy, Department of Nutrition and Health, China Agricultural University, Beijing 100190, China
| | - Bing Fang
- Key Laboratory of Functional Dairy, Department of Nutrition and Health, China Agricultural University, Beijing 100190, China
| | - Jingjing He
- Key Laboratory of Functional Dairy, Department of Nutrition and Health, China Agricultural University, Beijing 100190, China
| | - Jing Zhan
- Key Laboratory of Functional Dairy, Department of Nutrition and Health, China Agricultural University, Beijing 100190, China
| | - Xiaoxu Zhang
- Key Laboratory of Functional Dairy, Department of Nutrition and Health, China Agricultural University, Beijing 100190, China
| | - Ran Wang
- Key Laboratory of Functional Dairy, Department of Nutrition and Health, China Agricultural University, Beijing 100190, China
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Vélez C, Clauzure M, Williamson D, Koncurat MA, Barbeito C. IFN-γ and IL-10: seric and placental profile during pig gestation Seric and placental cytokines in pig gestation. AN ACAD BRAS CIENC 2023; 95:e20201160. [PMID: 37075349 DOI: 10.1590/0001-3765202320201160] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Accepted: 10/25/2020] [Indexed: 04/21/2023] Open
Abstract
Concentration of interferon-gamma and interleukin-10 in maternal serum and in maternal and fetal porcine placental extracts from different gestation periods was determined. Crossbred pigs' placental samples of 17, 30, 60, 70, and 114 days gestation and non-pregnant uteri were used. Interferon-gamma concentration was increased at the placental interface at 17 days, in maternal and fetal placenta, and decreased significantly in the remaining gestation periods. Interferon-gamma showed a peak in serum at 60 days. Regarding interleukin-10, placental tissue concentrations were unaltered, there were no significant differences with non-gestating uteri samples. In serum interleukin-10 increased at 17, 60, and 114 days gestation. At 17 days there are uterus structural and molecular changes that allow the embryos implantation and placenta development. The presence of interferon-gamma found at this moment in the interface would favor that placental growth. Moreover, its significant increase in serum at 60 days, would generate a proinflammatory cytokine pattern that facility the placental remodeling characteristic of this moment of porcine gestation. On the other hand, a significant interleukin-10 increase in serum at 17, 60 and 114 days could indicate its immunoregulatory role at a systemic level during pig gestation.
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Affiliation(s)
- Carolina Vélez
- Faculty of Veterinary Science, National University of La Pampa (UNLPam), Calle 5, 116, General Pico, 6360 La Pampa, Argentina
- National Scientific and Technical Research Council (CONICET), Godoy Cruz 2290, C1425FQB Buenos Aires, Argentina
| | - Mariángeles Clauzure
- Faculty of Veterinary Science, National University of La Pampa (UNLPam), Calle 5, 116, General Pico, 6360 La Pampa, Argentina
- National Scientific and Technical Research Council (CONICET), Godoy Cruz 2290, C1425FQB Buenos Aires, Argentina
| | - Delia Williamson
- Faculty of Veterinary Science, National University of La Pampa (UNLPam), Calle 5, 116, General Pico, 6360 La Pampa, Argentina
| | - Mirta A Koncurat
- Faculty of Veterinary Science, National University of La Pampa (UNLPam), Calle 5, 116, General Pico, 6360 La Pampa, Argentina
| | - Claudio Barbeito
- National Scientific and Technical Research Council (CONICET), Godoy Cruz 2290, C1425FQB Buenos Aires, Argentina
- Laboratory of Descriptive, Comparative and Experimental Histology and Embryology, School of Veterinary Science, National University of La Plata, Av. 60, 118, B1900 La Plata, Buenos Aires, Argentina
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Qu D, Feng S, Li M, Yu L, Tian F, Zhang H, Chen W, Zhai Q. Effects of Bifidobacteria bifidum strains on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced acute colitis and its potential mechanism. FOOD BIOSCI 2023. [DOI: 10.1016/j.fbio.2023.102387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
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Downregulation of miR-671-5p promotes IL-10 mRNA increase in porcine moDCs stimulated with the probiotic BB12. Mol Biol Rep 2023; 50:919-925. [PMID: 36334231 DOI: 10.1007/s11033-022-08040-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 10/18/2022] [Indexed: 11/08/2022]
Abstract
BACKGROUND Previous work showed that the microRNA (miRNA) miR-671-5p was upregulated in monocyte-derived dendritic cells (moDCs) stimulated with Bifidobacterium animalis subsp. lactis BB12 (BB12) with no increase in IL-10 after six hours of stimulation. In this work, we performed an in silico prediction of genes targeted by miR-671-5p and which are the terms and pathways involved with it. Also, miR-671-5p was transiently downregulated to assess its effect on IL-10 regulation. METHODS AND RESULTS First, we performed a Gene Ontology enrichment analysis to predict immune response terms and pathways involved with miR-671-5p. Some of the terms and pathways found were related to the immune response promoted by the probiotic, as the terms "negative regulation of the inflammatory response to an antigenic stimulus" and "cancer" were highlighted. Then, to assess the role of miR-671-5p in IL-10 regulation, moDCs were derived from porcine peripheral blood and later transfected with miR-671-5p antisense oligonucleotide (ASO). Flow cytometry was employed to evaluate the transfection efficiency. Then, the moDCs were stimulated with BB12, and the expression of IL-10 was assessed by RT-qPCR and ELISA. An increase in IL-10 transcript in miR-671-5p-ASO-transfected moDCs stimulated with BB12 was observed compared with moDCs stimulated with BB12 but not transfected. These results suggest the participation of miR-671-5p as a negative regulator of IL-10. CONCLUSION These findings suggest that miR-671-5p participates in the downregulation of IL-10, as previously predicted in silico by our work group. miR-671-5p could play an essential role in the immunomodulation promoted by the probiotic BB12.
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Bifidobacterium animalis Promotes the Growth of Weaning Piglets by Improving Intestinal Development, Enhancing Antioxidant Capacity, and Modulating Gut Microbiota. Appl Environ Microbiol 2022; 88:e0129622. [DOI: 10.1128/aem.01296-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
In the modern swine industry, weaning is a critical period in the pig’s life cycle. Sudden dietary, social, and environmental changes can easily lead to gut microbiota dysbiosis, diarrhea, and a decrease in growth performance.
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Kaur H, Ali SA. Probiotics and gut microbiota: mechanistic insights into gut immune homeostasis through TLR pathway regulation. Food Funct 2022; 13:7423-7447. [DOI: 10.1039/d2fo00911k] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Consumption of probiotics as a useful functional food improves the host's wellbeing, and, when paired with prebiotics (indigestible dietary fibre/carbohydrate), often benefits the host through anaerobic fermentation.
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Affiliation(s)
- Harpreet Kaur
- Animal Biochemistry Division, ICAR-NDRI, 132001, India
| | - Syed Azmal Ali
- Cell Biology and Proteomics Lab, Animal Biotechnology Center, ICAR-NDRI, 132001, India
- Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
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Arenas-Padilla M, González-Rascón A, Hernández-Mendoza A, Calderón de la Barca AM, Hernández J, Mata-Haro V. Immunomodulation by Bifidobacterium animalis subsp. lactis Bb12: Integrative Analysis of miRNA Expression and TLR2 Pathway-Related Target Proteins in Swine Monocytes. Probiotics Antimicrob Proteins 2021; 14:510-522. [PMID: 34283392 PMCID: PMC8289881 DOI: 10.1007/s12602-021-09816-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/25/2021] [Indexed: 12/12/2022]
Abstract
Bifidobacterium animalis subsp. lactis Bb12 is a widely used probiotic that provides numerous health benefits to its host, many due to its immunomodulatory properties. Although the precise mechanism of modulation is still under investigation, several reports associate the interaction of TLR2 with components of the bacterial cell wall inducing a signaling cascade that culminates with the production of cytokines and co-stimulatory molecules. MicroRNAs (miRNAs) have emerged as important post-transcriptional regulators of immune responses, including those toward probiotics. In this study, we analyzed the miRNA expression profile in swine monocytes exposed to Bb12 by using an anti-TLR2 blocking strategy and Bb12 involvement in the regulation of the TLR2 pathway. As a result, the expression of 40 miRNAs was influenced by the treatments (p < 0.01), and 15 differentially expressed miRNAs with validated miRNA–mRNA interactions with around 26 proteins related to the TLR2 pathway were identified. The miRNAs upregulated in response to Bb12 included miR-15a-5p, miR-16-5p, miR-26a-5p, miR-29b-3p, and miR-30d-5p, and the following showed downregulation: miR-181a-5p, miR-19b-3p, miR-21-5p, miR-23a-5p, and miR-221-3p. The expression of let-7c-5p, let-7f-5p, miR-146b-5p, miR-150-5p, and miR-155-5p was increased by Bb12 only when TLR2 was blocked. The identified miRNA common targets were downstream proteins from bacterial recognition via TLR2, such as MyD88, TRAF6, and MAPK members; transcription factors such as NF-κB and AP-1; and cytokines such as IL-6, IL-10, and TNF-α. TLR2 participation was abrogated by anti-TLR2 antibody and suggests that bacterial recognition is complemented by other receptors since there were still changes in the microtranscriptome.
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Affiliation(s)
- Marina Arenas-Padilla
- Laboratorio de Microbiología e Inmunología, Centro de Investigación en Alimentación y Desarrollo, A.C. (CIAD), Carretera Gustavo E. Astiazarán 46, 83304, Hermosillo, Sonora, Mexico
| | - Anna González-Rascón
- Laboratorio de Microbiología e Inmunología, Centro de Investigación en Alimentación y Desarrollo, A.C. (CIAD), Carretera Gustavo E. Astiazarán 46, 83304, Hermosillo, Sonora, Mexico
| | - Adrián Hernández-Mendoza
- Laboratorio de Química y Biotecnología de Productos Lácteos, Centro de Investigación en Alimentación y Desarrollo A.C. (CIAD), Carretera Gustavo E. Astiazarán 46, 83304, Hermosillo, Sonora, Mexico
| | - Ana María Calderón de la Barca
- Departamento de Nutrición y Metabolismo, Centro de Investigación en Alimentación y Desarrollo A.C. (CIAD), Carretera Gustavo E. Astiazarán 46, 83304, Hermosillo, Sonora, Mexico
| | - Jesús Hernández
- Laboratorio de Inmunología, Centro de Investigación en Alimentación y Desarrollo A.C. (CIAD), Carretera Gustavo E. Astiazarán 46, 83304, Hermosillo, Sonora, Mexico
| | - Verónica Mata-Haro
- Laboratorio de Microbiología e Inmunología, Centro de Investigación en Alimentación y Desarrollo, A.C. (CIAD), Carretera Gustavo E. Astiazarán 46, 83304, Hermosillo, Sonora, Mexico.
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Okolo CC, Nweze NE, Eze IJ. Hematobiochemical and Immunological Responses of Rats Treated with Multi-strain Probiotics and Infected with Trypanosoma brucei. Probiotics Antimicrob Proteins 2021; 12:952-960. [PMID: 31617160 DOI: 10.1007/s12602-019-09592-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
The effects of treatment with probiotics on the immunological and hematobiochemical changes in Trypanosoma brucei infection were investigated. Probiotic strains used are Bifidobacterium BB-12, Lactobacillus acidophilus LA-5, Lactobacillus delbrueckii LBY-27, Lactobacillus paracasei LC-01, and Streptococcus thermophilus STY-31. Thirty rats randomly assigned to five groups were used in the experiment. Groups A to C received 1 × 109 CFU, 5 × 109 CFU, and 10 × 109 CFU of the multi-strain probiotics daily and respectively from day 0 post-supplementation (PS) to termination. Group D and E were the infected and uninfected controls respectively. On day seven PS, groups A to D were challenged intraperitoneally with approximately 1 × 106 trypanosomes. Parasitemia, nitric oxide level, hematobiochemical parameters, and antibody titer to heterologous antigen stimulation were monitored post-infection. By days 7 and 16 PS, probiotics-treated groups had significantly lower (p < 0.05) mean creatinine concentration than the controls; however, on day 7 PS, there were no significant variations in the leukocyte counts (LC), total erythrocyte counts (TEC), and the packed cell volume (PCV) in all experimental groups. Following infection, by day 16 PS, the pre-patent period, parasitemia levels, and antibody titer were similar in all infected groups. Furthermore, the probiotics-treated groups and the infected control had significantly lower PCV, TEC, and LC values when compared to the uninfected control, and probiotics treated groups (A and C) had only marginally lower nitric oxide levels than the infected control. Treatment with the probiotic strains gave a creatinine-lowering effect, was innocuous to the hematopoietic system, but was not sufficiently immunostimulatory in trypanosomosis.
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Affiliation(s)
| | | | - Ifeanyi James Eze
- Department of Veterinary Medicine, University of Nigeria, Nsukka, Enugu, 410001, Nigeria
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The Probiotic BB12 Induces MicroRNAs Involved in Antigen Processing and Presentation in Porcine Monocyte-Derived Dendritic Cells. Int J Mol Sci 2020; 21:ijms21030687. [PMID: 31972983 PMCID: PMC7037397 DOI: 10.3390/ijms21030687] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Revised: 01/07/2020] [Accepted: 01/07/2020] [Indexed: 01/22/2023] Open
Abstract
MicroRNAs (miRNAs) mediate the regulation of gene expression. Several reports indicate that probiotics induce miRNA-mediated immunomodulation at different levels, such as cytokine production and the up-regulation of several markers related to antigen presentation in antigen-presenting cells. The objective of this work was to identify target genes of miRNAs that are involved in the processing and presentation of antigens in monocyte-derived dendritic cells (moDCs) stimulated with the probiotic Bifidobacterium animalis ssp. lactis BB12 (BB12). First, an in silico prediction analysis for a putative miRNA binding site within a given mRNA target was performed using RNAHybrid software with mature sequences of differentially expressed miRNAs retrieved from a Genbank data set that included BB12-stimulated and unstimulated porcine monocytes. From them, 23 genes resulted in targets of 19 miRNAs, highlighting miR-30b-3p, miR-671-5p, and miR-9858-5p, whose targets were costimulatory molecules, and were overexpressed (p < 0.05) in BB12-stimulated moDCs. The analysis of moDCs showed that the percentage of cells expressing SLA-DR+CD80+ decreased significantly (p = 0.0081) in BB12-stimulated moDCs; interleukin (IL)-10 production was unchanged at 6 h but increased after 24 h of culture in the presence of BB12 (p < 0.001). In summary, our results suggest that SLA-DR and CD80 can be down-regulated by miRNAs miR-30b-3p, miR-671-5p, and miR-9858-5p, while miR-671-5p targets IL-10.
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Bifidobacterium lactis BB-12 Attenuates Macrophage Aging Induced by D-Galactose and Promotes M2 Macrophage Polarization. J Immunol Res 2019; 2019:4657928. [PMID: 31930149 PMCID: PMC6942849 DOI: 10.1155/2019/4657928] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Revised: 10/10/2019] [Accepted: 11/14/2019] [Indexed: 02/06/2023] Open
Abstract
Immunosenescence comprises a set of dynamic changes occurring in innate and adaptive immune systems, and macrophage aging plays an important role in innate and adaptive immunosenescence. However, function and polarization changes in aging macrophages have not been fully evaluated, and no effective method for delaying macrophage senescence is currently available. The results of this study reveal that D-galactose (D-gal) can promote J774A.1 macrophage senescence and induce macrophage M1 polarization differentiation. Bifidobacterium lactis BB-12 can significantly inhibit J774A.1 macrophage senescence induced by D-gal. IL-6 and IL-12 levels in the BB-12 groups remarkably decreased compared with that in the D-gal group, and the M2 marker, IL-10, and Arg-1 mRNA levels increased in the BB-12 group. BB-12 inhibited the expression of p-signal transducer and activator of transcription 1 (STAT1) and promoted p-STAT6 expression. In summary, the present study indicates that BB-12 can attenuate the J774A.1 macrophage senescence and induce M2 macrophage polarization, thereby indicating the potential of BB-12 to slow down immunosenescence and inflamm-aging.
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Li F, Wang M, Wang J, Li R, Zhang Y. Alterations to the Gut Microbiota and Their Correlation With Inflammatory Factors in Chronic Kidney Disease. Front Cell Infect Microbiol 2019; 9:206. [PMID: 31245306 PMCID: PMC6581668 DOI: 10.3389/fcimb.2019.00206] [Citation(s) in RCA: 192] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2019] [Accepted: 05/27/2019] [Indexed: 12/17/2022] Open
Abstract
Alterations to the gut microbiota have been previously suggested to be tightly linked to chronic systemic inflammation, which is a major contributing factor to complications and disease progression in chronic kidney disease (CKD). Nevertheless, the effect of gut dysbiosis on the pathogenesis and/or production of inflammatory factors in CKD has not been extensively studied to date. In the present study, we conducted 16S ribosomal DNA pyrosequencing using fecal microbiota samples and analyzed the production of serum inflammatory factors in 50 patients with CKD and 22 healthy control (HC) subjects. The results revealed that compared to the HC subjects, patients with CKD exhibited a significant reduction in the richness and structure of their fecal microbiota. At the phylum level, compared to the HC group, patients with CKD also presented reduced abundance of Actinobacteria but increased abundance of Verrucomicrobia. Moreover, the genera Lactobacillus, Clostridium IV, Paraprevotella, Clostridium sensu stricto, Desulfovibrio, and Alloprevotella were enriched in the fecal samples of patients with CKD, while Akkermansia and Parasutterella were enriched in those of the HC subjects. The abundance of Akkermansia in the CKD group was significantly lower than that in the HC group (3.08 vs. 0.67%); this decrease in the abundance of Akkermansia, an important probiotic, in patients with CKD is a striking discovery as it has not been previously reported. Finally, we analyzed whether these changes to the fecal microbiota correlated with CKD clinical characteristics and/or the production of known inflammatory factors. Altered levels of the microbiota genera Parasutterella, Lactobacillus, Paraprevotella, Clostridium sensu stricto, and Desulfovibrio were shown to be correlated with CKD disease-severity indicators, including the estimated glomerular filtration rate. Most notably, Akkermansia was significantly negatively correlated with the production of interleukin-10. The results of the present study suggest that microbiota dysbiosis may promote chronic systemic inflammation in CKD. Furthermore, they support that modifying the gut microbiota, especially Akkermansia, may be a promising potential therapeutic strategy to attenuate the progression of, and/or systemic inflammation in, CKD.
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Affiliation(s)
- FengXia Li
- Department of Gastroenterology, Shanxi Provincial People's Hospital, Taiyuan, China
| | - MeiHong Wang
- People's Hospital Affiliated to Shanxi Medical University, Taiyuan, China
| | - JunPing Wang
- Department of Gastroenterology, Shanxi Provincial People's Hospital, Taiyuan, China
| | - RongShan Li
- Department of Nephrology, Shanxi Provincial People's Hospital, Taiyuan, China
| | - YaQiong Zhang
- People's Hospital Affiliated to Shanxi Medical University, Taiyuan, China
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