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Silva-Veiga FM, Marinho TS, de Souza-Mello V, Aguila MB, Mandarim-de-Lacerda CA. Tirzepatide, a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), positively impacts the altered microbiota of obese, diabetic, ovariectomized mice. Life Sci 2025; 361:123310. [PMID: 39675551 DOI: 10.1016/j.lfs.2024.123310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2024] [Revised: 11/26/2024] [Accepted: 12/11/2024] [Indexed: 12/17/2024]
Abstract
The study aimed to verify the effect of Tirzepatide (Tzp, a dual agonist GIP/GLP-1) on intestinal health and microbiota balance in an obese diabetic ovariectomized (Ovx) mice model. Female C57BL/6 mice with Ovx and diet-induced obesity with diabetes were treated with Tzp (10 nmol/kg) for four weeks. Control (C) and obese-diabetic subgroups (Od) were formed (group abbreviations: O, Ovx; T, Tzp; n = 30/group): C, CT, CO, COT, Od, OdT, OdO, OdOT. The ileum was structurally and molecularly studied, and cecal feces had microbial DNA determined. Tzp improved the intestinal barrier structure and protection. Cldn12 (Claudin 12) increased, and Muc2 (Mucin 2) decreased. JamA (junctional adhesion molecules) and Ocln (Occludin) increased. Tzp mitigated macrophage activation and inflammation, altered composition, and the contribution to microbiota: Firmicutes decreased, and Bacteroidetes increased, changing the Firmicutes / Bacteroidetes ratio. Proteobacteria, Actinobacteria, Bifidobacterium, and Clostridium increased. In addition, Bacteroides, Prevotella, and Akkermansia increased. PCA indicated a significant action of Cd14, Muc2, and Tlr4 on CO and Il17 on OdO; Il10, Cd206, Cd12, Ocln, and JamA in Od. Bacteroides, Bifidobacterium, Clostridium, Actinobacteria, and Bacteroides were enhanced in CT and COT, Provotella, Proteobacteria, and Firmicutes in CO, Od, OdT, OdO, and Akkermansia in OdOT. In conclusion, the intestinal barrier function in our model is compromised by alterations in phylogenetic diversity and intestinal microbiota, which characterize dysbiosis and potentially enable the influx of toxins into other tissues. Treatment with Tzp demonstrated the ability to reverse intestinal dysbiosis, help repair intestinal barrier integrity, and mitigate possible endotoxemia through anti-inflammatory signaling pathways.
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Affiliation(s)
- Flavia Maria Silva-Veiga
- Laboratory of Morphometry, Metabolism, and Cardiovascular Disease, Institute of Biology, Biomedical Center, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Thatiany Souza Marinho
- Laboratory of Morphometry, Metabolism, and Cardiovascular Disease, Institute of Biology, Biomedical Center, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Vanessa de Souza-Mello
- Laboratory of Morphometry, Metabolism, and Cardiovascular Disease, Institute of Biology, Biomedical Center, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Marcia Barbosa Aguila
- Laboratory of Morphometry, Metabolism, and Cardiovascular Disease, Institute of Biology, Biomedical Center, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.
| | - Carlos Alberto Mandarim-de-Lacerda
- Laboratory of Morphometry, Metabolism, and Cardiovascular Disease, Institute of Biology, Biomedical Center, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.
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Yang R, Wang H, Chen D, Cai Q, Zhu J, Yuan S, Wang F, Xu X. The effect of in-hospital breast milk intake on the gut microbiota of preterm infants. Clin Nutr ESPEN 2024; 60:146-155. [PMID: 38479903 DOI: 10.1016/j.clnesp.2024.01.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Revised: 01/11/2024] [Accepted: 01/22/2024] [Indexed: 04/13/2024]
Abstract
OBJECTIVE The aim of this study was to explore the effect of in-hospital breast milk intake on the development of early gut microbiota in preterm infants in two dimensions: longitudinal over time and cross-sectional between groups. METHODS Researchers collected preterm infants' general data baseline characteristics, recorded their daily breast milk intake, probiotics, and antibiotics use, and collected their stool specimens at 1st week, 2 nd week, 3rd week and 4th week after birth. The researchers analyzed the effect of breast milk on gut microbiota of preterm infants by bioinformatics methods of intra-group longitudinal variation of gut microbiota structure and diversity in preterm infants and cross-sectional differences between >70 % in-hospital breast milk intake (BM) group and ≤70 % (PF) group. RESULTS A total of 60 preterm infants were included in this study, and a total of 213 stool specimens were retained. BM had statistically different Shannon and Simpson indices between the first and fourth week after admission (P < 0.05), both of them showed a lower diversity in the later week than in the previous week. The Shannon index and Simpson index of BM from week 3 onwards were statistically different from PF (P < 0.05), and the Shannon index and Simpson index of BM were lower than those of PF. Significantly statistical differences (P < 0.05) were found in the beta diversity of gut microbiota in preterm infants as time progressed, and both showed a lower beta diversity in the later week than in the preceding week. The dominant taxa of PF in the first postnatal week were Bifidobacterium animalis, etc., the dominant taxa of BM in the third postnatal week were Clostridium_sensu_stricto _1, etc. CONCLUSIONS: The development and evolution of gut microbiota in preterm infants' in-hospital period was a continuous, non-random process, and similar trends in species composition and changes in gut microbes emerged in preterm infants with different ratio of breast milk intake. In the NICU setting, alpha diversity was lower in preterm infants in the >70 % breast milk intake group than in the ≤70 % group when compared between groups at the same time, which may be related to delayed maturation of gut microbes and represents a more developmental gut time window.
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Affiliation(s)
- Rui Yang
- School of Nursing, Capital Medical University, Beijing, China
| | - Hua Wang
- Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Danqi Chen
- Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Qian Cai
- Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Jiajun Zhu
- Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Shuiqin Yuan
- Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Fang Wang
- Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
| | - Xinfen Xu
- Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
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Tamés H, Sabater C, Royo F, Margolles A, Falcón JM, Ruas-Madiedo P, Ruiz L. Mouse intestinal microbiome modulation by oral administration of a GABA-producing Bifidobacterium adolescentis strain. Microbiol Spectr 2024; 12:e0258023. [PMID: 37991375 PMCID: PMC10783132 DOI: 10.1128/spectrum.02580-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Accepted: 10/15/2023] [Indexed: 11/23/2023] Open
Abstract
IMPORTANCE The gut microbiome-brain communication signaling has emerged in recent years as a novel target for intervention with the potential to ameliorate some conditions associated with the central nervous system. Hence, probiotics with capacity to produce neurotransmitters, for instance, have come up as appealing alternatives to treat disorders associated with disbalanced neurotransmitters. Herein, we further deep into the effects of administering a gamma-aminobutyric acid (GABA)-producing Bifidobacterium strain, previously demonstrated to contribute to reduce serum glutamate levels, in the gut microbiome composition and metabolic activity in a mouse model. Our results demonstrate that the GABA-producing strain administration results in a specific pattern of gut microbiota modulation, different from the one observed in animals receiving non-GABA-producing strains. This opens new avenues to delineate the specific mechanisms by which IPLA60004 administration contributes to reducing serum glutamate levels and to ascertain whether this effect could exert health benefits in patients of diseases associated with high-glutamate serum concentrations.
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Affiliation(s)
- Héctor Tamés
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias-Consejo Superior de Investigaciones Científicas (IPLA-CSIC), Paseo Río Linares s/n, Villaviciosa, Asturias, Spain
- Functionality and Ecology of Beneficial Microbes (MicroHealth) Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Asturias, Spain
| | - Carlos Sabater
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias-Consejo Superior de Investigaciones Científicas (IPLA-CSIC), Paseo Río Linares s/n, Villaviciosa, Asturias, Spain
- Functionality and Ecology of Beneficial Microbes (MicroHealth) Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Asturias, Spain
| | - Félix Royo
- Exosomes Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas Y Digestivas (CIBERehd), Madrid, Spain
- IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
| | - Abelardo Margolles
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias-Consejo Superior de Investigaciones Científicas (IPLA-CSIC), Paseo Río Linares s/n, Villaviciosa, Asturias, Spain
- Functionality and Ecology of Beneficial Microbes (MicroHealth) Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Asturias, Spain
| | - Juan Manuel Falcón
- Exosomes Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas Y Digestivas (CIBERehd), Madrid, Spain
- IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
| | - Patricia Ruas-Madiedo
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias-Consejo Superior de Investigaciones Científicas (IPLA-CSIC), Paseo Río Linares s/n, Villaviciosa, Asturias, Spain
- Functionality and Ecology of Beneficial Microbes (MicroHealth) Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Asturias, Spain
| | - Lorena Ruiz
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias-Consejo Superior de Investigaciones Científicas (IPLA-CSIC), Paseo Río Linares s/n, Villaviciosa, Asturias, Spain
- Functionality and Ecology of Beneficial Microbes (MicroHealth) Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Asturias, Spain
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Bishu S. Nurturing the Gut, Moms with IBD and Their Babies. J Crohns Colitis 2023; 17:1705-1706. [PMID: 37749070 PMCID: PMC10673811 DOI: 10.1093/ecco-jcc/jjad139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/27/2023]
Affiliation(s)
- Shrinivas Bishu
- Crohn’s and Colitis Center, University of Michigan, Ann Arbor, MI, USA
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SHIMADA M, KAWASE Y, SONOYAMA K, OGURA Y, HAYASHI T, YOKOTA A, FUKIYA S. Development of an improved colonization system for human-derived Bifidobacterium longum subsp. longum in conventional mice through the feeding of raffinose or 1-kestose. BIOSCIENCE OF MICROBIOTA, FOOD AND HEALTH 2023; 43:110-119. [PMID: 38562544 PMCID: PMC10981944 DOI: 10.12938/bmfh.2023-055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Accepted: 11/05/2023] [Indexed: 04/04/2024]
Abstract
How bifidobacteria colonize and survive in the intestine is not fully understood. The administration of bifidobacteria to conventional mice can be used to evaluate their ability to colonize the intestine in the presence of endogenous gut microbiota. However, human-derived bifidobacteria do not readily colonize the intestines of conventional mice, and although colonization by Bifidobacterium breve UCC2003 has been achieved, the viability of such populations requires improvement. Therefore, we aimed to establish a colonization system with human-derived bifidobacteria of high viability in conventional mice using Bifidobacterium longum subsp. longum 105-A. Lactose, raffinose, and 1-kestose were identified as the preferred carbohydrate sources for the growth of this strain in culture. The administration of B. longum 105-A to conventional BALB/c mice fed these carbohydrates showed that diets containing 6% (w/w) raffinose or 1-kestose facilitated colonization with >108 colony-forming units/g feces for 2 weeks. The population of this strain was more stable in the raffinose-fed group than in the 1-kestose-fed group. The ingestion of these prebiotics had a greater impact on the composition of the microbiota than the administration of B. longum 105-A. The ingestion of these prebiotics also increased the fecal concentrations of organic acids, which was indicative of greater intestinal fermentation. Collectively, we established a colonization system for B. longum 105-A with high viability in conventional mice by feeding the mice raffinose or 1-kestose. This system should be useful for elucidation of the mechanisms of colonization and survival of bifidobacteria in the intestines in the presence of the endogenous gut microbiota.
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Affiliation(s)
- Mina SHIMADA
- Laboratory of Microbial Physiology, Research Faculty of
Agriculture, Hokkaido University, Kita 9, Nishi 9, Kita-ku, Sapporo, Hokkaido 060-8589,
Japan
| | - Youhei KAWASE
- Laboratory of Microbial Physiology, Research Faculty of
Agriculture, Hokkaido University, Kita 9, Nishi 9, Kita-ku, Sapporo, Hokkaido 060-8589,
Japan
| | - Kei SONOYAMA
- Laboratory of Food Biochemistry, Research Faculty of
Agriculture, Hokkaido University, Kita 9, Nishi 9, Kita-ku, Sapporo, Hokkaido 060-8589,
Japan
| | - Yoshitoshi OGURA
- Department of Bacteriology, Faculty of Medical Sciences,
Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka-shi, Fukuoka 812-8582, Japan
- Department of Infectious Medicine, Kurume University School
of Medicine, 67 Asahi-machi, Kurume-shi, Fukuoka 830-0011, Japan
| | - Tetsuya HAYASHI
- Department of Bacteriology, Faculty of Medical Sciences,
Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka-shi, Fukuoka 812-8582, Japan
| | - Atsushi YOKOTA
- Laboratory of Microbial Physiology, Research Faculty of
Agriculture, Hokkaido University, Kita 9, Nishi 9, Kita-ku, Sapporo, Hokkaido 060-8589,
Japan
| | - Satoru FUKIYA
- Laboratory of Microbial Physiology, Research Faculty of
Agriculture, Hokkaido University, Kita 9, Nishi 9, Kita-ku, Sapporo, Hokkaido 060-8589,
Japan
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de Oliveira Vieira KC, da Silva ABB, Felício SA, Lira FS, de Figueiredo C, Bezirtzoglou E, Pereira VC, Nakagaki WR, Nai GA, Winkelströter LK. Orange juice containing Pediococcus acidilactici CE51 modulates the intestinal microbiota and reduces induced inflammation in a murine model of colitis. Sci Rep 2023; 13:18513. [PMID: 37898635 PMCID: PMC10613252 DOI: 10.1038/s41598-023-45819-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Accepted: 10/24/2023] [Indexed: 10/30/2023] Open
Abstract
The management of inflammatory bowel diseases has been widely investigated, especially ulcerative colitis. Thus, studies with the application of new probiotic products are needed in the prevention/treatment of these clinical conditions. The objective of this work was to evaluate the effects of probiotic orange juice containing Pediococcus acidilactici CE51 in a murine model of colitis. 45 male Swiss lineage mice were used, divided into five groups (n = 9): control, colitis, colitis + probiotic (probiotic orange juice containing CE51), colitis + placebo (orange juice) and colitis + sulfasalazine (10 mg/kg/Weight). The induction of colitis was performed with dextran sodium sulfate (3%). The treatment time was 5 and 15 days after induction. Histopathological analysis, serum measurements of TNF-α and C-reactive protein and metagenomic analysis of feces were performed after euthanasia. Probiotic treatment reduced inflammation in the small intestine, large intestine and spleen. The probiotic did not alter the serum dosages of TNF-α and C-reactive protein. Their use maintained the quantitative ratio of the phylum Firmicutes/Bacteroidetes and increased Lactobacillus helveticus with 15 days of treatment (p < 0.05). The probiotic orange juice containing P. acidilactici CE51 positively modulated the gut microbiota composition and attenuated the inflammation induced in colitis.
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Affiliation(s)
- Karolinny Cristiny de Oliveira Vieira
- Health Sciences Faculty, UNOESTE (University of Western Sao Paulo), 700, Jose Bongiovani St., Cidade Universitária, Presidente Prudente, Sao Paulo, 19050-920, Brazil
| | - Ana Beatriz Batista da Silva
- Master in Health Science, UNOESTE (University of Western Sao Paulo), 700, Jose Bongiovani St., Presidente Prudente, Sao Paulo, 19050-920, Brazil
| | - Suelen Aparecida Felício
- Master in Health Science, UNOESTE (University of Western Sao Paulo), 700, Jose Bongiovani St., Presidente Prudente, Sao Paulo, 19050-920, Brazil
| | - Fábio Santos Lira
- Department of Physical Education, Faculdade de Ciências e Tecnologia, Universidade Estadual Paulista, UNESP, Rua Roberto Simonsen, 305, Presidente Prudente, Sao Paulo, 19060-900, Brazil
| | - Caíque de Figueiredo
- Department of Physical Education, Faculdade de Ciências e Tecnologia, Universidade Estadual Paulista, UNESP, Rua Roberto Simonsen, 305, Presidente Prudente, Sao Paulo, 19060-900, Brazil
| | - Eugenia Bezirtzoglou
- Laboratory of Hygiene and Environmental Protection, Department of Medicine, Democritus University of Thrace, Dragana, 68100, Alexandroupolis, Greece
| | - Valéria Cataneli Pereira
- Health Sciences Faculty, UNOESTE (University of Western Sao Paulo), 700, Jose Bongiovani St., Cidade Universitária, Presidente Prudente, Sao Paulo, 19050-920, Brazil
- Master in Health Science, UNOESTE (University of Western Sao Paulo), 700, Jose Bongiovani St., Presidente Prudente, Sao Paulo, 19050-920, Brazil
| | - Wilson Romero Nakagaki
- Health Sciences Faculty, UNOESTE (University of Western Sao Paulo), 700, Jose Bongiovani St., Cidade Universitária, Presidente Prudente, Sao Paulo, 19050-920, Brazil
- Master in Health Science, UNOESTE (University of Western Sao Paulo), 700, Jose Bongiovani St., Presidente Prudente, Sao Paulo, 19050-920, Brazil
| | - Gisele Alborghetti Nai
- Health Sciences Faculty, UNOESTE (University of Western Sao Paulo), 700, Jose Bongiovani St., Cidade Universitária, Presidente Prudente, Sao Paulo, 19050-920, Brazil
| | - Lizziane Kretli Winkelströter
- Health Sciences Faculty, UNOESTE (University of Western Sao Paulo), 700, Jose Bongiovani St., Cidade Universitária, Presidente Prudente, Sao Paulo, 19050-920, Brazil.
- Master in Health Science, UNOESTE (University of Western Sao Paulo), 700, Jose Bongiovani St., Presidente Prudente, Sao Paulo, 19050-920, Brazil.
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Clostridium butyricum Prevents Dysbiosis and the Rise in Blood Pressure in Spontaneously Hypertensive Rats. Int J Mol Sci 2023; 24:ijms24054955. [PMID: 36902386 PMCID: PMC10002514 DOI: 10.3390/ijms24054955] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 02/13/2023] [Accepted: 02/15/2023] [Indexed: 03/08/2023] Open
Abstract
Hypertension is accompanied by dysbiosis and a decrease in the relative abundance of short-chain fatty acid (SCFA)-producing bacteria. However, there is no report to examine the role of C. butyricum in blood pressure regulation. We hypothesized that a decrease in the relative abundance of SCFA-producing bacteria in the gut was the cause of spontaneously hypertensive rats (SHR)-induced hypertension. C. butyricum and captopril were used to treat adult SHR for six weeks. C. butyricum modulated SHR-induced dysbiosis and significantly reduced systolic blood pressure (SBP) in SHR (p < 0.01). A 16S rRNA analysis determined changes in the relative abundance of the mainly SCFA-producing bacteria Akkermansia muciniphila, Lactobacillus amylovorus, and Agthobacter rectalis, which increased significantly. Total SCFAs, and particularly butyrate concentrations, in the SHR cecum and plasma were reduced (p < 0.05), while C. butyricum prevented this effect. Likewise, we supplemented SHR with butyrate for six weeks. We analyzed the flora composition, cecum SCFA concentration, and inflammatory response. The results showed that butyrate prevented SHR-induced hypertension and inflammation, and the decline of cecum SCFA concentrations (p < 0.05). This research revealed that increasing cecum butyrate concentrations by probiotics, or direct butyrate supplementation, prevented the adverse effects of SHR on intestinal flora, vascular, and blood pressure.
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Antioxidant activity and viability of Lacticaseibacillus rhamnosus, Lacticaseibacillus casei, and Co-culture in fermented tomato juice during refrigerated storage. FOOD BIOSCI 2022. [DOI: 10.1016/j.fbio.2022.102085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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Proctor A, Parvinroo S, Richie T, Jia X, Lee STM, Karp PD, Paley S, Kostic AD, Pierre JF, Wannemuehler MJ, Phillips GJ. Resources to Facilitate Use of the Altered Schaedler Flora (ASF) Mouse Model to Study Microbiome Function. mSystems 2022; 7:e0029322. [PMID: 35968975 PMCID: PMC9600240 DOI: 10.1128/msystems.00293-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Accepted: 07/20/2022] [Indexed: 12/24/2022] Open
Abstract
Animals colonized with a defined microbiota represent useful experimental systems to investigate microbiome function. The altered Schaedler flora (ASF) represents a consortium of eight murine bacterial species that have been used for more than 4 decades where the study of mice with a reduced microbiota is desired. In contrast to germ-free mice, or mice colonized with only one or two species, ASF mice show the normal gut structure and immune system development. To further expand the utility of the ASF, we have developed technical and bioinformatic resources to enable a systems-based analysis of microbiome function using this model. Here, we highlighted four distinct applications of these resources that enable and improve (i) measurements of the abundance of each ASF member by quantitative PCR; (ii) exploration and comparative analysis of ASF genomes and the metabolic pathways they encode that comprise the entire gut microbiome; (iii) global transcriptional profiling to identify genes whose expression responds to environmental changes within the gut; and (iv) discovery of genetic changes resulting from the evolutionary adaptation of the microbiota. These resources were designed to be accessible to a broad community of researchers that, in combination with conventionally-reared mice (i.e., with complex microbiome), should contribute to our understanding of microbiome structure and function. IMPORTANCE Improved experimental systems are needed to advance our understanding of how the gut microbiome influences processes of the mammalian host as well as microbial community structure and function. An approach that is receiving considerable attention is the use of animal models that harbor a stable microbiota of known composition, i.e., defined microbiota, which enables control over an otherwise highly complex and variable feature of mammalian biology. The altered Schaedler flora (ASF) consortium is a well-established defined microbiota model, where mice are stably colonized with 8 distinct murine bacterial species. To take better advantage of the ASF, we established new experimental and bioinformatics resources for researchers to make better use of this model as an experimental system to study microbiome function.
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Affiliation(s)
- Alexandra Proctor
- Department of Veterinary Microbiology, Iowa State University, Ames, Iowa, USA
| | - Shadi Parvinroo
- Department of Veterinary Microbiology, Iowa State University, Ames, Iowa, USA
| | - Tanner Richie
- Division of Biology, Kansas State University, Manhattan Kansas, USA
| | - Xinglin Jia
- Department of Veterinary Microbiology, Iowa State University, Ames, Iowa, USA
| | - Sonny T. M. Lee
- Division of Biology, Kansas State University, Manhattan Kansas, USA
| | - Peter D. Karp
- Bioinformatics Research Group, SRI International, Menlo Park, California, USA
| | - Suzanne Paley
- Bioinformatics Research Group, SRI International, Menlo Park, California, USA
| | - Aleksandar D. Kostic
- Department of Microbiology and Immunology, Joslin Diabetes Center, Harvard University, Cambridge Massachusetts, USA
| | - Joseph F. Pierre
- Department of Nutritional Sciences, University of Wisconsin-Madison, Madison Wisconsin, USA
| | | | - Gregory J. Phillips
- Department of Veterinary Microbiology, Iowa State University, Ames, Iowa, USA
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Ramalho JB, Spiazzi CC, Bicca DF, Rodrigues JF, Sehn CP, da Silva WP, Cibin FWS. Beneficial effects of Lactococcus lactis subsp. cremoris LL95 treatment in an LPS-induced depression-like model in mice. Behav Brain Res 2022; 426:113847. [PMID: 35306095 DOI: 10.1016/j.bbr.2022.113847] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Revised: 03/05/2022] [Accepted: 03/14/2022] [Indexed: 12/12/2022]
Abstract
Clinical evidence suggests that neuroinflammation, activation of the immune system, and the composition of the intestinal microbiota are involved in the pathology of depression. This study evaluated the effectiveness of a probiotic intervention using Lactococcus lactis subsp. cremoris LL95 in ameliorating mood disorders in a lipopolysaccharide (LPS)-induced depression-like mouse model. C57BL/6 mice were randomly divided into four groups and treated with 5 mg/kg LPS via intraperitoneal injection to induce depression-like symptoms, followed by oral administration of LL95 for one week (1 × 109 CFU/mouse). The animals were then subjected to a series of behavioral assessments, including open field, sucrose preference, and forced swimming tests. In addition, we evaluated the levels of reactive oxygen species, tumor necrosis factor-α, and interleukin-1β in the hippocampal tissues of these animals, and also determined their fecal lactic acid bacteria (LAB) content. LL95 intervention improved LPS-induced depression-like behaviors in mice, including decreased sucrose preference and increased immobility time in the forced swim test. LL95 treatment reversed the LPS-induced increase in hippocampal levels of reactive oxygen species and tumor necrosis factor-α, and of interleukin-1β to a lesser extent. Furthermore, LL95 intervention increased the fecal LAB content in these animals, suggesting changes in the gut microbiota. These findings suggest that LL95 exerts antidepressant-like effects in LPS-induced depression, which may be attributed to modulation of the oxidative status and pro-inflammatory cytokine expression in the hippocampus and alteration in the LAB content of the gut microbiota.
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Affiliation(s)
- Juliana Bernera Ramalho
- Laboratório de Estresse Oxidativo, Universidade Federal do Pampa (UNIPAMPA), Campus Uruguaiana, 97500-970 Uruguaiana, RS, Brazil
| | - Cristiano Chiapinotto Spiazzi
- Laboratório de Estresse Oxidativo, Universidade Federal do Pampa (UNIPAMPA), Campus Uruguaiana, 97500-970 Uruguaiana, RS, Brazil
| | - Diogo Ferreira Bicca
- Laboratório de Estresse Oxidativo, Universidade Federal do Pampa (UNIPAMPA), Campus Uruguaiana, 97500-970 Uruguaiana, RS, Brazil
| | - Jéssica Ferreira Rodrigues
- Laboratório de Estresse Oxidativo, Universidade Federal do Pampa (UNIPAMPA), Campus Uruguaiana, 97500-970 Uruguaiana, RS, Brazil
| | - Carla Pohl Sehn
- Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas (LaftamBio), Universidade Federal do Pampa (UNIPAMPA), Campus Itaqui, 97650-000 Itaqui, RS, Brazil
| | - Wladimir Padilha da Silva
- Departamento de Ciência e Tecnologia Agroindustrial (DCTA), Universidade Federal de Pelotas (UFPel), 96010-900 Pelotas, RS, Brazil
| | - Francielli Weber Santos Cibin
- Laboratório de Estresse Oxidativo, Universidade Federal do Pampa (UNIPAMPA), Campus Uruguaiana, 97500-970 Uruguaiana, RS, Brazil.
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11
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Zhang L, Xu Z, Mak JWY, Chow KM, Lui G, Li TCM, Wong CK, Chan PKS, Ching JYL, Fujiwara Y, Chan FKL, Ng SC. Gut microbiota-derived synbiotic formula (SIM01) as a novel adjuvant therapy for COVID-19: An open-label pilot study. J Gastroenterol Hepatol 2022; 37:823-831. [PMID: 35170078 PMCID: PMC9115073 DOI: 10.1111/jgh.15796] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Revised: 01/18/2022] [Accepted: 02/03/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIM Gut dysbiosis is associated with immune dysfunction and severity of COVID-19. Whether targeting dysbiosis will improve outcomes of COVID-19 is unknown. This study aimed to assess the effects of a novel gut microbiota-derived synbiotic formula (SIM01) as an adjuvant therapy on immunological responses and changes in gut microbiota of hospitalized COVID-19 patients. METHODS This was an open-label, proof-of-concept study. Consecutive COVID-19 patients admitted to an infectious disease referral center in Hong Kong were given a novel formula of Bifidobacteria strains, galactooligosaccharides, xylooligosaccharide, and resistant dextrin (SIM01). The latter was derived from metagenomic databases of COVID-19 patients and healthy population. COVID-19 patients who were admitted under another independent infectious disease team during the same period without receiving SIM01 acted as controls. All patients received standard treatments for COVID-19 according to the hospital protocol. We assessed antibody response, plasma proinflammatory markers, nasopharyngeal SARS-CoV-2 viral load, and fecal microbiota profile from admission up to week 5. RESULTS Twenty-five consecutive COVID-19 patients received SIM01 for 28 days; 30 patients who did not receive the formula acted as controls. Significantly more patients receiving SIM01 than controls developed SARS-CoV-2 IgG antibody (88% vs 63.3%; P = 0.037) by Day 16. One (4%) and 8 patients (26.7%) in the SIM01 and control group, respectively, failed to develop positive IgG antibody upon discharge. At week 5, plasma levels of interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), macrophage colony-stimulating factor (M-CSF), tumor necrosis factor (TNF-α), and IL-1RA reduced significantly in the SIM01 but not in the control group. There was a significant negative correlation of nasopharyngeal SARS-CoV-2 viral load and SIM01 intervention. Metagenomic analysis showed that bacterial species in SIM01 formula were found in greater abundance leading to enrichment of commensal bacteria and suppression of opportunistic pathogens in COVID-19 patients by week 4 and week 5. CONCLUSIONS This proof-of-concept study suggested that the use of a novel gut microbiota-derived synbiotic formula, SIM01, hastened antibody formation against SARS-CoV-2, reduced nasopharyngeal viral load, reduced pro-inflammatory immune markers, and restored gut dysbiosis in hospitalised COVID-19 patients.
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Affiliation(s)
- Lin Zhang
- Microbiota I‐Center (MagIC)The Chinese University of Hong KongHong Kong SARChina,Department of Medicine and Therapeutics, Faculty of MedicineThe Chinese University of Hong KongHong Kong SARChina,State Key Laboratory of Digestive Disease, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, Faculty of MedicineThe Chinese University of Hong KongHong Kong SARChina
| | - Zhilu Xu
- Microbiota I‐Center (MagIC)The Chinese University of Hong KongHong Kong SARChina,Department of Medicine and Therapeutics, Faculty of MedicineThe Chinese University of Hong KongHong Kong SARChina,State Key Laboratory of Digestive Disease, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, Faculty of MedicineThe Chinese University of Hong KongHong Kong SARChina
| | - Joyce W Y Mak
- Microbiota I‐Center (MagIC)The Chinese University of Hong KongHong Kong SARChina,Department of Medicine and Therapeutics, Faculty of MedicineThe Chinese University of Hong KongHong Kong SARChina,State Key Laboratory of Digestive Disease, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, Faculty of MedicineThe Chinese University of Hong KongHong Kong SARChina
| | - Kai Ming Chow
- Department of Medicine and Therapeutics, Faculty of MedicineThe Chinese University of Hong KongHong Kong SARChina
| | - Grace Lui
- Department of Medicine and Therapeutics, Faculty of MedicineThe Chinese University of Hong KongHong Kong SARChina,Stanley Ho Centre for Emerging Infectious Diseases, Faculty of MedicineThe Chinese University of Hong KongHong Kong SARChina
| | - Timothy C M Li
- Department of Medicine and Therapeutics, Faculty of MedicineThe Chinese University of Hong KongHong Kong SARChina
| | - Chun Kwok Wong
- Department of Chemical Pathology, Faculty of MedicineThe Chinese University of Hong KongHong Kong SARChina
| | - Paul K S Chan
- Department of Microbiology, Faculty of MedicineThe Chinese University of Hong KongHong Kong SARChina
| | - Jessica Y L Ching
- Department of Medicine and Therapeutics, Faculty of MedicineThe Chinese University of Hong KongHong Kong SARChina
| | - Yasuhiro Fujiwara
- Department of GastroenterologyOsaka City University Graduate School of MedicineOsakaJapan
| | - Francis K L Chan
- Microbiota I‐Center (MagIC)The Chinese University of Hong KongHong Kong SARChina,Department of Medicine and Therapeutics, Faculty of MedicineThe Chinese University of Hong KongHong Kong SARChina,State Key Laboratory of Digestive Disease, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, Faculty of MedicineThe Chinese University of Hong KongHong Kong SARChina
| | - Siew C Ng
- Microbiota I‐Center (MagIC)The Chinese University of Hong KongHong Kong SARChina,Department of Medicine and Therapeutics, Faculty of MedicineThe Chinese University of Hong KongHong Kong SARChina,State Key Laboratory of Digestive Disease, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, Faculty of MedicineThe Chinese University of Hong KongHong Kong SARChina
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12
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Javanshir N, Hosseini GNG, Sadeghi M, Esmaeili R, Satarikia F, Ahmadian G, Allahyari N. Evaluation of the Function of Probiotics, Emphasizing the Role of their Binding to the Intestinal Epithelium in the Stability and their Effects on the Immune System. Biol Proced Online 2021; 23:23. [PMID: 34847891 PMCID: PMC8903605 DOI: 10.1186/s12575-021-00160-w] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Accepted: 11/04/2021] [Indexed: 12/11/2022] Open
Abstract
Due to the importance of using cost-effective methods for therapeutic purposes, the function of probiotics as safe microorganisms and the study of their relevant functional mechanisms have recently been in the spotlight. Finding the mechanisms of attachment and stability and their beneficial effects on the immune system can be useful in identifying and increasing the therapeutic effects of probiotics. In this review, the functional mechanisms of probiotics were comprehensively investigated. Relevant articles were searched in scientific sources, documents, and databases, including PubMed, NCBI, Bactibace, OptiBac, and Bagel4. The most important functional mechanisms of probiotics and their effects on strengthening the epithelial barrier, competitive inhibition of pathogenic microorganisms, production of antimicrobials, binding and interaction with the host, and regulatory effects on the immune system were discussed. In this regard, the attachment of probiotics to the epithelium is very important because the prerequisite for their proper functioning is to establish a proper connection to the epithelium. Therefore, more attention should be paid to the binding effect of probiotics, including sortase A, a significant factor involved in the expression of sortase-dependent proteins (SDP), on their surface as mediators of intestinal epithelial cell binding. In general, by investigating the functional mechanisms of probiotics, it was concluded that the mechanism by which probiotics regulate the immune system and adhesion capacity can directly and indirectly have preventive and therapeutic effects on a wide range of diseases. However, further study of these mechanisms requires extensive research on various aspects.
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Affiliation(s)
- Nahid Javanshir
- Department of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology. (NIGEB), P.O. Box: 14155-6343, Tehran, Iran
| | | | - Mahdieh Sadeghi
- Department of Science, Islamic Azad University - Parand Branch, Parand, Iran
| | | | - Fateme Satarikia
- Department of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Gholamreza Ahmadian
- Department of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology. (NIGEB), P.O. Box: 14155-6343, Tehran, Iran.
| | - Najaf Allahyari
- Department of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology. (NIGEB), P.O. Box: 14155-6343, Tehran, Iran.
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13
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Luo X, Kong Q, Wang Y, Duan X, Wang P, Li C, Huan Y. Colonization of Clostridium butyricum in Rats and Its Effect on Intestinal Microbial Composition. Microorganisms 2021; 9:1573. [PMID: 34442652 PMCID: PMC8401576 DOI: 10.3390/microorganisms9081573] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 07/14/2021] [Accepted: 07/19/2021] [Indexed: 12/31/2022] Open
Abstract
Gut microorganisms participate in many physiological processes. In particular, Clostridium butyricum can modulate gut microorganisms and treat diseases. The colonization and persistence of strains in the gut contribute to beneficial effects, and the colonization by C. butyricum in the gut is currently unknown. We investigated the total intestinal contents of C. butyricum at 12 h, 24 h, 48 h, and four and six days using real-time reverse transcription-PCR, after oral administration of C. butyricum to rats for seven consecutive days. We assessed the bacterial community structure using Illumina MiSeq sequencing. The results showed that C. butyricum was mainly colonized in the colon. The total content of C. butyricum in the gut increased significantly at 12 h after administration. Exogenous C. butyricum could still be detected in the gut six days after administration. Administration of C. butyricum significantly enhanced gut microbial diversity. The relative abundance of short-chain fatty acid-producing bacterial genera was shown to be higher than that of the control group, and treatment with C. butyricum elevated Firmicutes and diminished Bacteroidetes phyla compared with to the control group. These findings laid the foundation for the study of probiotic colonization capacity and the improvement of microflora for the prevention of gut diseases.
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Affiliation(s)
| | - Qing Kong
- School of Food Science and Engineering, Ocean University of China, Qingdao 266003, China; (X.L.); (Y.W.); (X.D.); (P.W.); (C.L.); (Y.H.)
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14
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Jakobsen LMA, Sundekilde UK, Andersen HJ, Kot W, Mejia JLC, Nielsen DS, Hansen AK, Bertram HC. Administration of Bovine Milk Oligosaccharide to Weaning Gnotobiotic Mice Inoculated with a Simplified Infant Type Microbiota. Microorganisms 2021; 9:microorganisms9051003. [PMID: 34066501 PMCID: PMC8148552 DOI: 10.3390/microorganisms9051003] [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] [Received: 04/07/2021] [Revised: 04/22/2021] [Accepted: 05/04/2021] [Indexed: 12/18/2022] Open
Abstract
Bovine milk oligosaccharides (BMO) share structural similarity to selected human milk oligosaccharides, which are natural prebiotics for infants. Thus, there is a potential in including BMOs as a prebiotic in infant formula. To examine the in vivo effect of BMO-supplementation on the infant gut microbiota, a BMO-rich diet (2% w/w) was fed to gnotobiotic mice (n = 11) inoculated with an infant type co-culture and compared with gnotobiotic mice receiving a control diet (n = 9). Nuclear magnetic resonance metabolomics in combination with high-throughput 16S rRNA gene amplicon sequencing was used to compare metabolic activity and microbiota composition in different compartments of the lower gastrointestinal tract. BMO components were detected in cecum and colon contents, revealing that BMO was available for the gut bacteria. The gut microbiota was dominated by Enterobacteriaceae and minor abundance of Lactobacilliaceae, while colonization of Bifidobacteriaceae did not succeed. Apart from a lower E. coli population in cecum content and lower formate (in colon) and succinate (in colon and cecum) concentrations, BMO supplementation did not result in significant changes in microbiota composition nor metabolic activity. The present study corroborates the importance of the presence of bifidobacteria for obtaining microbial-derived effects of milk oligosaccharides in the gastrointestinal tract.
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Affiliation(s)
- Louise Margrethe Arildsen Jakobsen
- Department of Food Science, Aarhus University, Agro Food Park 48, 8200 Aarhus N, Denmark; (U.K.S.); (H.C.B.)
- Correspondence: ; Tel.: +45-2073-1316
| | - Ulrik Kræmer Sundekilde
- Department of Food Science, Aarhus University, Agro Food Park 48, 8200 Aarhus N, Denmark; (U.K.S.); (H.C.B.)
| | | | - Witold Kot
- Department of Plant and Environmental Sciences, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark;
| | - Josue Leonardo Castro Mejia
- Department of Food Science, University of Copenhagen, Rolighedsvej 30, 1958 Frederiksberg C, Denmark; (J.L.C.M.); (D.S.N.)
| | - Dennis Sandris Nielsen
- Department of Food Science, University of Copenhagen, Rolighedsvej 30, 1958 Frederiksberg C, Denmark; (J.L.C.M.); (D.S.N.)
| | - Axel Kornerup Hansen
- Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Grønnegårdsvej 17, 1870 Frederiksberg C, Denmark;
| | - Hanne Christine Bertram
- Department of Food Science, Aarhus University, Agro Food Park 48, 8200 Aarhus N, Denmark; (U.K.S.); (H.C.B.)
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Xiao Y, Zhai Q, Zhang H, Chen W, Hill C. Gut Colonization Mechanisms of Lactobacillus and Bifidobacterium: An Argument for Personalized Designs. Annu Rev Food Sci Technol 2021; 12:213-233. [DOI: 10.1146/annurev-food-061120-014739] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Lactobacillus and Bifidobacterium spp. are best understood for their applications as probiotics, which are often transient, but as commensals it is probable that stable colonization in the gut is important for their beneficial roles. Recent research suggests that the establishment and persistence of strains of Lactobacillus and Bifidobacterium in the gut are species- and strain-specific and affected by natural history, genomic adaptability, and metabolic interactions of the bacteria and the microbiome and immune aspects of the host but also regulated by diet. This provides new perspectives on the underlying molecular mechanisms. With an emphasis on host–microbe interaction, this review outlines how the characteristics of individual Lactobacillus and Bifidobacterium bacteria, the host genotype and microbiome structure,diet, and host–microbe coadaptation during bacterial gut transition determine and influence the colonization process. The diet-tuned and personally tailored colonization can be achieved via a machine learning prediction model proposed here.
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Affiliation(s)
- Yue Xiao
- State Key Laboratory of Food Science and Technology and School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China;, , ,
| | - Qixiao Zhai
- State Key Laboratory of Food Science and Technology and School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China;, , ,
- International Joint Research Laboratory for Probiotics, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Hao Zhang
- State Key Laboratory of Food Science and Technology and School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China;, , ,
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu 214122, China
- Institute of Food Biotechnology, Jiangnan University, Yangzhou, Jiangsu 225004, China
| | - Wei Chen
- State Key Laboratory of Food Science and Technology and School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China;, , ,
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu 214122, China
- Beijing Advanced Innovation Center of Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China
| | - Colin Hill
- School of Microbiology and APC Microbiome Institute, University College Cork, Cork T12 YN60, Ireland
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16
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Markey L, Pugliese A, Tian T, Roy F, Lee K, Kumamoto CA. Decreased Ecological Resistance of the Gut Microbiota in Response to Clindamycin Challenge in Mice Colonized with the Fungus Candida albicans. mSphere 2021; 6:e00982-20. [PMID: 33472981 PMCID: PMC7845615 DOI: 10.1128/msphere.00982-20] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Accepted: 12/18/2020] [Indexed: 02/06/2023] Open
Abstract
The mammalian gut microbiota is a complex community of microorganisms which typically exhibits remarkable stability. As the gut microbiota has been shown to affect many aspects of host health, the molecular keys to developing and maintaining a "healthy" gut microbiota are highly sought after. Yet, the qualities that define a microbiota as healthy remain elusive. We used the ability to resist change in response to antibiotic disruption, a quality we refer to as ecological resistance, as a metric for the health of the bacterial microbiota. Using a mouse model, we found that colonization with the commensal fungus Candida albicans decreased the ecological resistance of the bacterial microbiota in response to the antibiotic clindamycin such that increased microbiota disruption was observed in C. albicans-colonized mice compared to that in uncolonized mice. C. albicans colonization resulted in decreased alpha diversity and small changes in abundance of bacterial genera prior to clindamycin challenge. Strikingly, co-occurrence network analysis demonstrated that C. albicans colonization resulted in sweeping changes to the co-occurrence network structure, including decreased modularity and centrality and increased density. Thus, C. albicans colonization resulted in changes to the bacterial microbiota community and reduced its ecological resistance.IMPORTANCECandida albicans is the most common fungal member of the human gut microbiota, yet its ability to interact with and affect the bacterial gut microbiota is largely uncharacterized. Previous reports showed limited changes in microbiota composition as defined by bacterial species abundance as a consequence of C. albicans colonization. We also observed only a few bacterial genera that were significantly altered in abundance in C. albicans-colonized mice; however, C. albicans colonization significantly changed the structure of the bacterial microbiota co-occurrence network. Additionally, C. albicans colonization changed the response of the bacterial microbiota ecosystem to a clinically relevant perturbation, challenge with the antibiotic clindamycin.
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Affiliation(s)
- Laura Markey
- Graduate School of Biomedical Sciences, Tufts University School of Medicine, Boston, Massachusetts, USA
- Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA
| | - Antonia Pugliese
- Graduate School of Biomedical Sciences, Tufts University School of Medicine, Boston, Massachusetts, USA
- Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA
| | - Theresa Tian
- Department of Chemical and Biological Engineering, Tufts University School of Engineering, Medford, Massachusetts, USA
| | - Farrah Roy
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Kyongbum Lee
- Department of Chemical and Biological Engineering, Tufts University School of Engineering, Medford, Massachusetts, USA
| | - Carol A Kumamoto
- Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA
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17
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Hui Y, Smith B, Mortensen MS, Krych L, Sørensen SJ, Greisen G, Krogfelt KA, Nielsen DS. The effect of early probiotic exposure on the preterm infant gut microbiome development. Gut Microbes 2021; 13:1951113. [PMID: 34264803 PMCID: PMC8284123 DOI: 10.1080/19490976.2021.1951113] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 05/17/2021] [Accepted: 06/24/2021] [Indexed: 02/04/2023] Open
Abstract
Premature birth, especially if born before week 32 of gestation, is associated with increased risk of neonatal morbidity and mortality. Prophylactic use of probiotics has been suggested to protect preterm infants via supporting a healthy gut microbiota (GM) development, but the suggested strains and doses vary between studies. In this study, we profiled the GM of 5, 10 and 30-day fecal samples from two cohorts of preterm neonates (born <30 weeks of gestation) recruited in the same neonatal intensive care unit. One cohort (n = 165) was recruited from September 2006 to January 2009 before probiotics were introduced in the clinic. The second cohort (n = 87) was recruited from May 2010 to October 2011 after introducing Lacticaseibacillus rhamnosus GG and Bifidobacterium animalis ssp. lactis BB-12 supplementation policy. Through V3-V4 region 16S rRNA gene amplicon sequencing, a distinct increase of L. rhamnosus and B. animalis was found in the fecal samples of neonates supplemented with probiotics. During the first 30 days of life, the preterm GM went through similarly patterned progression of bacterial populations. Staphylococcus and Weissella dominated in early samples, but was gradually overtaken by Veillonella, Enterococcus and Enterobacteriaceae. Probiotic supplementation was associated with pronounced reduction of Weissella, Veillonella spp. and the opportunistic pathogen Klebsiella. Potential nosocomial pathogens Citrobacter and Chryseobacterium species also gradually phased out. In conclusion, probiotic supplementation to preterm neonates affected gut colonization by certain bacteria, but did not change the overall longitudinal bacterial progression in the neonatal period.Abbreviations: GM: Gut microbiota; ASV: Amplicon sequence variant; NEC: Necrotizing enterocolitis; DOL: Days of life; NICU: Neonatal intensive care unit; ESPGHAN: European Society for Pediatric Gastroenterology, Hepatology and Nutrition; Db-RDA: Distance-based redundancy analysis; PERMANOVA: Permutational multivariate analysis of variance; ANCOM: Analysis of compositions of microbiomes; LGG: Lacticaseibacillus (former Lactobacillus) rhamnosus GG; BB-12: Bifidobacterium animalis ssp. lactis BB-12; DGGE: Denaturing Gradient Gel Electrophoresis.
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Affiliation(s)
- Yan Hui
- Department of Food Science, Faculty of Science, University of Copenhagen, Frederiksberg, Denmark
| | - Birgitte Smith
- Department of Pediatrics, Hvidovre Hospital, Hvidovre, Denmark
- Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Copenhagen, Denmark
| | | | - Lukasz Krych
- Department of Food Science, Faculty of Science, University of Copenhagen, Frederiksberg, Denmark
| | - Søren J. Sørensen
- Department of Biology, University of Copenhagen, Copenhagen, Denmark
| | - Gorm Greisen
- Department of Neonatology, Rigshospitalet,University of Copenhagen, Copenhagen, Denmark
| | - Karen Angeliki Krogfelt
- Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Copenhagen, Denmark
- Department of Science and Environment, Roskilde University, Roskilde, Denmark
| | - Dennis Sandris Nielsen
- Department of Food Science, Faculty of Science, University of Copenhagen, Frederiksberg, Denmark
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Kiu R, Treveil A, Harnisch LC, Caim S, Leclaire C, van Sinderen D, Korcsmaros T, Hall LJ. Bifidobacterium breve UCC2003 Induces a Distinct Global Transcriptomic Program in Neonatal Murine Intestinal Epithelial Cells. iScience 2020; 23:101336. [PMID: 32683312 PMCID: PMC7371750 DOI: 10.1016/j.isci.2020.101336] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Revised: 06/05/2020] [Accepted: 06/30/2020] [Indexed: 12/19/2022] Open
Abstract
The underlying health-driving mechanisms of Bifidobacterium during early life are not well understood, particularly how this microbiota member may modulate the intestinal barrier via programming of intestinal epithelial cells (IECs). We investigated the impact of Bifidobacterium breve UCC2003 on the transcriptome of neonatal murine IECs. Small IECs from two-week-old neonatal mice administered B. breve UCC2003 or PBS (control) were subjected to global RNA sequencing, and differentially expressed genes, pathways, and affected cell types were determined. We observed extensive regulation of the IEC transcriptome with ∼4,000 genes significantly up-regulated, including key genes linked with epithelial barrier function. Enrichment of cell differentiation pathways was observed, along with an overrepresentation of stem cell marker genes, indicating an increase in the regenerative potential of the epithelial layer. In conclusion, B. breve UCC2003 plays a central role in driving intestinal epithelium homeostatic development during early life and suggests future avenues for next-stage clinical studies.
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Affiliation(s)
- Raymond Kiu
- Gut Microbes & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich NR4 7UQ, UK
| | - Agatha Treveil
- Gut Microbes & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich NR4 7UQ, UK; Earlham Institute, Norwich Research Park, Norwich NR4 7UZ, UK
| | - Lukas C Harnisch
- Gut Microbes & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich NR4 7UQ, UK
| | - Shabhonam Caim
- Gut Microbes & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich NR4 7UQ, UK
| | - Charlotte Leclaire
- Gut Microbes & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich NR4 7UQ, UK
| | - Douwe van Sinderen
- APC Microbiome Ireland & School of Microbiology, University College Cork, Cork T12YT20, Ireland
| | - Tamas Korcsmaros
- Gut Microbes & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich NR4 7UQ, UK; Earlham Institute, Norwich Research Park, Norwich NR4 7UZ, UK
| | - Lindsay J Hall
- Gut Microbes & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich NR4 7UQ, UK; Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK; Chair of Intestinal Microbiome, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany; ZIEL - Institute for Food & Health, Technical University of Munich, 85354 Freising, Germany.
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Administration of Bifidobacterium bifidum CGMCC 15068 modulates gut microbiota and metabolome in azoxymethane (AOM)/dextran sulphate sodium (DSS)-induced colitis-associated colon cancer (CAC) in mice. Appl Microbiol Biotechnol 2020; 104:5915-5928. [PMID: 32367312 DOI: 10.1007/s00253-020-10621-z] [Citation(s) in RCA: 51] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2019] [Revised: 03/31/2020] [Accepted: 04/09/2020] [Indexed: 12/31/2022]
Abstract
The gut microbiota plays an important role in colorectal cancer (CRC), and the use of probiotics might be a promising intervention method. The aim of our study was to investigate the beneficial effect of Bifidobacterium bifidum CGMCC 15068 on an azoxymethane (AOM)/dextran sulphate sodium (DSS)-induced colitis-associated CRC (CAC) mouse model. CAC was induced by an intra-peritoneal injection of AOM (10 mg/kg) and three 7-day cycles of 2% DSS in drinking water with a 14-day recovery period between two consecutive DSS administrations. B. bifidum CGMCC 15068 (3 × 109 CFU/mL) was gavaged once daily during the recovery period. Then, the faecal microbial composition and metabolome were profiled using the 16S rRNA sequencing technology and gas chromatography-mass spectrometry (GC-MS), respectively. The administration of B. bifidum CGMCC 15068 attenuated tumourigenesis in the CAC mouse model. In addition, B. bifidum CGMCC 15068 pre-treatment increased the relative abundance of Akkermansia, Desulfovibrionaceae, Romboutsia, Turicibacter, Verrucomicrobiaceae, Ruminococcaceae_UCG_013, Lachnospiraceae_UCG_004, and Lactobacillus. Meanwhile, B. bifidum CGMCC 15068 altered metabolites involved in the citrate cycle (TCA cycle), glycolysis, butyrate metabolism, fatty acid biosynthesis, and galactose metabolism. Several significant correlations were identified between the differentially abundant microbes and metabolites. These findings supported the beneficial role of B. bifidum CGMCC 15068 in intestinal health by modulating dysbiosis and the gut metabolic profile. The manipulation of the gut microbial composition using probiotics might be a promising prevention strategy for CRC. Long-term and large-scale clinical trials are warranted for the potential clinical applications of this strategy in the future.
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Chemopreventive Effect of the Germinated Oat and its Phenolic-AVA Extract in Azoxymethane/Dextran Sulfate Sodium (AOM/DSS) Model of Colon Carcinogenesis in Mice. Foods 2020; 9:foods9020169. [PMID: 32050698 PMCID: PMC7074527 DOI: 10.3390/foods9020169] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 02/06/2020] [Accepted: 02/06/2020] [Indexed: 12/11/2022] Open
Abstract
The consumption of fruits, vegetables, nuts, legumes, and whole grains has been associated with a lower risk of colorectal cancer (CRC) due to the content of natural compounds with antioxidant and anticancer activities. The oat (Avena sativa L.) is a unique source of avenanthramides (AVAs), among other compounds, with chemopreventive effects. In addition, oat germination has shown enhanced nutraceutical and phytochemical properties. Therefore, our objective was to evaluate the chemopreventive effect of the sprouted oat (SO) and its phenolic-AVA extract (AVA) in azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CRC mouse model. Turquesa oat seeds were germinated (five days at 25 °C and 60% relative humidity) and, after 16 weeks of administration, animals in the SO- and AVA-treated groups had a significantly lower inflammation grade and tumor (38–50%) and adenocarcinoma (38–63%) incidence compared to those of the AOM+DSS group (80%). Although both treatments normalized colonic GST and NQO1 activities as well as erythrocyte GSH levels, and significantly reduced cecal and colonic β-GA, thus indicating an improvement in the intestinal parameters, the inflammatory states, and the redox states of the animals, SO exerted a superior chemopreventive effect, probably due to the synergistic effects of multiple compounds. Our results indicate that oats retain their biological properties even after the germination process.
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21
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Qu X, Li Q, Song Y, Xue A, Liu Y, Qi D, Dong H. Potential of myricetin to restore the immune balance in dextran sulfate sodium-induced acute murine ulcerative colitis. J Pharm Pharmacol 2019; 72:92-100. [PMID: 31724745 DOI: 10.1111/jphp.13197] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Accepted: 10/21/2019] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Myricetin is a bioactive compound in many edible plants with anti-inflammatory and anticarcinogenic activity. The current study aimed to determine the protective effects and mechanism of myricetin against ulcerative colitis (UC). METHODS Myricetin was orally administered at doses of 40 and 80 mg/kg to C57BL/6 mice with UC induced using dextran sulfate sodium. The disease-associated index and colon length were determined at the end of the experiment, the proportion of Treg, Th1 and Th17 was analysed by cytometry, and cytokines were detected using ELISA. KEY FINDINGS Myricetin (80 mg/kg) ameliorated the severity of inflammation in acute UC and significantly improved the condition. Myricetin (80 mg/kg) elevated the levels of IL-10 and transforming growth factor β. In addition, the proportion of regulatory T cells significantly increased in mice in the myricetin treatment group. CONCLUSIONS Taking together, these results suggest that myricetin exhibits significant protective effects against UC and it could be used as a potential treatment for UC.
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Affiliation(s)
- Xinyan Qu
- Laboratory of Immunology for Environment and Health, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Shandong, China
| | - Qingjun Li
- Experimental Center, Shandong University of Traditional Chinese Medicine, Shandong, China.,Key Laboratory of Basic Research of Traditional Chinese Medicine in Shandong Province, Shandong, China
| | - Yue Song
- Laboratory of Immunology for Environment and Health, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Shandong, China
| | - Anqi Xue
- Laboratory of Immunology for Environment and Health, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Shandong, China
| | - Yuhua Liu
- Laboratory of Immunology for Environment and Health, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Shandong, China
| | - Dongmei Qi
- Experimental Center, Shandong University of Traditional Chinese Medicine, Shandong, China.,Key Laboratory of Basic Research of Traditional Chinese Medicine in Shandong Province, Shandong, China
| | - Hongjing Dong
- Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Shandong, China
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22
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Oral Administration of Microencapsulated B. Longum BAA-999 and Lycopene Modulates IGF-1/IGF-1R/IGFBP3 Protein Expressions in a Colorectal Murine Model. Int J Mol Sci 2019; 20:ijms20174275. [PMID: 31480481 PMCID: PMC6747182 DOI: 10.3390/ijms20174275] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Revised: 08/24/2019] [Accepted: 08/29/2019] [Indexed: 01/09/2023] Open
Abstract
The Insulin-like growth factor-I/Insulin-like growth factor-I receptor (IGF-1/IGF-1R) system is a major determinant in colorectal cancer (CRC) pathogenesis. Probiotics (Bifidobacterium longum, BF) and lycopene (LYC) have been individually researched for their beneficial effects in the prevention of CRC. However, the effect of a combined treatment of microencapsulated BF and LYC on IGF-1/IGF-1R/IGFBPs (Insulin-like growth factor-binding proteins) expression in an azoxymethane (AOM)-dextran sulfate sodium (DSS)-induced CRC model have not been demonstrated. BF was microencapsulated by the spray drying technique, with high viability, and daily gavaged with LYC for 16 weeks to CD-1 mice in an AOM-DSS model. The results indicated that BF- and BF + LYC-treated groups had significantly lower inflammation grade, tumor incidence (13–38%) and adenocarcinoma (13–14%) incidence compared to the AOM + DSS group (80%), whereas LYC treatment only protected against inflammation grade and incidence. Caecal, colonic and fecal pH and β-glucuronidase (β-GA) values were significantly normalized by BF and LYC. Similarly, BF and BF + LYC treatments significantly reduced both the positive rate and expression grade of IGF-1 and IGF-1R proteins and normalized Insulin-like growth factor-binding protein-3 (IGFBP3) expression. Based on intestinal parameters related to the specific colon carcinogenesis in an AOM-DSS-induced model, LYC and microencapsulated BF supplementation resulted in a significant chemopreventive potential through the modulation of IGF-1/IGF-1R system.
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23
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Mining Lactobacillus and Bifidobacterium for organisms with long-term gut colonization potential. Clin Nutr 2019; 39:1315-1323. [PMID: 31174942 DOI: 10.1016/j.clnu.2019.05.014] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2019] [Revised: 05/01/2019] [Accepted: 05/17/2019] [Indexed: 11/20/2022]
Abstract
Probiotics administered orally endure one of two fates: some merely pass through, but others colonize the gut permanently. Although probiotics that can stably engraft in the gut are believed to exert beneficial effects on the host in terms of increasing the efficiency of metabolic activity and enabling durable modulation of the indigenous microbiota, the strains of long-term gut colonizers are poorly delineated. This review summarizes the gut colonization modes of Lactobacillus and Bifidobacterium in the context of their natural niches and engraftment metadata in an attempt to identify organisms with long-term gut colonization potential. Advances in colonization evaluation methods are identified, and the effects of dietary components and metabolic interactions among ingested strains on bacterial colonization are discussed.
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24
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In Vitro Probiotic and Antioxidant Potential of Lactococcus lactis subsp. cremoris LL95 and Its Effect in Mice Behaviour. Nutrients 2019; 11:nu11040901. [PMID: 31013601 PMCID: PMC6521076 DOI: 10.3390/nu11040901] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Revised: 04/01/2019] [Accepted: 04/03/2019] [Indexed: 12/19/2022] Open
Abstract
The composition of intestinal microbiota is widely believed to not only affect gut health but also influence behaviour. This study aimed to evaluate the probiotic characteristics, antioxidant activity, and antidepressant- and anxiolytic-like activities of Lactococcus lactis subsp. cremoris LL95. This strain showed probiotic properties such as resistance in a simulated gastric tract model and survival at different concentrations of NaCl and bile salts. Moreover, antioxidant activity of LL95 was demonstrated through DPPH radical scavenging activity, scavenging of ABTS•+ radical and ferric ion reducing antioxidant power (FRAP) assays. Female C57BL/6 mice received LL95 orally at a dose of 109 UFC/day for 28 days. LL95 improved depressive- and anxiety-like behaviour, demonstrated by decreased immobility time in the tail suspension test and forced swim test and increased per cent of time spent in the open arms on the elevated plus maze. These findings indicate the potential antioxidant activity of LL95 and its role in behaviour, suggesting that probiotic may have therapeutic applications.
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25
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26
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Misic AM, Miedel EL, Brice AK, Cole S, Zhang GF, Dyer CD, Secreto A, Smith AL, Danet-Desnoyers G, Beiting DP. Culture-independent Profiling of the Fecal Microbiome to Identify Microbial Species Associated with a Diarrheal Outbreak in Immunocompromised Mice. Comp Med 2018; 68:261-268. [PMID: 29898804 DOI: 10.30802/aalas-cm-17-000084] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Immunocompromised mice are used frequently in biomedical research, in part because they accommodate the engraftment and study of primary human cells within a mouse model; however, these animals are susceptible to opportunistic infections and require special husbandry considerations. In 2015, an outbreak marked by high morbidity but low mortality swept through a colony of immunocompromised mice; this outbreak rapidly affected 75% of the colony and ultimately required complete depopulation of the barrier suite. Conventional microbiologic and molecular diagnostics were unsuccessful in determining the cause; therefore, we explored culture-independent methods to broadly profile the microbial community in the feces of affected animals. This approach identified 4 bacterial taxa- Candidatus Arthromitus, Clostridium celatum, Clostridiales bacterium VE202-01, and Bifidobacterium pseudolongum strain PV8-2- that were significantly enriched in the affected mice. Based on these results, specific changes were made to the animal husbandry procedures for immunocompromised mice. This case report highlights the utility of culture-independent methods in laboratory animal diagnostics.
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Affiliation(s)
- Ana M Misic
- Department of Pathobiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Emily L Miedel
- Comparative Medicine, University of South Florida, Tampa, Florida, USA
| | - Angela K Brice
- Department of Pathobiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Comparative Medicine, University of South Florida, Tampa, Florida, USA
| | - Stephen Cole
- Department of Pathobiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Grace F Zhang
- Department of Pathobiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Cecilia D Dyer
- Comparative Medicine, University of South Florida, Tampa, Florida, USA
| | - Anthony Secreto
- Stem Cell and Xenograft Core, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Abigail L Smith
- Department of Pathobiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Comparative Medicine, University of South Florida, Tampa, Florida, USA
| | - Gwenn Danet-Desnoyers
- Stem Cell and Xenograft Core, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Daniel P Beiting
- Department of Pathobiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
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27
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Martín R, Chain F, Miquel S, Motta JP, Vergnolle N, Sokol H, Langella P. Using murine colitis models to analyze probiotics-host interactions. FEMS Microbiol Rev 2018; 41:S49-S70. [PMID: 28830096 DOI: 10.1093/femsre/fux035] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2017] [Accepted: 06/08/2017] [Indexed: 02/07/2023] Open
Abstract
Probiotics are defined as 'live microorganisms which when administered in adequate amounts confer a health benefit on the host'. So, to consider a microorganism as a probiotic, a demonstrable beneficial effect on the health host should be shown as well as an adequate defined safety status and the capacity to survive transit through the gastrointestinal tract and to storage conditions. In this review, we present an overview of the murine colitis models currently employed to test the beneficial effect of the probiotic strains as well as an overview of the probiotics already tested. Our aim is to highlight both the importance of the adequate selection of the animal model to test the potential probiotic strains and of the value of the knowledge generated by these in vivo tests.
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Affiliation(s)
- Rebeca Martín
- INRA, Commensals and Probiotics-Host Interactions Laboratory, Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France
| | - Florian Chain
- INRA, Commensals and Probiotics-Host Interactions Laboratory, Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France
| | - Sylvie Miquel
- Laboratoire Microorganismes: Génome et Environnement (LMGE), UMR CNRS 6023, Université Clermont-Auvergne, 63000 Clermont-Ferrand, France
| | - Jean-Paul Motta
- Department of Biological Science, Inflammation Research Network, University of Calgary, AB T3E 4N1, Canada.,IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, F-31300 Toulouse, France
| | - Nathalie Vergnolle
- IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, F-31300 Toulouse, France
| | - Harry Sokol
- INRA, Commensals and Probiotics-Host Interactions Laboratory, Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France.,Sorbonne University - Université Pierre et Marie Curie (UPMC), 75252 Paris, France.,Institut National de la Santé et de la Recherche Médicale (INSERM) Equipe de Recherche Labélisée (ERL) 1157, Avenir Team Gut Microbiota and Immunity, 75012 Paris, France.,Department of Gastroenterology, Saint Antoine Hospital, Assistance Publique - Hopitaux de Paris, UPMC, 75012 Paris, France
| | - Philippe Langella
- INRA, Commensals and Probiotics-Host Interactions Laboratory, Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France
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28
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Exploring the role of the microbiota member Bifidobacterium in modulating immune-linked diseases. Emerg Top Life Sci 2017; 1:333-349. [PMID: 33525778 PMCID: PMC7288987 DOI: 10.1042/etls20170058] [Citation(s) in RCA: 73] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2017] [Revised: 10/22/2017] [Accepted: 10/25/2017] [Indexed: 12/19/2022]
Abstract
The gut-associated microbiota is essential for multiple physiological processes, including immune development. Acquisition of our initial pioneer microbial communities, including the dominant early life genus Bifidobacterium, occurs at a critical period of immune maturation and programming. Bifidobacteria are resident microbiota members throughout our lifetime and have been shown to modulate specific immune cells and pathways. Notably, reductions in this genus have been associated with several diseases, including inflammatory bowel disease. In this review, we provide an overview of bifidobacteria profiles throughout life and how different strains of bifidobacteria have been implicated in immune modulation in disease states. The focus will be examining preclinical models and outcomes from clinical trials on immune-linked chronic conditions. Finally, we highlight some of the important unresolved questions in relation to Bifidobacterium-mediated immune modulation and implications for future directions, trials, and development of new therapies.
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29
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Colliou N, Ge Y, Sahay B, Gong M, Zadeh M, Owen JL, Neu J, Farmerie WG, Alonzo F, Liu K, Jones DP, Li S, Mohamadzadeh M. Commensal Propionibacterium strain UF1 mitigates intestinal inflammation via Th17 cell regulation. J Clin Invest 2017; 127:3970-3986. [PMID: 28945202 PMCID: PMC5663347 DOI: 10.1172/jci95376] [Citation(s) in RCA: 61] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2017] [Accepted: 08/02/2017] [Indexed: 12/21/2022] Open
Abstract
Consumption of human breast milk (HBM) attenuates the incidence of necrotizing enterocolitis (NEC), which remains a leading and intractable cause of mortality in preterm infants. Here, we report that this diminution correlates with alterations in the gut microbiota, particularly enrichment of Propionibacterium species. Transfaunation of microbiota from HBM-fed preterm infants or a newly identified and cultured Propionibacterium strain, P. UF1, to germfree mice conferred protection against pathogen infection and correlated with profound increases in intestinal Th17 cells. The induction of Th17 cells was dependent on bacterial dihydrolipoamide acetyltransferase (DlaT), a major protein expressed on the P. UF1 surface layer (S-layer). Binding of P. UF1 to its cognate receptor, SIGNR1, on dendritic cells resulted in the regulation of intestinal phagocytes. Importantly, transfer of P. UF1 profoundly mitigated induced NEC-like injury in neonatal mice. Together, these results mechanistically elucidate the protective effects of HBM and P. UF1-induced immunoregulation, which safeguard against proinflammatory diseases, including NEC.
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Affiliation(s)
- Natacha Colliou
- Department of Infectious Diseases and Immunology
- Division of Gastroenterology, Hepatology & Nutrition, Department of Medicine
| | - Yong Ge
- Department of Infectious Diseases and Immunology
- Division of Gastroenterology, Hepatology & Nutrition, Department of Medicine
| | - Bikash Sahay
- Department of Infectious Diseases and Immunology
| | - Minghao Gong
- Department of Infectious Diseases and Immunology
- Division of Gastroenterology, Hepatology & Nutrition, Department of Medicine
| | - Mojgan Zadeh
- Department of Infectious Diseases and Immunology
- Division of Gastroenterology, Hepatology & Nutrition, Department of Medicine
| | | | - Josef Neu
- Division of Neonatology, Department of Pediatrics, and
| | - William G. Farmerie
- Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, Florida, USA
| | - Francis Alonzo
- Department of Microbiology and Immunology, Loyola University Chicago, Maywood, Illinois, USA
| | - Ken Liu
- Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Dean P. Jones
- Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Shuzhao Li
- Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Mansour Mohamadzadeh
- Department of Infectious Diseases and Immunology
- Division of Gastroenterology, Hepatology & Nutrition, Department of Medicine
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30
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A Commensal Bifidobacterium longum Strain Prevents Gluten-Related Immunopathology in Mice through Expression of a Serine Protease Inhibitor. Appl Environ Microbiol 2017; 83:AEM.01323-17. [PMID: 28778891 DOI: 10.1128/aem.01323-17] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2017] [Accepted: 07/27/2017] [Indexed: 02/07/2023] Open
Abstract
Microbiota-modulating strategies, including probiotic administration, have been tested for the treatment of chronic gastrointestinal diseases despite limited information regarding their mechanisms of action. We previously demonstrated that patients with active celiac disease have decreased duodenal expression of elafin, a human serine protease inhibitor, and supplementation of elafin by a recombinant Lactococcus lactis strain prevents gliadin-induced immunopathology in the NOD/DQ8 mouse model of gluten sensitivity. The commensal probiotic strain Bifidobacterium longum NCC2705 produces a serine protease inhibitor (Srp) that exhibits immune-modulating properties. Here, we demonstrate that B. longum NCC2705, but not a srp knockout mutant, attenuates gliadin-induced immunopathology and impacts intestinal microbial composition in NOD/DQ8 mice. Our results highlight the beneficial effects of a serine protease inhibitor produced by commensal B. longum strains.IMPORTANCE Probiotic therapies have been widely used to treat gastrointestinal disorders with variable success and poor mechanistic insight. Delivery of specific anti-inflammatory molecules has been limited to the use of genetically modified organisms, which has raised some public and regulatory concerns. By examining a specific microbial product naturally expressed by a commensal bacterial strain, we provide insight into a mechanistic basis for the use of B. longum NCC2705 to help treat gluten-related disorders.
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31
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Walter J, Maldonado-Gómez MX, Martínez I. To engraft or not to engraft: an ecological framework for gut microbiome modulation with live microbes. Curr Opin Biotechnol 2017; 49:129-139. [PMID: 28866242 DOI: 10.1016/j.copbio.2017.08.008] [Citation(s) in RCA: 122] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2017] [Revised: 08/08/2017] [Accepted: 08/14/2017] [Indexed: 02/08/2023]
Abstract
Strategies aimed at modulating the gut microbiota by using live microbes range from single strains (probiotics or live biotherapeutics) to whole non-defined fecal transplants. Although often clinically efficacious, our understanding on how microbial-based strategies modulate gut microbiome composition and function is vastly incomplete. In this review, we present a framework based on ecological theory that provides mechanistic explanations for the findings obtained in studies that attempted to modulate the gut microbiota of humans and animals using live microbes. We argue that an ecological perspective grounded in theory is necessary to interpret and predict the impact of microbiome-modulating strategies and thus advance our ability to develop improved and targeted approaches with enhanced therapeutic efficiency.
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Affiliation(s)
- Jens Walter
- Department of Agricultural, Food, and Nutritional Science, University of Alberta, AB, Canada; Department of Biological Sciences, University of Alberta, AB, Canada.
| | - María X Maldonado-Gómez
- Department of Food Science and Technology, University of California, Davis 95616, United States
| | - Inés Martínez
- Department of Agricultural, Food, and Nutritional Science, University of Alberta, AB, Canada; Sacco System, Cadorago 22071, Italy
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32
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Eichele DD, Kharbanda KK. Dextran sodium sulfate colitis murine model: An indispensable tool for advancing our understanding of inflammatory bowel diseases pathogenesis. World J Gastroenterol 2017; 23:6016-6029. [PMID: 28970718 PMCID: PMC5597494 DOI: 10.3748/wjg.v23.i33.6016] [Citation(s) in RCA: 565] [Impact Index Per Article: 70.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2017] [Revised: 07/07/2017] [Accepted: 08/01/2017] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are complex diseases that result from the chronic dysregulated immune response in the gastrointestinal tract. The exact etiology is not fully understood, but it is accepted that it occurs when an inappropriate aggressive inflammatory response in a genetically susceptible host due to inciting environmental factors occurs. To investigate the pathogenesis and etiology of human IBD, various animal models of IBD have been developed that provided indispensable insights into the histopathological and morphological changes as well as factors associated with the pathogenesis of IBD and evaluation of therapeutic options in the last few decades. The most widely used experimental model employs dextran sodium sulfate (DSS) to induce epithelial damage. The DSS colitis model in IBD research has advantages over other various chemically induced experimental models due to its rapidity, simplicity, reproducibility and controllability. In this manuscript, we review the newer publicized advances of research in murine colitis models that focus upon the disruption of the barrier function of the intestine, effects of mucin on the development of colitis, alterations found in microbial balance and resultant changes in the metabolome specifically in the DSS colitis murine model and its relation to the pathogenesis of IBD.
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Affiliation(s)
- Derrick D Eichele
- Department of Internal Medicine, Nebraska Medical Center, Omaha, NE 68198, United States
| | - Kusum K Kharbanda
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, United States
- Department of Internal Medicine, Nebraska Medical Center, Omaha, NE 68198, United States
- Department of Biochemistry and Molecular Biology, Nebraska Medical Center, Omaha, NE 68198, United States
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33
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Zachariassen LF, Krych L, Engkilde K, Nielsen DS, Kot W, Hansen CHF, Hansen AK. Sensitivity to oxazolone induced dermatitis is transferable with gut microbiota in mice. Sci Rep 2017; 7:44385. [PMID: 28290517 PMCID: PMC5349591 DOI: 10.1038/srep44385] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2016] [Accepted: 02/07/2017] [Indexed: 12/15/2022] Open
Abstract
Atopic Dermatitis (AD) has been associated with gut microbiota (GM) dysbiosis in humans, indicating a causative role of GM in AD etiology. Furthermore, the GM strongly correlates to essential disease parameters in the well-known oxazolone-induced mouse model of AD. Here, we demonstrate that it is possible to transfer both a high-responding and a low-responding AD phenotype with GM from conventional mice to germ-free mice. The mice inoculated with the high-responding GM had significantly higher clinical score, increased ear thickness, and increased levels of IL-1β, TNFα, IL-4, IL-5, and IL-6 compared to the mice inoculated with the low-responding GM. The inter-individual variation was in general not affected by this increase in effect size. Germ-free mice induced with AD revealed a high disease response as well as high inter-individual variation indicating protective properties of certain microbial taxa in this model. This study underlines that the GM has a strong impact on AD in mouse models, and that the power of studies may be increased by the application of mice inoculated with a specific GM from high responders to increase the effect size.
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Affiliation(s)
- Line Fisker Zachariassen
- Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
| | - Lukasz Krych
- Department of Food Science, Faculty of Science, University of Copenhagen, Denmark
| | - Kåre Engkilde
- The Bartholin Institute, Rigshospitalet, Copenhagen, Denmark
| | | | - Witold Kot
- Department of Environmental Science, Faculty of Science and Technology, Aarhus University, Denmark
| | - Camilla Hartmann Friis Hansen
- Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
| | - Axel Kornerup Hansen
- Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
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34
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Kang GD, Kim DH. Poncirin and its metabolite ponciretin attenuate colitis in mice by inhibiting LPS binding on TLR4 of macrophages and correcting Th17/Treg imbalance. JOURNAL OF ETHNOPHARMACOLOGY 2016; 189:175-185. [PMID: 27224242 DOI: 10.1016/j.jep.2016.05.044] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/15/2016] [Revised: 05/10/2016] [Accepted: 05/16/2016] [Indexed: 06/05/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The fruit of Poncirus trifoliate, which contains poncirin as a main constituent, is frequently used in the traditional Chinese medicine for inflammation, asthma, and infection diseases. AIM OF THE STUDY To examine anti-colitic effects of poncirin and ponciretin, a metabolite of poncirin by gut microbiota. MATERIALS AND METHODS Colitis was induced in mice by the intrarectal injection of 2,4,6-trinitrobenzenesulfonic acid (TNBS). Inflammatory markers were analyzed by enzyme-linked immunosorbent assay, immunoblotting, quantitative polymerase chain reaction, confocal microscopy, and flow cytometry. Peritoneal macrophages were isolated from mice stimulated with 4% thioglycolate. RESULTS Poncirin was metabolized to ponciretin in vitro and in vivo by gut microbiota of mice. Orally administered poncirin and ponciretin suppressed TNBS-induced colitis in mice: these inhibited colon shortening, myeloperoxidase activity, NF-κB activation, and Th17 cell differentiation, but increased occludin, claudin-1, and ZO-1 expressions and Treg cell differentiation. Poncirin and ponciretin suppressed the differentiation of splenocytes into Th17 cells and expression of IL-17 and Foxp3 in vitro, as well as the activation of macrophages stimulated with lipopolysaccharide (LPS) by inhibiting the binding of LPS on TLR4 of macrophages. These increased the differentiation of splenocytes into Treg cells. The ant-inflammatory effect of ponciretin was superior to that of poncirin. CONCLUSION Orally administered poncirin is metabolized to ponciretin by gut microbiota and poncirin and ponciretin attenuates colitis by suppressing NF-κB activation through the inhibition of LPS binding on macrophages and correcting Th17/Treg cell imbalance.
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MESH Headings
- Administration, Oral
- Animals
- Anti-Inflammatory Agents/administration & dosage
- Anti-Inflammatory Agents/metabolism
- Anti-Inflammatory Agents/pharmacology
- Bacteria/metabolism
- Biotransformation
- Cells, Cultured
- Colitis/chemically induced
- Colitis/immunology
- Colitis/metabolism
- Colitis/prevention & control
- Colon/drug effects
- Colon/immunology
- Colon/metabolism
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Drugs, Chinese Herbal/administration & dosage
- Drugs, Chinese Herbal/metabolism
- Drugs, Chinese Herbal/pharmacology
- Flavonoids/administration & dosage
- Flavonoids/metabolism
- Flavonoids/pharmacology
- Gastrointestinal Agents/administration & dosage
- Gastrointestinal Agents/metabolism
- Gastrointestinal Agents/pharmacology
- Gastrointestinal Microbiome
- Inflammation Mediators/metabolism
- Lipopolysaccharides/metabolism
- Lipopolysaccharides/pharmacology
- Macrophage Activation/drug effects
- Macrophages, Peritoneal/drug effects
- Macrophages, Peritoneal/immunology
- Macrophages, Peritoneal/metabolism
- Macrophages, Peritoneal/pathology
- Male
- Mice, Inbred C57BL
- NF-kappa B/metabolism
- Signal Transduction/drug effects
- Spleen/drug effects
- Spleen/immunology
- Spleen/metabolism
- T-Lymphocytes, Regulatory/drug effects
- T-Lymphocytes, Regulatory/immunology
- T-Lymphocytes, Regulatory/metabolism
- Th17 Cells/drug effects
- Th17 Cells/immunology
- Th17 Cells/metabolism
- Time Factors
- Toll-Like Receptor 4/drug effects
- Toll-Like Receptor 4/metabolism
- Trinitrobenzenesulfonic Acid
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Affiliation(s)
- Geum-Dan Kang
- Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, 1, Hoegi, Dongdaemun-gu, Seoul 130-701, South Korea
| | - Dong-Hyun Kim
- Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, 1, Hoegi, Dongdaemun-gu, Seoul 130-701, South Korea.
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35
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The mouse gut microbiome revisited: From complex diversity to model ecosystems. Int J Med Microbiol 2016; 306:316-327. [DOI: 10.1016/j.ijmm.2016.03.002] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2016] [Revised: 03/01/2016] [Accepted: 03/02/2016] [Indexed: 02/06/2023] Open
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36
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Liu YW, Ong WK, Su YW, Hsu CC, Cheng TH, Tsai YC. Anti-inflammatory effects of Lactobacillus brevis K65 on RAW 264.7 cells and in mice with dextran sulphate sodium-induced ulcerative colitis. Benef Microbes 2016; 7:387-96. [PMID: 26925602 DOI: 10.3920/bm2015.0109] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Lactic acid bacteria (LAB) with anti-inflammatory effects may be beneficial to the prevention or treatment for inflammation-related diseases, such as inflammatory bowel diseases. In an in vitro assay, heat-killed Lactobacillus brevis K65 (K65) reduced lipopolysaccharide-induced production of nitric oxide, tumour necrosis factor (TNF)-α and prostaglandin E2 in RAW 264.7 cells. In RAW 264.7 cells stably expressing an ind=ucible nitric oxide synthase (iNOS) reporter, viable K65 showed greater inhibition of iNOS production than its heat-killed form. In order to further examine the in vivo anti-inflammatory effect of K65, viable K65 was orally administered to BALB/c mice before and during the period of dextran sulphate sodium (DSS)-induced ulcerative colitis (UC). K65 improved UC symptoms, including reduced the levels of the pro-inflammatory cytokines, TNF-α, interleukin (IL)-6 and IL-1β, and lowered the activity of myeloperoxidase. Furthermore, K65 inhibited TNF-α, cyclo-oxygenase 2, forkhead box P3, and Toll-like receptor 4 mRNA expression in the colonic tissue of DSS-induced UC mice. Taken together, K65, a LAB with in vitro anti-inflammatory activity showed preventive effects on mice with DSS-induced UC by lowering the expression of inflammatory molecules.
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Affiliation(s)
- Y-W Liu
- 1 Institute of Biochemistry and Molecular Biology, National Yang-Ming University, No. 155, Sec. 2, Linong Street, 11221 Taipei City, Taiwan, ROC
| | - W-K Ong
- 1 Institute of Biochemistry and Molecular Biology, National Yang-Ming University, No. 155, Sec. 2, Linong Street, 11221 Taipei City, Taiwan, ROC
| | - Y-W Su
- 1 Institute of Biochemistry and Molecular Biology, National Yang-Ming University, No. 155, Sec. 2, Linong Street, 11221 Taipei City, Taiwan, ROC
| | - C-C Hsu
- 2 Bened Biomedicals Co., Ltd., 2F.-2, No.129, Sec. 2, Zhongshan N. Rd., Zhongshan Dist., 10448 Taipei City, Taiwan, ROC
| | - T-H Cheng
- 1 Institute of Biochemistry and Molecular Biology, National Yang-Ming University, No. 155, Sec. 2, Linong Street, 11221 Taipei City, Taiwan, ROC
| | - Y-C Tsai
- 1 Institute of Biochemistry and Molecular Biology, National Yang-Ming University, No. 155, Sec. 2, Linong Street, 11221 Taipei City, Taiwan, ROC
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37
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Bugging inflammation: role of the gut microbiota. Clin Transl Immunology 2016; 5:e72. [PMID: 27195115 PMCID: PMC4855262 DOI: 10.1038/cti.2016.12] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2016] [Revised: 03/10/2016] [Accepted: 03/10/2016] [Indexed: 12/12/2022] Open
Abstract
The advent of vaccination and improved hygiene have eliminated many of the deadly infectious pathogens in developed nations. However, the incidences of inflammatory diseases, such as inflammatory bowel disease, asthma, obesity and diabetes are increasing dramatically. Research in the recent decades revealed that it is indeed the lack of early childhood microbial exposure, increase use of antibiotics, as well as increase consumption of processed foods high in carbohydrates and fats, and lacking fibre, which wreak havoc on the proper development of immunity and predispose the host to elevated inflammatory conditions. Although largely unexplored and under-appreciated until recent years, these factors impact significantly on the composition of the gut microbiota (a collection of microorganisms that live within the host mucosal tissue) and inadvertently play intricate and pivotal roles in modulating an appropriate host immune response. The suggestion that shifts in the composition of host microbiota is a risk factor for inflammatory disease raises an exciting opportunity whereby the microbiota may also present as a potential modifiable component or therapeutic target for inflammatory diseases. This review provides insights into the interactions between the microbiota and the immune system, how these affect disease phenotypes, and explore current and emerging therapies that target the gut microbiota as potential treatment for inflammatory diseases.
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38
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Murphy K, Mitchell CM. The Interplay of Host Immunity, Environment and the Risk of Bacterial Vaginosis and Associated Reproductive Health Outcomes. J Infect Dis 2016; 214 Suppl 1:S29-35. [PMID: 27056955 DOI: 10.1093/infdis/jiw140] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Bacterial vaginosis (BV) is one of the most common causes of vaginal symptoms in US women, but its causal mechanism has not yet been defined. BV is more prevalent in women who are immunosuppressed, and several risk factors for the development of BV are associated with lower quantities of immune mediators in vaginal fluid. In contrast, the poor reproductive health outcomes associated with BV, such as preterm birth and human immunodeficiency virus type 1 acquisition, are associated with increased levels of proinflammatory immune mediators in the genital tract. In this article, we discuss how variations in the host immune profile and environmental effects on host immunity may influence the risk of BV, as well as the risk of complications associated with BV.
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Affiliation(s)
- Kerry Murphy
- Division of Infectious Diseases, Albert Einstein College of Medicine, Bronx, New York
| | - Caroline M Mitchell
- Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston
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39
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Wei X, Wang S, Zhao X, Wang X, Li H, Lin W, Lu J, Zhurina D, Li B, Riedel CU, Sun Y, Yuan J. Proteomic Profiling of Bifidobacterium bifidum S17 Cultivated Under In Vitro Conditions. Front Microbiol 2016; 7:97. [PMID: 26903976 PMCID: PMC4751264 DOI: 10.3389/fmicb.2016.00097] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2015] [Accepted: 01/18/2016] [Indexed: 01/04/2023] Open
Abstract
Bifidobacteria are frequently used in probiotic food and dairy products. Bifidobacterium bifidum S17 is a promising probiotic candidate strain that displays strong adhesion to intestinal epithelial cells and elicits potent anti-inflammatory capacity both in vitro and in murine models of colitis. The recently sequenced genome of B. bifidum S17 has a size of about 2.2 Mb and encodes 1,782 predicted protein-coding genes. In the present study, a comprehensive proteomic profiling was carried out to identify and characterize proteins expressed by B. bifidum S17. A total of 1148 proteins entries were identified by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), representing 64.4% of the predicted proteome. 719 proteins could be assigned to functional categories according to cluster of orthologous groups of proteins (COGs). The COG distribution of the detected proteins highly correlates with that of the complete predicted proteome suggesting a good coverage and representation of the genomic content of B. bifidum S17 by the proteome. COGs that were highly present in the proteome of B. bifidum S17 were Translation, Amino Acid Transport and Metabolism, and Carbohydrate Transport and Metabolism. Complete sets of enzymes for both the bifidus shunt and the Embden-Meyerh of pathway were identified. Further bioinformatic analysis yielded 28 proteins with a predicted extracellular localization including 14 proteins with an LPxTG-motif for cell wall anchoring and two proteins (elongation factor Tu and enolase) with a potential moonlighting function in adhesion. Amongst the predicted extracellular proteins were five of six pilin proteins encoded in the B. bifidum S17 genome as well as several other proteins with a potential role in interaction with host structures. The presented results are the first compilation of a proteomic reference profile for a B. bifidum strain and will facilitate analysis of the molecular mechanisms of physiology, host-interactions and beneficial effects of a potential probiotic strain.
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Affiliation(s)
- Xiao Wei
- Institute of Disease Control and Prevention, Academy of Military Medical Sciences Beijing, China
| | - Simiao Wang
- Institute of Disease Control and Prevention, Academy of Military Medical Sciences Beijing, China
| | - Xiangna Zhao
- Institute of Disease Control and Prevention, Academy of Military Medical Sciences Beijing, China
| | - Xuesong Wang
- Institute of Disease Control and Prevention, Academy of Military Medical Sciences Beijing, China
| | - Huan Li
- Institute of Disease Control and Prevention, Academy of Military Medical Sciences Beijing, China
| | - Weishi Lin
- Institute of Disease Control and Prevention, Academy of Military Medical Sciences Beijing, China
| | - Jing Lu
- Institute of Disease Control and Prevention, Academy of Military Medical Sciences Beijing, China
| | - Daria Zhurina
- Institute of Microbiology and Biotechnology, University of Ulm Ulm, Germany
| | - Boxing Li
- Institute of Disease Control and Prevention, Academy of Military Medical Sciences Beijing, China
| | - Christian U Riedel
- Institute of Microbiology and Biotechnology, University of Ulm Ulm, Germany
| | - Yansong Sun
- Institute of Disease Control and Prevention, Academy of Military Medical Sciences Beijing, China
| | - Jing Yuan
- Institute of Disease Control and Prevention, Academy of Military Medical Sciences Beijing, China
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