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Pérez Escriva P, Correia Tavares Bernardino C, Letellier E. De-coding the complex role of microbial metabolites in cancer. Cell Rep 2025; 44:115358. [PMID: 40023841 DOI: 10.1016/j.celrep.2025.115358] [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: 08/09/2024] [Revised: 12/11/2024] [Accepted: 02/06/2025] [Indexed: 03/04/2025] Open
Abstract
The human microbiome, an intricate ecosystem of trillions of microbes residing across various body sites, significantly influences cancer, a leading cause of morbidity and mortality worldwide. Recent studies have illuminated the microbiome's pivotal role in cancer development, either through direct cellular interactions or by secreting bioactive compounds such as metabolites. Microbial metabolites contribute to cancer initiation through mechanisms such as DNA damage, epithelial barrier dysfunction, and chronic inflammation. Furthermore, microbial metabolites exert dual roles on cancer progression and response to therapy by modulating cellular metabolism, gene expression, and signaling pathways. Understanding these complex interactions is vital for devising new therapeutic strategies. This review highlights microbial metabolites as promising targets for cancer prevention and treatment, emphasizing their impact on therapy responses and underscoring the need for further research into their roles in metastasis and therapy resistance.
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Affiliation(s)
- Pau Pérez Escriva
- Department of Life Sciences and Medicine, Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Catarina Correia Tavares Bernardino
- Department of Life Sciences and Medicine, Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Elisabeth Letellier
- Department of Life Sciences and Medicine, Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.
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Gawey BJ, Mars RA, Kashyap PC. The role of the gut microbiome in disorders of gut-brain interaction. FEBS J 2025; 292:1357-1377. [PMID: 38922780 PMCID: PMC11664017 DOI: 10.1111/febs.17200] [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: 01/14/2024] [Revised: 04/03/2024] [Accepted: 06/05/2024] [Indexed: 06/28/2024]
Abstract
Disorders of Gut-Brain Interaction (DGBI) are widely prevalent and commonly encountered in gastroenterology practice. While several peripheral and central mechanisms have been implicated in the pathogenesis of DGBI, a recent body of work suggests an important role for the gut microbiome. In this review, we highlight how gut microbiota and their metabolites affect physiologic changes underlying symptoms in DGBI, with a particular focus on their mechanistic influence on GI transit, visceral sensitivity, intestinal barrier function and secretion, and CNS processing. This review emphasizes the complexity of local and distant effects of microbial metabolites on physiological function, influenced by factors such as metabolite concentration, duration of metabolite exposure, receptor location, host genetics, and underlying disease state. Large-scale in vitro work has elucidated interactions between host receptors and the microbial metabolome but there is a need for future research to integrate such preclinical findings with clinical studies. The development of novel, targeted therapeutic strategies for DGBI hinges on a deeper understanding of these metabolite-host interactions, offering exciting possibilities for the future of treatment of DGBI.
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Affiliation(s)
- Brent J Gawey
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Ruben A Mars
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Purna C Kashyap
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
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Xie C, Qi C, Zhang J, Wang W, Meng X, Aikepaer A, Lin Y, Su C, Liu Y, Feng X, Gao H. When short-chain fatty acids meet type 2 diabetes mellitus: Revealing mechanisms, envisioning therapies. Biochem Pharmacol 2025; 233:116791. [PMID: 39894305 DOI: 10.1016/j.bcp.2025.116791] [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: 10/25/2024] [Revised: 01/19/2025] [Accepted: 01/30/2025] [Indexed: 02/04/2025]
Abstract
Evidence is accumulating that short-chain fatty acids (SCFAs) produced by the gut microbiota play pivotal roles in host metabolism. They contribute to the metabolic regulation and energy homeostasis of the host not only by preserving intestinal health and serving as energy substrates but also by entering the systemic circulation as signaling molecules, affecting the gut-brain axis and neuroendocrine-immune network. This review critically summarizes the current knowledge regarding the effects of SCFAs in the fine-tuning of the pathogenesis of type 2 diabetes mellitus (T2DM) and insulin resistance, with an emphasis on the complex relationships among diet, microbiota-derived metabolites, T2DM inflammation, glucose metabolism, and the underlying mechanisms involved. We hold an optimistic view that elucidating how diet can influence gut bacterial composition and activity, SCFA production, and metabolic functions in the host will advance our understanding of the mutual interactions of the intestinal microbiota with other metabolically active organs, and may pave the way for harnessing these pathways to develop novel personalized therapeutics for glucometabolic disorders.
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Affiliation(s)
- Cong Xie
- Department of Endocrinology, Yuquan Hospital, School of Clinical Medicine, Tsinghua University, Beijing 100040 China
| | - Cong Qi
- Department of Endocrinology, Yuquan Hospital, School of Clinical Medicine, Tsinghua University, Beijing 100040 China
| | - Jianwen Zhang
- Department of Endocrinology, Yuquan Hospital, School of Clinical Medicine, Tsinghua University, Beijing 100040 China; School of Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617 China
| | - Wei Wang
- Department of Endocrinology, Yuquan Hospital, School of Clinical Medicine, Tsinghua University, Beijing 100040 China
| | - Xing Meng
- Department of Endocrinology, Yuquan Hospital, School of Clinical Medicine, Tsinghua University, Beijing 100040 China; School of Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617 China
| | - Aifeila Aikepaer
- Department of Endocrinology, Yuquan Hospital, School of Clinical Medicine, Tsinghua University, Beijing 100040 China; Dongzhimen Hospital, the First Clinical Medical School of Beijing University of Chinese Medicine, Beijing 100700 China
| | - Yuhan Lin
- Department of Endocrinology, Yuquan Hospital, School of Clinical Medicine, Tsinghua University, Beijing 100040 China; Dongzhimen Hospital, the First Clinical Medical School of Beijing University of Chinese Medicine, Beijing 100700 China
| | - Chang Su
- Life Science and Engineering College, Northwest Minzu University, Lanzhou 730124 China
| | - Yunlu Liu
- Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700 China
| | - Xingzhong Feng
- Department of Endocrinology, Yuquan Hospital, School of Clinical Medicine, Tsinghua University, Beijing 100040 China.
| | - Huijuan Gao
- Department of Endocrinology, Yuquan Hospital, School of Clinical Medicine, Tsinghua University, Beijing 100040 China.
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Zhou Y, Ding Y, Li Y, Sheng Q, Han C, Fan Y, Wang Z, Lu B, Dou X, Zhang C. Sodium Butyrate Inhibits Necroptosis by Regulating MLKL via E2F1 in Intestinal Epithelial Cells of Liver Cirrhosis. J Clin Transl Hepatol 2025; 13:105-117. [PMID: 39917471 PMCID: PMC11797820 DOI: 10.14218/jcth.2024.00221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 10/16/2024] [Accepted: 10/28/2024] [Indexed: 02/09/2025] Open
Abstract
Background and Aims Necroptosis is critical for regulating intestinal epithelial cells (IECs). Butyric acid (BA), produced during intestinal microbial metabolism, protects the intestinal epithelial barrier. However, whether necroptosis occurs in IECs during liver cirrhosis and whether sodium butyrate (NaB) can regulate necroptosis have not yet been reported. In this study, we aimed to investigate whether IECs undergo necroptosis in cirrhosis and whether NaB can regulate necroptosis and the related regulatory mechanisms. Methods Serum levels of RIPK3, MLKL, and Zonulin, as well as fecal BA levels, were measured and correlated in 48 patients with liver cirrhosis and 20 healthy controls. A rat model of liver cirrhosis was established, and NaB was administered. The expressions of MLKL, p-MLKL, and tight junction proteins were measured. We conducted an in vitro investigation of the effect of NaB on necroptosis in the HT29 cell line. Results Serum levels of RIPK3, MLKL, and Zonulin in the liver cirrhosis group were higher, while fecal BA levels were lower than those in the control group. Zonulin levels were positively correlated with RIPK3 and MLKL levels, while fecal BA levels were negatively correlated with serum MLKL levels, but not with RIPK3 levels. NaB reduced the mRNA and protein expression of MLKL but had no effect on RIPK1 and RIPK3 in vitro. Rescue experiments demonstrated that NaB inhibited necroptosis through E2F1-mediated regulation of MLKL. Conclusions NaB alleviates intestinal mucosal injury and reduces necroptosis in IECs in liver cirrhosis. It also inhibits the necroptosis of IECs and protects the intestinal barrier by reducing E2F1 expression and downregulating MLKL expression levels. These results can be employed to develop a novel strategy for treating complications arising from liver cirrhosis.
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Affiliation(s)
- Yimeng Zhou
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
- Key Laboratory of Viral Hepatitis, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Yang Ding
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
- Key Laboratory of Viral Hepatitis, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Yanwei Li
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Qiuju Sheng
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Chao Han
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Yaoxin Fan
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
- Key Laboratory of Viral Hepatitis, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Ziyi Wang
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Bingchao Lu
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Xiaoguang Dou
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
- Key Laboratory of Viral Hepatitis, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Chong Zhang
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
- Key Laboratory of Viral Hepatitis, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
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Li B, Zhang X, Zhang Q, Zheng T, Li Q, Yang S, Shao J, Guan W, Zhang S. Nutritional strategies to reduce intestinal cell apoptosis by alleviating oxidative stress. Nutr Rev 2025; 83:e518-e532. [PMID: 38626282 DOI: 10.1093/nutrit/nuae023] [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] [Indexed: 04/18/2024] Open
Abstract
The gut barrier is the first line of defense against harmful substances and pathogens in the intestinal tract. The balance of proliferation and apoptosis of intestinal epithelial cells (IECs) is crucial for maintaining the integrity of the intestinal mucosa and its function. However, oxidative stress and inflammation can cause DNA damage and abnormal apoptosis of the IECs, leading to the disruption of the intestinal epithelial barrier. This, in turn, can directly or indirectly cause various acute and chronic intestinal diseases. In recent years, there has been a growing understanding of the vital role of dietary ingredients in gut health. Studies have shown that certain amino acids, fibers, vitamins, and polyphenols in the diet can protect IECs from excessive apoptosis caused by oxidative stress, and limit intestinal inflammation. This review aims to describe the molecular mechanism of apoptosis and its relationship with intestinal function, and to discuss the modulation of IECs' physiological function, the intestinal epithelial barrier, and gut health by various nutrients. The findings of this review may provide a theoretical basis for the use of nutritional interventions in clinical intestinal disease research and animal production, ultimately leading to improved human and animal intestinal health.
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Affiliation(s)
- Baofeng Li
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Xiaoli Zhang
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Qianzi Zhang
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Tenghui Zheng
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Qihui Li
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Siwang Yang
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Jiayuan Shao
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Wutai Guan
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Shihai Zhang
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, China
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Sardaro MLS, Grote V, Baik J, Atallah M, Amato KR, Ring M. Effects of Vegetable and Fruit Juicing on Gut and Oral Microbiome Composition. Nutrients 2025; 17:458. [PMID: 39940316 PMCID: PMC11820471 DOI: 10.3390/nu17030458] [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: 12/23/2024] [Revised: 01/23/2025] [Accepted: 01/23/2025] [Indexed: 02/14/2025] Open
Abstract
BACKGROUND In recent years, juicing has often been promoted as a convenient way to increase fruit and vegetable intake, with juice-only diets marketed for digestive cleansing and overall health improvement. However, juicing removes most insoluble fiber, which may diminish the health benefits of whole fruits and vegetables. Lower fiber intake can alter the microbiota, affecting metabolism, immunity, and mental health, though little is known about juicing's specific effects on the microbiota. This study addresses this gap by exploring how juicing impacts gut and oral microbiome composition in an intervention study. METHODS Fourteen participants followed one of three diets-exclusive juice, juice plus food, or plant-based food-for three days. Microbiota samples (stool, saliva, and inner cheek swabs) were collected at baseline, after a pre-intervention elimination diet, immediately after juice intervention, and 14 days after intervention. Moreover, 16S rRNA gene amplicon sequencing was used to analyze microbiota taxonomic composition. RESULTS The saliva microbiome differed significantly in response to the elimination diet (unweighted UniFrac: F = 1.72, R = 0.06, p < 0.005; weighted UniFrac: F = 7.62, R = 0.23, p-value = 0.0025) with a significant reduction in Firmicutes (p = 0.004) and a significant increase in Proteobacteria (p = 0.005). The juice intervention diets were also associated with changes in the saliva and cheek microbiota, particularly in the relative abundances of pro-inflammatory bacterial families, potentially due to the high sugar and low fiber intake of the juice-related products. Although no significant shifts in overall gut microbiota composition were observed, with either the elimination diet or the juice intervention diets, bacterial taxa associated with gut permeability, inflammation, and cognitive decline increased in relative abundance. CONCLUSIONS These findings suggest that short-term juice consumption may negatively affect the microbiota.
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Affiliation(s)
- Maria Luisa Savo Sardaro
- Department of Anthropology, Northwestern University, Evanston, IL 60208, USA; (J.B.); (K.R.A.)
- Department for the Promotion of Human Sciences and Quality of Life, San Raffaele University, 00166 Rome, Italy
| | - Veronika Grote
- Osher Center for Integrative Health, Northwestern University, Chicago, IL 60611, USA;
| | - Jennifer Baik
- Department of Anthropology, Northwestern University, Evanston, IL 60208, USA; (J.B.); (K.R.A.)
| | - Marco Atallah
- Department of Food Science and Human Nutrition, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA;
| | - Katherine Ryan Amato
- Department of Anthropology, Northwestern University, Evanston, IL 60208, USA; (J.B.); (K.R.A.)
| | - Melinda Ring
- Osher Center for Integrative Health, Northwestern University, Chicago, IL 60611, USA;
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Termite F, Archilei S, D’Ambrosio F, Petrucci L, Viceconti N, Iaccarino R, Liguori A, Gasbarrini A, Miele L. Gut Microbiota at the Crossroad of Hepatic Oxidative Stress and MASLD. Antioxidants (Basel) 2025; 14:56. [PMID: 39857390 PMCID: PMC11759774 DOI: 10.3390/antiox14010056] [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: 12/13/2024] [Revised: 12/30/2024] [Accepted: 01/02/2025] [Indexed: 01/27/2025] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver condition marked by excessive lipid accumulation in hepatic tissue. This disorder can lead to a range of pathological outcomes, including metabolic dysfunction-associated steatohepatitis (MASH) and cirrhosis. Despite extensive research, the molecular mechanisms driving MASLD initiation and progression remain incompletely understood. Oxidative stress and lipid peroxidation are pivotal in the "multiple parallel hit model", contributing to hepatic cell death and tissue damage. Gut microbiota plays a substantial role in modulating hepatic oxidative stress through multiple pathways: impairing the intestinal barrier, which results in bacterial translocation and chronic hepatic inflammation; modifying bile acid structure, which impacts signaling cascades involved in lipidic metabolism; influencing hepatocytes' ferroptosis, a form of programmed cell death; regulating trimethylamine N-oxide (TMAO) metabolism; and activating platelet function, both recently identified as pathogenetic factors in MASH progression. Moreover, various exogenous factors impact gut microbiota and its involvement in MASLD-related oxidative stress, such as air pollution, physical activity, cigarette smoke, alcohol, and dietary patterns. This manuscript aims to provide a state-of-the-art overview focused on the intricate interplay between gut microbiota, lipid peroxidation, and MASLD pathogenesis, offering insights into potential strategies to prevent disease progression and its associated complications.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Luca Miele
- CEMAD Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy (S.A.)
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Wang XW, Ding YL, Li CL, Ma Q, Shi YG, Liu GE, Li CJ, Kang XL. Effects of rumen metabolite butyric acid on bovine skeletal muscle satellite cells proliferation, apoptosis and transcriptional states during myogenic differentiation. Domest Anim Endocrinol 2025; 90:106892. [PMID: 39418766 DOI: 10.1016/j.domaniend.2024.106892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 10/09/2024] [Accepted: 10/10/2024] [Indexed: 10/19/2024]
Abstract
Butyric acid, a pivotal short-chain fatty acid in rumen digestion, profoundly influences animal digestive and locomotor systems. Extensive research indicates its direct or indirect involvement in the growth and development of muscle and fat cells. However, the impact of butyric acid on the proliferation and differentiation of bovine skeletal muscle satellite cells (SMSCs) remains unclear. This study aimed to elucidate the effects of butyrate on SMSCs proliferation and differentiation. After isolating, SMSCs were subjected to varying concentrations of sodium butyrate (NaB) during the proliferation and differentiation stages. Optimal treatment conditions (1 mM NaB for 2 days) were determined based on proliferative force, cell viability, and mRNA expression of proliferation and differentiation marker genes. Transcriptome sequencing was employed to screen for differential gene expression between 1 mM NaB-treated and untreated groups during SMSCs differentiation. Results indicated that lower NaB concentrations (≤1.0 mM) inhibited proliferation while promoting differentiation and apoptosis after a 2-day treatment. Conversely, higher NaB concentrations (≥2.0 mM) suppressed proliferation and differentiation and induced apoptosis. Transcriptome sequencing revealed differential expression of genes(ND1, ND3, CYTB, COX2, ATP6, MYOZ2, MYOZ3, MYBPC1 and ATP6V0A4,etc.) were associated with SMSCs differentiation and energy metabolism, enriching pathways such as Oxidative phosphorylation, MAPK, and Wnt signaling. These findings offer valuable insights into the molecular mechanisms underlying butyrate regulation of bovine SMSCs proliferation and differentiation, as well as muscle fiber type conversion in the future study.
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Affiliation(s)
- Xiao-Wei Wang
- Key Laboratory of Ruminant Molecular and Cellular Breeding, College of Animal Science and Technology, Ningxia University, Yinchuan 750021, China; Institute of Animal Science, Ningxia Academy of Agriculture and Forestry Sciences, Yinchuan750002, China
| | - Yan-Ling Ding
- Key Laboratory of Ruminant Molecular and Cellular Breeding, College of Animal Science and Technology, Ningxia University, Yinchuan 750021, China
| | - Cheng-Long Li
- Key Laboratory of Ruminant Molecular and Cellular Breeding, College of Animal Science and Technology, Ningxia University, Yinchuan 750021, China
| | - Qing Ma
- Institute of Animal Science, Ningxia Academy of Agriculture and Forestry Sciences, Yinchuan750002, China
| | - Yuan-Gang Shi
- Key Laboratory of Ruminant Molecular and Cellular Breeding, College of Animal Science and Technology, Ningxia University, Yinchuan 750021, China
| | - George E Liu
- Animal Genomics and Improvement Laboratory, Henry A. Wallace Beltsville Agricultural Research Center, Agricultural Research Service, USDA, Beltsville, MD 20705, United States
| | - Cong-Jun Li
- Animal Genomics and Improvement Laboratory, Henry A. Wallace Beltsville Agricultural Research Center, Agricultural Research Service, USDA, Beltsville, MD 20705, United States.
| | - Xiao-Long Kang
- Key Laboratory of Ruminant Molecular and Cellular Breeding, College of Animal Science and Technology, Ningxia University, Yinchuan 750021, China.
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Miao S, Li J, Chen Y, Zhao W, Xu M, Liu F, Zou X, Dong X. Targeting gut microbiota and metabolism profiles with coated sodium butyrate to ameliorate high-energy and low-protein diet-induced intestinal barrier dysfunction in laying hens. ANIMAL NUTRITION (ZHONGGUO XU MU SHOU YI XUE HUI) 2024; 19:104-116. [PMID: 39635416 PMCID: PMC11615920 DOI: 10.1016/j.aninu.2024.06.006] [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: 03/30/2024] [Revised: 05/30/2024] [Accepted: 06/11/2024] [Indexed: 12/07/2024]
Abstract
High energy diets are a risk factor for intestinal barrier damage. Butyrate, a major energy source for intestinal epithelial cells, has been shown to improve barrier dysfunction and modulate the gut microbiota. In this trial, we examined the preventative effect of coated sodium butyrate (CSB) on high-energy and low-protein (HELP)-induced intestinal barrier injury in laying hens, and also worked to determine the underlying mechanisms by an integrative analysis of gut microbiota and the metabolome. A total of 216 healthy 28-week-old Huafeng laying hens were randomly assigned to 3 groups with 6 replicates each: the CON group (normal diet), HELP group (HELP diet) and CH500 group (500 mg/kg CSB added to HELP diet). The duration of the trial encompassed a period of 10 weeks. The results revealed that CSB treatment improved the laying rate and mitigated the detrimental effects on intestinal barrier function and the inflammatory response induced by the HELP diet in laying hens (P < 0.05). Microbial profiling analysis revealed that the CSB treatment reshaped the HELP-perturbed gut microbiota and promoted the growth of beneficial bacteria (P < 0.05). Untargeted metabolomics analysis revealed that CSB reduced the metabolites associated with intestinal inflammation (P < 0.05). In conclusion, CSB did not merely modulate alterations in the gut microbiota composition and microbial metabolites but also yielded increased egg production, while mitigating intestinal barrier dysfunction and inflammatory responses induced by HELP in laying hens.
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Affiliation(s)
- Sasa Miao
- Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture and Rural Affairs, The Key Laboratory of Molecular Animal Nutrition, Ministry of Education, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China
| | - Jiankui Li
- Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture and Rural Affairs, The Key Laboratory of Molecular Animal Nutrition, Ministry of Education, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China
| | - Ying Chen
- Hangzhou Zhejiang University Animal Hospital Co., Ltd., Hangzhou 310058, China
| | - Wenyan Zhao
- Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture and Rural Affairs, The Key Laboratory of Molecular Animal Nutrition, Ministry of Education, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China
| | - Mengru Xu
- Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture and Rural Affairs, The Key Laboratory of Molecular Animal Nutrition, Ministry of Education, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China
| | - Fang Liu
- Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture and Rural Affairs, The Key Laboratory of Molecular Animal Nutrition, Ministry of Education, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China
| | - Xiaoting Zou
- Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture and Rural Affairs, The Key Laboratory of Molecular Animal Nutrition, Ministry of Education, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China
| | - Xinyang Dong
- Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture and Rural Affairs, The Key Laboratory of Molecular Animal Nutrition, Ministry of Education, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China
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10
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Yin T, Zhang X, Xiong Y, Li B, Guo D, Sha Z, Lin X, Wu H. Exploring gut microbial metabolites as key players in inhibition of cancer progression: Mechanisms and therapeutic implications. Microbiol Res 2024; 288:127871. [PMID: 39137590 DOI: 10.1016/j.micres.2024.127871] [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: 05/16/2024] [Revised: 07/19/2024] [Accepted: 08/06/2024] [Indexed: 08/15/2024]
Abstract
The gut microbiota plays a critical role in numerous biochemical processes essential for human health, such as metabolic regulation and immune system modulation. An increasing number of research suggests a strong association between the gut microbiota and carcinogenesis. The diverse metabolites produced by gut microbiota can modulate cellular gene expression, cell cycle dynamics, apoptosis, and immune system functions, thereby exerting a profound influence on cancer development and progression. A healthy gut microbiota promotes substance metabolism, stimulates immune responses, and thereby maintains the long-term homeostasis of the intestinal microenvironment. When the gut microbiota becomes imbalanced and disrupts the homeostasis of the intestinal microenvironment, the risk of various diseases increases. This review aims to elucidate the impact of gut microbial metabolites on cancer initiation and progression, focusing on short-chain fatty acids (SCFAs), polyamines (PAs), hydrogen sulfide (H2S), secondary bile acids (SBAs), and microbial tryptophan catabolites (MTCs). By detailing the roles and molecular mechanisms of these metabolites in cancer pathogenesis and therapy, this article sheds light on dual effects on the host at different concentrations of metabolites and offers new insights into cancer research.
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Affiliation(s)
- Tianxiang Yin
- School of Life Sciences, Chongqing University, Chongqing 401331, China
| | - Xiang Zhang
- Medical School, Yan'an University, Yan'an 716000, China
| | - Yan Xiong
- School of Life Sciences, Chongqing University, Chongqing 401331, China
| | - Bohao Li
- School of Life Sciences, Chongqing University, Chongqing 401331, China
| | - Dong Guo
- School of Life Sciences, Chongqing University, Chongqing 401331, China
| | - Zhou Sha
- School of Life Sciences, Chongqing University, Chongqing 401331, China
| | - Xiaoyuan Lin
- Department of Clinical Microbiology and Immunology, College of Pharmacy and Medical Laboratory, Army Medical University (Third Military Medical University), Chongqing 400038, China.
| | - Haibo Wu
- School of Life Sciences, Chongqing University, Chongqing 401331, China.
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Donald K, Finlay BB. Experimental models of antibiotic exposure and atopic disease. FRONTIERS IN ALLERGY 2024; 5:1455438. [PMID: 39525399 PMCID: PMC11543581 DOI: 10.3389/falgy.2024.1455438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Accepted: 10/07/2024] [Indexed: 11/16/2024] Open
Abstract
In addition to numerous clinical studies, research using experimental models have contributed extensive evidence to the link between antibiotic exposure and atopic disease. A number of mouse models of allergy have been developed and used to uncover the specific effects of various microbiota members and perturbations on allergy development. Studies in mice that lack microbes entirely have also demonstrated the various components of the immune system that require microbial exposure. The importance of the early-life period and the mechanisms by which atopy "protective" species identified in human cohorts promote immune development have been elucidated in mice. Finally, non-animal models involving human-derived cells shed light on specific effects of bacteria on human epithelial and immune responses. When considered alongside clinical cohort studies, experimental model systems have provided crucial evidence for the link between the neonatal gut microbiota and allergic disease, immensely supporting the stewardship of antibiotic administration in infants. The following review aims to describe the range of experimental models used for studying factors that affect the relationship between the gut microbiota and allergic disease and summarize key findings that have come from research in animal and in vitro models.
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Affiliation(s)
- Katherine Donald
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
| | - B. Brett Finlay
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
- Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada
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12
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Zhao J, Lei Y, Zhang X, Li Z. A bibliometric analysis of global research on short chain fatty acids in neurological diseases. Medicine (Baltimore) 2024; 103:e40102. [PMID: 39465784 PMCID: PMC11479477 DOI: 10.1097/md.0000000000040102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Accepted: 09/26/2024] [Indexed: 10/29/2024] Open
Abstract
BACKGROUND The interest on short chain fatty acids (SCFAs) regulating the progress of neurological diseases has gained significant attention in recent years. This bibliometric analysis aimed to provide insights into the current state and future trends of global research on SCFAs in neurological research. METHODS To analysis the general trend of publications, the scientific output in this field from 1995 to 2024 was first retrieved from the Web of Science Core Collection, Scopus, and PubMed with SCFAs-related and neurological diseases related terms as the subjects. Based on above publication analysis, rapid development stage was marked as 2016 to 2024 and 878 relevant original articles in rapid development stage was retrieved with the time limit from 2016 to 2024. Key bibliometric indicators were calculated and evaluated using CiteSpace with these 878 articles. RESULTS SCFAs are related to the occurrence and development of neurological diseases. China and the USA have contributed in a significant way to foster a better understanding on SCFAs in neurological diseases. The hot theme of research have gradually shifted from neurodegenerative diseases to psychical diseases. In the aspect of mechanism research, the current hotspot is inflammation. SCFAs are able to modulate oxidative stress and microglia maturation, morphology and function to intervene in the development of neurological diseases and thus SCFAs interventions are promising to treat neurological diseases. 2016 to 2024 is the fast-developing stage in this field. In this stage the publications dramatically increased and were of high quality. CONCLUSION SCFAs in neurological research will continue to be an active area in the near future. Future trends might be correlation analysis and neurotherapeutics of SCFAs on patients with psychical diseases and deeper mechanism research is still needed.
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Affiliation(s)
- Jiuhong Zhao
- Institute of Wound Prevention and Treatment, Shanghai University of Medicine and Health Sciences, Shanghai, China
- Department of Human Anatomy and Histology, School of Fundamental Medicine, Shanghai University of Medicine and Health Sciences, Shanghai, China
| | - Yihan Lei
- Institute of Wound Prevention and Treatment, Shanghai University of Medicine and Health Sciences, Shanghai, China
| | - Xinyuan Zhang
- Department of Forensic Clinical Medicine, School of Forensic Medicine, China Medical University, Shenyang, China
| | - Zhihong Li
- Institute of Wound Prevention and Treatment, Shanghai University of Medicine and Health Sciences, Shanghai, China
- Department of Human Anatomy and Histology, School of Fundamental Medicine, Shanghai University of Medicine and Health Sciences, Shanghai, China
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13
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Feng Y, Pan M, Li R, He W, Chen Y, Xu S, Chen H, Xu H, Lin Y. Recent developments and new directions in the use of natural products for the treatment of inflammatory bowel disease. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 132:155812. [PMID: 38905845 DOI: 10.1016/j.phymed.2024.155812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Revised: 05/13/2024] [Accepted: 06/06/2024] [Indexed: 06/23/2024]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) represents a significant global health challenge, and there is an urgent need to explore novel therapeutic interventions. Natural products have demonstrated highly promising effectiveness in the treatment of IBD. PURPOSE This study systematically reviews the latest research advancements in leveraging natural products for IBD treatment. METHODS This manuscript strictly adheres to the PRISMA guidelines. Relevant literature on the effects of natural products on IBD was retrieved from the PubMed, Web of Science and Cochrane Library databases using the search terms "natural product," "inflammatory bowel disease," "colitis," "metagenomics", "target identification", "drug delivery systems", "polyphenols," "alkaloids," "terpenoids," and so on. The retrieved data were then systematically summarized and reviewed. RESULTS This review assessed the different effects of various natural products, such as polyphenols, alkaloids, terpenoids, quinones, and others, in the treatment of IBD. While these natural products offer promising avenues for IBD management, they also face challenges in terms of clinical translation and drug discovery. The advent of metagenomics, single-cell sequencing, target identification techniques, drug delivery systems, and other cutting-edge technologies heralds a new era in overcoming these challenges. CONCLUSION This paper provides an overview of current research progress in utilizing natural products for the treatment of IBD, exploring how contemporary technological innovations can aid in discovering and harnessing bioactive natural products for the treatment of IBD.
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Affiliation(s)
- Yaqian Feng
- Fujian-Macao Science and Technology Cooperation Base of Traditional Chinese Medicine-Oriented Chronic Disease Prevention and Treatment, Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China
| | - Mengting Pan
- Institute of Structural Pharmacology & TCM Chemical Biology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China
| | - Ruiqiong Li
- College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China
| | - Weishen He
- Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA
| | - Yangyang Chen
- Institute of Structural Pharmacology & TCM Chemical Biology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China
| | - Shaohua Xu
- Institute of Structural Pharmacology & TCM Chemical Biology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China.
| | - Hui Chen
- Department of Gastroenterology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350004, China.
| | - Huilong Xu
- Institute of Structural Pharmacology & TCM Chemical Biology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China.
| | - Yao Lin
- Fujian-Macao Science and Technology Cooperation Base of Traditional Chinese Medicine-Oriented Chronic Disease Prevention and Treatment, Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China.
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14
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Yang M, Cai C, Yang Z, Wang X, Li G, Li J, Liu J, Zhang Z. Effect of dietary fibre on cognitive function and mental health in children and adolescents: a systematic review and meta-analysis. Food Funct 2024; 15:8618-8628. [PMID: 39135486 DOI: 10.1039/d4fo02221a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/28/2024]
Abstract
Objective: The purpose of this study is to investigate the impact of dietary fibre on the mental health and cognitive function of children and adolescents. Methods: All interventional and observational studies that contained information on the relevant population (children and adolescents), intervention/exposures (high dietary fibre consumption) and outcomes (mental and cognitive parameters) were eligible. Eight electronic databases (Embase, Medline, Pubmed, Web of Science, Scopus, PsycINFO, Cochrane Library and ClinicalTrials.gov) were searched up to December 11, 2023. Results: A total of 15 studies (n = 4628) met inclusion criteria, consisting of 9 intervention trials and 6 observational studies. According to observational studies, higher dietary fibre consumption was associated with a 49% reduction in the odds of depression compared to lower intake (P < 0.0001; OR = 0.51; 95% CI: 0.38, 0.69; I2 = 0%). Furthermore, no significant correlations were found between dietary fibre consumption and intelligence or anxiety. Among intervention studies, no significant difference was observed between fibre supplementation and placebo in terms of anxiety (standardized mean difference (SMD): -0.23; 95% CI: -0.72, 0.27), stress (SMD: 0.03; 95% CI: -0.21, 0.28), memory (SMD: 0.46; 95% CI: -0.79, 1.71), or attention (SMD: -2.72; 95% CI: -6.30, 0.86). Conclusion: Evidence from observation studies demonstrated that higher dietary fibre consumption is associated with a decreased odds of depression symptoms, both in childhood and adolescence. However, the causal relationship between dietary fibre intake and mental and cognitive function in children and adolescents still requires further clarification through high-quality intervention studies in the future.
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Affiliation(s)
- Mingyue Yang
- College of Ocean Food and Biological Engineering, Jimei University, Xiamen, Fujian, China.
| | - Chenxi Cai
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, Fujian, China
| | - Zhongmin Yang
- College of Ocean Food and Biological Engineering, Jimei University, Xiamen, Fujian, China.
| | - Xue Wang
- State School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
| | - Guiling Li
- College of Ocean Food and Biological Engineering, Jimei University, Xiamen, Fujian, China.
- Fujian Provincial Engineering Technology Research Center of Marine Functional Food, Xiamen, Fujian, China
| | - Jian Li
- College of Ocean Food and Biological Engineering, Jimei University, Xiamen, Fujian, China.
- Fujian Provincial Engineering Technology Research Center of Marine Functional Food, Xiamen, Fujian, China
| | - Jingwen Liu
- College of Ocean Food and Biological Engineering, Jimei University, Xiamen, Fujian, China.
| | - Zhengxiao Zhang
- College of Ocean Food and Biological Engineering, Jimei University, Xiamen, Fujian, China.
- Fujian Provincial Engineering Technology Research Center of Marine Functional Food, Xiamen, Fujian, China
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15
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Hong L, Ma Z, Jing X, Yang H, Ma J, Pu L, Zhang J. Effects of dietary supplementation of polysaccharide from Agaricus blazei Murr on productive performance, egg quality, blood metabolites, intestinal morphology and microbiota of Korean quail. Anim Biosci 2024; 37:1452-1462. [PMID: 38575122 PMCID: PMC11222865 DOI: 10.5713/ab.23.0441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 12/15/2023] [Accepted: 02/08/2024] [Indexed: 04/06/2024] Open
Abstract
OBJECTIVE This study aimed to investigate the effects of dietary supplementation with Agaricus blazei polysaccharide (ABP) at varying concentrations on the performance, egg quality, blood biochemistry, intestinal morphology, and microflora of quail. METHODS The study involved a total of 2,700 Korean quails, which were randomly divided into three groups. The measured variables encompassed productive performance, egg parameters, carcass parameters, serum metabolites, immune response parameters, antioxidative properties, and gut microbiome. RESULTS The addition of ABP did not have a significant effect on average daily feed intake. However, it was found to increase the average daily egg weight and egg production rate, reduce the feed-egg ratio. There were no significant impacts on egg quality measures such as egg shape index, egg yolk index and color, egg yolk and protein content. However, ABP supplementation significantly increased the Hough unit (p<0.01) and decreased the rate of unqualified eggs (p<0.01). Regarding serum parameters, the inclusion led to an increase in total protein concentration (p<0.05) and a reduction in low-density lipoprotein cholesterol (p<0.05). There were no significant effects observed on immune indicators such as immunoglobulin A (IgA) and IgM. ABP supplementation increased the levels of serum antioxidant indicators, including glutathione peroxidase, total superoxide dismutase (p<0.05), and total antioxidant capacity colorimeter (p<0.05). Furthermore, ABP supplementation significantly elevated the intramuscular fatty acid content in quail meat. Additionally, ABP supplementation demonstrated a significant improvement in the diversity of gut microbiota and induced alterations in the composition of the gut microbiota. CONCLUSION The findings of this study indicate that dietary supplementation of ABP enhanced production performance and antioxidant capacity while increasing the levels of polyunsaturated fatty acids in quail muscle.
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Affiliation(s)
- Liang Hong
- Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Tianjin 300392,
China
- Tianjin Key Laboratory of Green Ecological Feed, Tianjin 301800,
China
| | - Zheng Ma
- Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Tianjin 300392,
China
- College of Animal Science and Technology, Guangxi University, Guangxi 530000,
China
| | - Xueyi Jing
- Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Tianjin 300392,
China
| | - Hua Yang
- Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Tianjin 300392,
China
| | - Jifei Ma
- Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Tianjin 300392,
China
| | - Lei Pu
- Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Tianjin 300392,
China
| | - Jianbin Zhang
- Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Tianjin 300392,
China
- Tianjin Key Laboratory of Green Ecological Feed, Tianjin 301800,
China
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16
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Deyang T, Baig MAI, Dolkar P, Hediyal TA, Rathipriya AG, Bhaskaran M, PandiPerumal SR, Monaghan TM, Mahalakshmi AM, Chidambaram SB. Sleep apnoea, gut dysbiosis and cognitive dysfunction. FEBS J 2024; 291:2519-2544. [PMID: 37712936 DOI: 10.1111/febs.16960] [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: 05/26/2023] [Revised: 08/14/2023] [Accepted: 09/13/2023] [Indexed: 09/16/2023]
Abstract
Sleep disorders are becoming increasingly common, and their distinct effects on physical and mental health require elaborate investigation. Gut dysbiosis (GD) has been reported in sleep-related disorders, but sleep apnoea is of particular significance because of its higher prevalence and chronicity. Cumulative evidence has suggested a link between sleep apnoea and GD. This review highlights the gut-brain communication axis that is mediated via commensal microbes and various microbiota-derived metabolites (e.g. short-chain fatty acids, lipopolysaccharide and trimethyl amine N-oxide), neurotransmitters (e.g. γ-aminobutyric acid, serotonin, glutamate and dopamine), immune cells and inflammatory mediators, as well as the vagus nerve and hypothalamic-pituitary-adrenal axis. This review also discusses the pathological role underpinning GD and altered gut bacterial populations in sleep apnoea and its related comorbid conditions, particularly cognitive dysfunction. In addition, the review examines the preclinical and clinical evidence, which suggests that prebiotics and probiotics may potentially be beneficial in sleep apnoea and its comorbidities through restoration of eubiosis or gut microbial homeostasis that regulates neural, metabolic and immune responses, as well as physiological barrier integrity via the gut-brain axis.
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Affiliation(s)
- Tenzin Deyang
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru, India
| | - Md Awaise Iqbal Baig
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru, India
| | - Phurbu Dolkar
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru, India
| | - Tousif Ahmed Hediyal
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru, India
- Centre for Experimental Pharmacology and Toxicology, Central Animal Facility, JSS Academy of Higher Education & Research, Mysuru, India
| | | | - Mahendran Bhaskaran
- College of Pharmacy and Pharmaceutical Sciences, Frederic and Mary Wolf Center, University of Toledo Health Science Campus, OH, USA
| | - Seithikuruppu R PandiPerumal
- Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India
- Division of Research and Development, Lovely Professional University, Phagwara, India
| | - Tanya M Monaghan
- National Institute for Health Research Nottingham Biomedical Research Centre, University of Nottingham, UK
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, UK
| | - Arehally M Mahalakshmi
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru, India
- Centre for Experimental Pharmacology and Toxicology, Central Animal Facility, JSS Academy of Higher Education & Research, Mysuru, India
- SIG-Brain, Behaviour and Cognitive Neurosciences Research (BBRC), JSS Academy of Higher Education & Research, Mysuru, India
| | - Saravana Babu Chidambaram
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru, India
- Centre for Experimental Pharmacology and Toxicology, Central Animal Facility, JSS Academy of Higher Education & Research, Mysuru, India
- SIG-Brain, Behaviour and Cognitive Neurosciences Research (BBRC), JSS Academy of Higher Education & Research, Mysuru, India
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17
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Yang J, Qin K, Wang Q, Yang X. Deciphering the nutritional strategies for polysaccharides effects on intestinal barrier in broilers: Selectively promote microbial ecosystems. Int J Biol Macromol 2024; 264:130677. [PMID: 38458298 DOI: 10.1016/j.ijbiomac.2024.130677] [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: 09/07/2023] [Revised: 03/03/2024] [Accepted: 03/05/2024] [Indexed: 03/10/2024]
Abstract
The gut microbiota, a complex and dynamic microbial ecosystem, plays a crucial role in regulating the intestinal barrier. Polysaccharide foraging is specifically dedicated to establishing and maintaining microbial communities, contributing to the shaping of the intestinal ecosystem and ultimately enhancing the integrity of the intestinal barrier. The utilization and regulation of individual polysaccharides often rely on distinct gut-colonizing bacteria. The products of their metabolism not only benefit the formation of the ecosystem but also facilitate cross-feeding partnerships. In this review, we elucidate the mechanisms by which specific bacteria degrade polysaccharides, and how polysaccharide metabolism shapes the microbial ecosystem through cross-feeding. Furthermore, we explore how selectively promoting microbial ecosystems and their metabolites contributes to improvements in the integrity of the intestinal barrier.
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Affiliation(s)
- Jiantao Yang
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
| | - Kailong Qin
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
| | - Qianggang Wang
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
| | - Xiaojun Yang
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
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18
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Aburto MR, Cryan JF. Gastrointestinal and brain barriers: unlocking gates of communication across the microbiota-gut-brain axis. Nat Rev Gastroenterol Hepatol 2024; 21:222-247. [PMID: 38355758 DOI: 10.1038/s41575-023-00890-0] [Citation(s) in RCA: 64] [Impact Index Per Article: 64.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/20/2023] [Indexed: 02/16/2024]
Abstract
Crosstalk between gut and brain has long been appreciated in health and disease, and the gut microbiota is a key player in communication between these two distant organs. Yet, the mechanisms through which the microbiota influences development and function of the gut-brain axis remain largely unknown. Barriers present in the gut and brain are specialized cellular interfaces that maintain strict homeostasis of different compartments across this axis. These barriers include the gut epithelial barrier, the blood-brain barrier and the blood-cerebrospinal fluid barrier. Barriers are ideally positioned to receive and communicate gut microbial signals constituting a gateway for gut-microbiota-brain communication. In this Review, we focus on how modulation of these barriers by the gut microbiota can constitute an important channel of communication across the gut-brain axis. Moreover, barrier malfunction upon alterations in gut microbial composition could form the basis of various conditions, including often comorbid neurological and gastrointestinal disorders. Thus, we should focus on unravelling the molecular and cellular basis of this communication and move from simplistic framing as 'leaky gut'. A mechanistic understanding of gut microbiota modulation of barriers, especially during critical windows of development, could be key to understanding the aetiology of gastrointestinal and neurological disorders.
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Affiliation(s)
- María R Aburto
- APC Microbiome Ireland, University College Cork, Cork, Ireland.
- Department of Anatomy and Neuroscience, School of Medicine, University College Cork, Cork, Ireland.
| | - John F Cryan
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Anatomy and Neuroscience, School of Medicine, University College Cork, Cork, Ireland
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Gao W, Yan Y, Guan Z, Zhang J, Chen W. Effects of Bacillus coagulans TBC169 on gut microbiota and metabolites in gynecological laparoscopy patients. Front Microbiol 2024; 15:1284402. [PMID: 38596369 PMCID: PMC11002114 DOI: 10.3389/fmicb.2024.1284402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Accepted: 03/14/2024] [Indexed: 04/11/2024] Open
Abstract
Objective The primary objective of this study is to investigate the mechanism by which Bacillus coagulans TBC169 accelerates intestinal function recovery in patients who have undergone gynecological laparoscopic surgery, using metabolomics and gut microbiota analysis. Methods A total of 20 subjects were selected and randomly divided into two groups: the intervention group (n = 10) receiving Bacillus coagulans TBC169 Tablets (6 pills, 1.05 × 108 CFU), and the control group (n = 10) receiving placebos (6 pills). After the initial postoperative defecation, fecal samples were collected from each subject to analyze their gut microbiota and metabolic profiles by high-throughput 16S rRNA gene sequencing analysis and untargeted metabonomic. Results There were no statistically significant differences observed in the α-diversity and β-diversity between the two groups; however, in the intervention group, there was a significant reduction in the relative abundance of unclassified_Enterobacteriaceae at the genus level. Furthermore, the control group showed increased levels of Holdemanella and Enterobacter, whereas the intervention group exhibited elevated levels of Intestinimonas. And administration of Bacillus coagulans TBC169 led to variations in 2 metabolic pathways: D-glutamine and D-glutamate metabolism, and arginine biosynthesis. Conclusion This study demonstrated that consuming Bacillus coagulans TBC169 after gynecological laparoscopic surgery might inhibit the proliferation of harmful Enterobacteriaceae; mainly influence 2 pathways including D-glutamine and D-glutamate metabolism, and arginine biosynthesis; and regulate metabolites related to immunity and intestinal motility; which can help regulate immune function, maintain intestinal balance, promote intestinal peristalsis, and thus accelerate the recovery of intestinal function.
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Affiliation(s)
- Weiqi Gao
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, China
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ya Yan
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, China
- School of Pharmacy, Shanxi Medical University, Taiyuan, China
| | - Zhaobo Guan
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, China
- School of Pharmacy, Shanxi Medical University, Taiyuan, China
| | - Jingmin Zhang
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, China
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Weihong Chen
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, China
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- School of Pharmacy, Shanxi Medical University, Taiyuan, China
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20
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Schreiber F, Balas I, Robinson MJ, Bakdash G. Border Control: The Role of the Microbiome in Regulating Epithelial Barrier Function. Cells 2024; 13:477. [PMID: 38534321 PMCID: PMC10969408 DOI: 10.3390/cells13060477] [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: 02/16/2024] [Revised: 03/01/2024] [Accepted: 03/03/2024] [Indexed: 03/28/2024] Open
Abstract
The gut mucosal epithelium is one of the largest organs in the body and plays a critical role in regulating the crosstalk between the resident microbiome and the host. To this effect, the tight control of what is permitted through this barrier is of high importance. There should be restricted passage of harmful microorganisms and antigens while at the same time allowing the absorption of nutrients and water. An increased gut permeability, or "leaky gut", has been associated with a variety of diseases ranging from infections, metabolic diseases, and inflammatory and autoimmune diseases to neurological conditions. Several factors can affect gut permeability, including cytokines, dietary components, and the gut microbiome. Here, we discuss how the gut microbiome impacts the permeability of the gut epithelial barrier and how this can be harnessed for therapeutic purposes.
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Affiliation(s)
| | | | | | - Ghaith Bakdash
- Microbiotica Ltd., Cambridge CB10 1XL, UK; (F.S.); (I.B.); (M.J.R.)
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21
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Liikonen V, Gomez-Gallego C, Kolehmainen M. The effects of whole grain cereals on tryptophan metabolism and intestinal barrier function: underlying factors of health impact. Proc Nutr Soc 2024; 83:42-54. [PMID: 37843435 DOI: 10.1017/s0029665123003671] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2023]
Abstract
This review aims to investigate the relationship between the health impact of whole grains mediated via the interaction with intestinal microbiota and intestinal barrier function with special interest on tryptophan metabolism, focusing on the role of the intestinal microbiota and their impact on barrier function. Consuming various types of whole grains can lead to the growth of different microbiota species, which in turn leads to the production of diverse metabolites, including those derived from tryptophan metabolism, although the impact of whole grains on intestinal microbiota composition results remains inconclusive and vary among different studies. Whole grains can exert an influence on tryptophan metabolism through interactions with the intestinal microbiota, and the presence of fibre in whole grains plays a notable role in establishing this connection. The impact of whole grains on intestinal barrier function is closely related to their effects on the composition and activity of intestinal microbiota, and SCFA and tryptophan metabolites serve as potential links connecting whole grains, intestinal microbiota and the intestinal barrier function. Tryptophan metabolites affect various aspects of the intestinal barrier, such as immune balance, mucus and microbial barrier, tight junction complexes and the differentiation and proliferation of epithelial cells. Despite the encouraging discoveries in this area of research, the evidence regarding the effects of whole grain consumption on intestine-related activity remains limited. Hence, we can conclude that we are just starting to understand the actual complexity of the intestinal factors mediating in part the health impacts of whole grain cereals.
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Affiliation(s)
- Vilma Liikonen
- Department of Clinical Nutrition, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, P.O.Box 1627, 70211 Kuopio, Finland
| | - Carlos Gomez-Gallego
- Department of Clinical Nutrition, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, P.O.Box 1627, 70211 Kuopio, Finland
| | - Marjukka Kolehmainen
- Department of Clinical Nutrition, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, P.O.Box 1627, 70211 Kuopio, Finland
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Homann C, Wilke V, Eckey I, Chuppava B, Kaltschmitt M, Zimmermann A, Visscher C. Rye Bran as a Component in the Diets of Lactating Sows-Effects on Sow and Piglet Performance. Animals (Basel) 2024; 14:380. [PMID: 38338022 PMCID: PMC10854610 DOI: 10.3390/ani14030380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 01/04/2024] [Accepted: 01/17/2024] [Indexed: 02/12/2024] Open
Abstract
From a cost and sustainability perspective, the use of by-products such as rye bran in sow diets is of particular interest. Rye bran has valuable ingredients that have potential benefits for the gut health of sows. The aim of this study was to investigate the effects of including 15% rye bran in the sows' feed on the performance of sows and piglets. The feeding started one week before the farrowing date and ended at weaning. Performance was evaluated by measuring sow (n = 175) and piglet body weight (n = 1372) and sows' backfat thickness (n = 80). These data were additionally used to calculate the colostrum intake of the suckling piglets and the sows' milk production. It was found that there were no differences in the performance parameters between the experimental and control groups. However, this study showed that the piglets with light birth weight (LBW (<1000 g)) and medium birth weight (MBW (1000-1500 g) consumed more colostrum when the sows were fed rye bran (LBW: C/R 203.0 ± 39.2 g/214.3 ± 35.9 g; MBW: 291.3 ± 39.0 g/298.5 ± 36.4 g). It can be concluded that including 15% rye bran in the feed of lactating sows has no obvious negative effects on the performance of sows and piglets. Further studies are needed to evaluate the possible positive effects of rye bran.
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Affiliation(s)
- Christian Homann
- Institute for Animal Nutrition, University of Veterinary Medicine, Foundation, 30559 Hannover, Germany; (C.H.); (I.E.); (C.V.)
| | - Volker Wilke
- Institute for Animal Nutrition, University of Veterinary Medicine, Foundation, 30559 Hannover, Germany; (C.H.); (I.E.); (C.V.)
| | - Isabell Eckey
- Institute for Animal Nutrition, University of Veterinary Medicine, Foundation, 30559 Hannover, Germany; (C.H.); (I.E.); (C.V.)
| | - Bussarakam Chuppava
- Institute for Animal Nutrition, University of Veterinary Medicine, Foundation, 30559 Hannover, Germany; (C.H.); (I.E.); (C.V.)
| | - Martin Kaltschmitt
- Institute of Environmental Technology and Energy Economics, Hamburg University of Technology, 21073 Hamburg, Germany; (M.K.); (A.Z.)
| | - Andreas Zimmermann
- Institute of Environmental Technology and Energy Economics, Hamburg University of Technology, 21073 Hamburg, Germany; (M.K.); (A.Z.)
| | - Christian Visscher
- Institute for Animal Nutrition, University of Veterinary Medicine, Foundation, 30559 Hannover, Germany; (C.H.); (I.E.); (C.V.)
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23
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Alberge J, Mussard E, Al-Ayoubi C, Lencina C, Marrauld C, Cauquil L, Achard CS, Mateos I, Alassane-Kpembi I, Oswald IP, Soler L, Combes S, Beaumont M. Butyrate reduces epithelial barrier dysfunction induced by the foodborne mycotoxin deoxynivalenol in cell monolayers derived from pig jejunum organoids. Gut Microbes 2024; 16:2430424. [PMID: 39572558 PMCID: PMC11587856 DOI: 10.1080/19490976.2024.2430424] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 09/30/2024] [Accepted: 11/11/2024] [Indexed: 11/27/2024] Open
Abstract
The foodborne mycotoxin deoxynivalenol (DON) produced by Fusarium species threats animal and human health through disruption of the intestinal barrier. Targeting the gut microbiota and its products appears as a promising strategy to mitigate DON intestinal toxicity. In this study, we investigated whether the bacterial metabolite butyrate could alleviate epithelial barrier disruption induced by DON. We used a model of cell monolayers derived from porcine jejunum organoids allowing to reproduce the cellular complexity of the intestinal epithelium. Our results show that DON dose-dependently disrupted the epithelial barrier integrity, reduced epithelial differentiation, and altered innate immune defenses. Butyrate attenuated the DON-induced increase in paracellular permeability. Butyrate also prevented epithelial barrier dysfunction triggered by anisomycin, a ribosome inhibitor like DON. Moreover, butyrate partially counteracted the effects of DON on tight junctions (TJP1, OCLN), innate epithelial defenses (PTGS2, CD14, TLR4, TLR5), and absorptive cell functions (CA2, VIL1, NHE3, CFTR). In contrast, butyrate did not prevent the toxic effects of DON on mitochondrial metabolism, proliferation and goblet cell functions. Taken together, our results demonstrate that the bacterial metabolite butyrate is able to reduce DON-induced epithelial barrier disruption.
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Affiliation(s)
- Julie Alberge
- GenPhySE, Université de Toulouse, INRAE, ENVT, Castanet-Tolosan, France
| | - Eloïse Mussard
- GenPhySE, Université de Toulouse, INRAE, ENVT, Castanet-Tolosan, France
- Lallemand Animal Nutrition, Blagnac Cedex, France
| | - Carine Al-Ayoubi
- Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRAE, ENVT, INP-Purpan, Toulouse, France
| | - Corinne Lencina
- GenPhySE, Université de Toulouse, INRAE, ENVT, Castanet-Tolosan, France
| | | | - Laurent Cauquil
- GenPhySE, Université de Toulouse, INRAE, ENVT, Castanet-Tolosan, France
| | | | - Ivan Mateos
- GenPhySE, Université de Toulouse, INRAE, ENVT, Castanet-Tolosan, France
- Lallemand Animal Nutrition, Blagnac Cedex, France
- Departamento de Producción Animal, Universidad de León, León, Spain
| | - Imourana Alassane-Kpembi
- Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRAE, ENVT, INP-Purpan, Toulouse, France
- Centre de recherche en infectiologie porcine et avicole (CRIPA), Faculté de médecine vétérinaire, Université de Montréal, Saint-Hyacinthe, QC, Canada
| | - Isabelle P. Oswald
- Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRAE, ENVT, INP-Purpan, Toulouse, France
| | - Laura Soler
- Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRAE, ENVT, INP-Purpan, Toulouse, France
| | - Sylvie Combes
- GenPhySE, Université de Toulouse, INRAE, ENVT, Castanet-Tolosan, France
| | - Martin Beaumont
- GenPhySE, Université de Toulouse, INRAE, ENVT, Castanet-Tolosan, France
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24
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Ma Y, Shi J, Jia L, He P, Wang Y, Zhang X, Huang Y, Cheng Q, Zhang Z, Dai Y, Xu M, Lei Z. Oregano essential oil modulates colonic homeostasis and intestinal barrier function in fattening bulls. Front Microbiol 2023; 14:1293160. [PMID: 38116527 PMCID: PMC10728825 DOI: 10.3389/fmicb.2023.1293160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Accepted: 11/21/2023] [Indexed: 12/21/2023] Open
Abstract
Oregano essential oil (OEO) primarily contains phenolic compounds and can serve as a dietary supplement for fattening bulls. However, the precise molecular mechanism underlying this phenomenon remains largely elusive. Therefore, this study investigated the impact of adding OEO to diet on the integrity of the intestinal barrier, composition of the colonic microbiome, and production of microbial metabolites in fattening bulls. Our goal was to provide insights into the utilization of plant essential oil products in promoting gastrointestinal health and welfare in animals. We employed amplicon sequencing and metabolome sequencing techniques to investigate how dietary supplementation with OEO impacted the intestinal barrier function in bulls. The inclusion of OEO in the diet resulted in several notable effects on the colon of fattening bulls. These effects included an increase in the muscle thickness of the colon, goblet cell number, short-chain fatty acid concentrations, digestive enzyme activity, relative mRNA expression of intestinal barrier-related genes, and relative expression of the anti-inflammatory factor IL-10. Additionally, α-amylase activity and the relative mRNA expression of proinflammatory cytokines decreased. Moreover, dietary OEO supplementation increased the abundance of intestinal Bacteroides, Coprobacillus, Lachnospiraceae_UCG_001, and Faecalitalea. Metabolomic analysis indicated that OEO primarily increased the levels of 5-aminovaleric acid, 3-methoxysalicylic acid, and creatinine. In contrast, the levels of maltose, lactulose, lactose, and D-trehalose decreased. Correlation analysis showed that altered colonic microbes and metabolites affected intestinal barrier function. Taken together, these results demonstrate that OEO facilitates internal intestinal environmental homeostasis by promoting the growth of beneficial bacteria while inhibiting harmful ones.
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Affiliation(s)
- Yue Ma
- College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, China
| | - Jinping Shi
- College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, China
| | - Li Jia
- College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, China
| | - Pengjia He
- College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, China
| | - Ying Wang
- College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, China
| | - Xiao Zhang
- College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, China
| | - Yongliang Huang
- College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, China
| | - Qiang Cheng
- Gansu Xu Kang Food Co., Ltd., Pingliang, China
| | - Zhao Zhang
- Gansu Huarui Agriculture Co., Ltd., Zhangye, China
| | - Youchao Dai
- College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, China
| | - Meiling Xu
- College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, China
| | - Zhaomin Lei
- College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, China
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25
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Lin L, Zhang K, Xiong Q, Zhang J, Cai B, Huang Z, Yang B, Wei B, Chen J, Niu Q. Gut microbiota in pre-clinical rheumatoid arthritis: From pathogenesis to preventing progression. J Autoimmun 2023; 141:103001. [PMID: 36931952 DOI: 10.1016/j.jaut.2023.103001] [Citation(s) in RCA: 48] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 12/30/2022] [Accepted: 01/31/2023] [Indexed: 03/17/2023]
Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by progressive polyarthritis that leads to cartilage and bone damage. Pre-clinical RA is a prolonged state before clinical arthritis and RA develop, in which autoantibodies (antibodies against citrullinated proteins, rheumatoid factors) can be present due to the breakdown of immunologic self-tolerance. As early treatment initiation before the onset of polyarthritis may achieve sustained remission, optimize clinical outcomes, and even prevent RA progression, the pre-clinical RA stage is showing the prospect to be the window of opportunity for RA treatment. Growing evidence has shown the role of the gut microbiota in inducing systemic inflammation and polyarthritis via multiple mechanisms, which may involve molecular mimicry, impaired intestinal barrier function, gut microbiota-derived metabolites mediated immune regulation, modulation of the gut microbiota's effect on immune cells, intestinal epithelial cells autophagy, and the interaction between the microbiome and human leukocyte antigen alleles as well as microRNAs. Since gut microbiota alterations in pre-clinical RA have been reported, potential therapies for modifying the gut microbiota in pre-clinical RA, including natural products, antibiotic therapy, fecal microbiota transplantation, probiotics, microRNAs therapy, vitamin D supplementation, autophagy inducer-based treatment, prebiotics, and diet, holds great promise for the successful treatment and even prevention of RA via altering ongoing inflammation. In this review, we summarized current studies that include pathogenesis of gut microbiota in RA progression and promising therapeutic strategies to provide novel ideas for the management of pre-clinical RA and possibly preventing arthritis progression.
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Affiliation(s)
- Liyan Lin
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Keyi Zhang
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Qiao Xiong
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Infection Control, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Junlong Zhang
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Bei Cai
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Zhuochun Huang
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Bin Yang
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Bin Wei
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Jie Chen
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.
| | - Qian Niu
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.
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26
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Perreau C, Thabuis C, Verstrepen L, Ghyselinck J, Marzorati M. Ex Vivo Colonic Fermentation of NUTRIOSE ® Exerts Immuno-Modulatory Properties and Strong Anti-Inflammatory Effects. Nutrients 2023; 15:4229. [PMID: 37836513 PMCID: PMC10574048 DOI: 10.3390/nu15194229] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 09/07/2023] [Accepted: 09/27/2023] [Indexed: 10/15/2023] Open
Abstract
NUTRIOSE® (Roquette, Lestrem, France) is a resistant dextrin with well-established prebiotic effects. This study evaluated the indirect effects of pre-digested NUTRIOSE® on host immune response and gut barrier integrity. Fecal samples from eight healthy donors were inoculated in a Colon-on-a-plate® system (ProDigest, Ghent, Belgium) with or without NUTRIOSE® supplementation. Following 48 h fermentation, colonic suspensions were tested in a Caco-2/THP1-Blue™ co-culture system to determine their effects on gut barrier activity (transepithelial electrical resistance) and immune response following lipopolysaccharide stimulation. Additionally, changes in short-chain fatty acid levels (SCFA) and microbial community composition following a 48 h fermentation in the Colon-on-a-plate® system were measured. Across all donors, immune-mediated intestinal barrier damage was significantly reduced with NUTRIOSE®-supplemented colonic suspensions versus blank. Additionally, IL-6 and IL-10 levels were significantly increased, and the level of the neutrophil chemoattractant IL-8 was significantly decreased with NUTRIOSE®-supplemented colonic suspensions versus blank in the co-culture models following lipopolysaccharide stimulation. These beneficial effects of NUTRIOSE® supplementation were likely due to increased acetate and propionate levels and the enrichment of SCFA-producing bacteria. NUTRIOSE® was well fermented by the colonic bacteria of all eight donors and had protective effects on inflammation-induced disruption of the intestinal epithelial barrier and strong anti-inflammatory effects.
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Affiliation(s)
- Caroline Perreau
- Nutrition and Health R&D, Roquette, 1 rue de la Haute Loge, 62136 Lestrem, France; (C.P.); (C.T.)
| | - Clementine Thabuis
- Nutrition and Health R&D, Roquette, 1 rue de la Haute Loge, 62136 Lestrem, France; (C.P.); (C.T.)
| | - Lynn Verstrepen
- ProDigest, Technologiepark 82, 9052 Zwijnaarde, Belgium; (L.V.); (J.G.)
| | - Jonas Ghyselinck
- ProDigest, Technologiepark 82, 9052 Zwijnaarde, Belgium; (L.V.); (J.G.)
| | - Massimo Marzorati
- ProDigest, Technologiepark 82, 9052 Zwijnaarde, Belgium; (L.V.); (J.G.)
- Center for Microbial Ecology and Technology (CMET), Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium
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27
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Zhang Y, Aldamarany WAS, Deng L, Zhong G. Carbohydrate supplementation retains intestinal barrier and ameliorates bacterial translocation in an antibiotic-induced mouse model. Food Funct 2023; 14:8186-8200. [PMID: 37599609 DOI: 10.1039/d3fo01343j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/22/2023]
Abstract
Bacterial translocation (BT), with antibiotic use as an inducer, is associated with increased risk of developing multiple inflammatory disorders, and is closely associated with intestinal barrier integrity. Deacetylated konjac glucomannan (DKGM) and konjac oligo-glucomannan (KOGM) are two of the most widely used derivatives in the food industry. They are structurally and physiologically distinct from konjac glucomannan (KGM), and previous studies have confirmed their prebiotic effects. But whether they play a role in antibiotic-induced BT is unknown. Here, we applied an antibiotic cocktail (Abx) to a mouse model and investigated whether and how KGM and its derivatives function in BT and inflammation response amelioration during and after antibiotics, and which intervention plan is more effective. The results showed that KGM and its derivatives all inhibited BT. The colon tissue lesions caused by BT were largely alleviated, and short-chain fatty acid (SCFA) production was highly improved with the supplementation of carbohydrates. The prolonged intervention plan using KGM and its derivatives was more efficient than intervention only during the Abx administration period. Among the three dietary fibers, KGM behaved best, while DKGM and KOGM behaved equivalently. Additionally, KGM and its derivatives all reduced the inflammatory response accompanying BT, but DKGM may have a direct inhibitory efficacy in inflammation other than that through IL-10, unlike KGM or KOGM.
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Affiliation(s)
- Yuan Zhang
- College of Food Science, Southwest University, Chongqing, 400715, China.
- Chongqing Key Laboratory of Speciality Food Co-Built by Sichuan and Chongqing, Southwest University, Chongqing, 400715, China
| | - Waleed A S Aldamarany
- College of Food Science, Southwest University, Chongqing, 400715, China.
- Food Science and Technology Department, Faculty of Agriculture, Al-Azhar University (Assiut Branch), Assiut 71524, Egypt
| | - Liling Deng
- Chongqing Key Laboratory of High Active Traditional Chinese Drug Delivery System, Chongqing Engineering Research Center of Pharmaceutical Sciences, Chongqing Medical and Pharmaceutical College, Chongqing 401331, China
| | - Geng Zhong
- College of Food Science, Southwest University, Chongqing, 400715, China.
- Chongqing Key Laboratory of Speciality Food Co-Built by Sichuan and Chongqing, Southwest University, Chongqing, 400715, China
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28
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Celano G, Calabrese FM, Riezzo G, D’Attoma B, Ignazzi A, Di Chito M, Sila A, De Nucci S, Rinaldi R, Linsalata M, Vacca M, Apa CA, Angelis MD, Giannelli G, De Pergola G, Russo F. Effects of a Very-Low-Calorie Ketogenic Diet on the Fecal and Urinary Volatilome in an Obese Patient Cohort: A Preliminary Investigation. Nutrients 2023; 15:3752. [PMID: 37686784 PMCID: PMC10490432 DOI: 10.3390/nu15173752] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Revised: 08/23/2023] [Accepted: 08/24/2023] [Indexed: 09/10/2023] Open
Abstract
Several recent studies deepened the strong connection between gut microbiota and obesity. The effectiveness of the very-low-calorie ketogenic diet (VLCKD) has been measured in terms of positive impact on the host homeostasis, but little is known of the modification exerted on the intestinal metabolome. To inspect this complex relationship, we analyzed both fecal and urinary metabolome in terms of volatile organic compounds (VOCs) by the GC-MS method in 25 obese patients that were under VLCKD for eight weeks. Partial least square discriminant analysis evidenced specific urinary and fecal metabolites whose profile can be considered a signature of a partial restore toward the host eubiosis. Specifically, among various keystone VOCs, the decreased concentration of four statistically significant fecal esters (i.e., propanoic acid pentyl ester, butanoic acid hexyl ester, butanoic acid pentyl ester, and pentanoic acid butyl ester) supports the positive effect of VLCKD treatment. Our pilot study results suggest a potential positive effect of VLCKD intervention affecting fecal and urinary volatilome profiles from obese patients. Meta-omics techniques including the study of genes and transcripts will help in developing new interventions useful in preventing or treating obesity and its associated health problems.
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Affiliation(s)
- Giuseppe Celano
- Department of Soil, Plant and Food Science, University of Bari Aldo Moro, 70126 Bari, Italy; (G.C.); (M.V.); (C.A.A.); (M.D.A.)
| | - Francesco Maria Calabrese
- Department of Soil, Plant and Food Science, University of Bari Aldo Moro, 70126 Bari, Italy; (G.C.); (M.V.); (C.A.A.); (M.D.A.)
| | - Giuseppe Riezzo
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology IRCCS “S. de Bellis”, 70013 Castellana Grotte, Italy; (G.R.); (B.D.); (A.I.); (M.L.)
| | - Benedetta D’Attoma
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology IRCCS “S. de Bellis”, 70013 Castellana Grotte, Italy; (G.R.); (B.D.); (A.I.); (M.L.)
| | - Antonia Ignazzi
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology IRCCS “S. de Bellis”, 70013 Castellana Grotte, Italy; (G.R.); (B.D.); (A.I.); (M.L.)
| | - Martina Di Chito
- Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS “S. de Bellis”, 70013 Castellana Grotte, Italy; (M.D.C.); (A.S.); (S.D.N.); (R.R.); (G.D.P.)
| | - Annamaria Sila
- Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS “S. de Bellis”, 70013 Castellana Grotte, Italy; (M.D.C.); (A.S.); (S.D.N.); (R.R.); (G.D.P.)
| | - Sara De Nucci
- Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS “S. de Bellis”, 70013 Castellana Grotte, Italy; (M.D.C.); (A.S.); (S.D.N.); (R.R.); (G.D.P.)
| | - Roberta Rinaldi
- Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS “S. de Bellis”, 70013 Castellana Grotte, Italy; (M.D.C.); (A.S.); (S.D.N.); (R.R.); (G.D.P.)
| | - Michele Linsalata
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology IRCCS “S. de Bellis”, 70013 Castellana Grotte, Italy; (G.R.); (B.D.); (A.I.); (M.L.)
| | - Mirco Vacca
- Department of Soil, Plant and Food Science, University of Bari Aldo Moro, 70126 Bari, Italy; (G.C.); (M.V.); (C.A.A.); (M.D.A.)
| | - Carmen Aurora Apa
- Department of Soil, Plant and Food Science, University of Bari Aldo Moro, 70126 Bari, Italy; (G.C.); (M.V.); (C.A.A.); (M.D.A.)
| | - Maria De Angelis
- Department of Soil, Plant and Food Science, University of Bari Aldo Moro, 70126 Bari, Italy; (G.C.); (M.V.); (C.A.A.); (M.D.A.)
| | - Gianluigi Giannelli
- Scientific Direction, National Institute of Gastroenterology IRCCS “S. de Bellis”, 70013 Castellana Grotte, Italy;
| | - Giovanni De Pergola
- Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS “S. de Bellis”, 70013 Castellana Grotte, Italy; (M.D.C.); (A.S.); (S.D.N.); (R.R.); (G.D.P.)
| | - Francesco Russo
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology IRCCS “S. de Bellis”, 70013 Castellana Grotte, Italy; (G.R.); (B.D.); (A.I.); (M.L.)
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29
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Horrocks V, King OG, Yip AYG, Marques IM, McDonald JAK. Role of the gut microbiota in nutrient competition and protection against intestinal pathogen colonization. MICROBIOLOGY (READING, ENGLAND) 2023; 169:001377. [PMID: 37540126 PMCID: PMC10482380 DOI: 10.1099/mic.0.001377] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/26/2023] [Accepted: 07/25/2023] [Indexed: 08/05/2023]
Abstract
The human gut microbiota can restrict the growth of pathogens to prevent them from colonizing the intestine ('colonization resistance'). However, antibiotic treatment can kill members of the gut microbiota ('gut commensals') and reduce competition for nutrients, making these nutrients available to support the growth of pathogens. This disturbance can lead to the growth and expansion of pathogens within the intestine (including antibiotic-resistant pathogens), where these pathogens can exploit the absence of competitors and the nutrient-enriched gut environment. In this review, we discuss nutrient competition between the gut microbiota and pathogens. We also provide an overview of how nutrient competition can be harnessed to support the design of next-generation microbiome therapeutics to restrict the growth of pathogens and prevent the development of invasive infections.
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Affiliation(s)
- Victoria Horrocks
- Centre for Bacterial Resistance Biology, Department of Life Sciences, Imperial College London, London SW7 2AZ, UK
| | - Olivia G. King
- Centre for Bacterial Resistance Biology, Department of Infectious Disease, Imperial College London, London SW7 2AZ, UK
| | - Alexander Y. G. Yip
- Centre for Bacterial Resistance Biology, Department of Life Sciences, Imperial College London, London SW7 2AZ, UK
| | - Inês Melo Marques
- Centre for Bacterial Resistance Biology, Department of Life Sciences, Imperial College London, London SW7 2AZ, UK
| | - Julie A. K. McDonald
- Centre for Bacterial Resistance Biology, Department of Life Sciences, Imperial College London, London SW7 2AZ, UK
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30
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Kang X, Li C, Liu S, Baldwin RL, Liu GE, Li CJ. Genome-Wide Acetylation Modification of H3K27ac in Bovine Rumen Cell Following Butyrate Exposure. Biomolecules 2023; 13:1137. [PMID: 37509173 PMCID: PMC10377523 DOI: 10.3390/biom13071137] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Revised: 07/12/2023] [Accepted: 07/13/2023] [Indexed: 07/30/2023] Open
Abstract
Butyrate contributes epigenetically to the changes in cellular function and tissue development of the rumen in ruminant animals, which might be achieved by its genetic or epigenetic regulation of gene expression. To explore the role of butyrate on bovine rumen epithelial function and development, this study characterized genome-wide H3K27ac modification changes and super-enhancer profiles in rumen epithelial primary cells (REPC) induced with butyrate by ChIP-seq, and analyzed its effects on gene expression and functional pathways by integrating RNA-seq data. The results showed that genome-wide acetylation modification was observed in the REPC with 94,675 and 48,688 peaks in the butyrate treatment and control group, respectively. A total of 9750 and 5020 genes with increased modification (H3K27ac-gain) and decreased modification (H3K27ac-loss) were detected in the treatment group. The super-enhancer associated genes in the butyrate-induction group were involved in the AMPK signaling pathway, MAPK signaling pathway, and ECM-receptor interaction. Finally, the up-regulated genes (PLCG1, CLEC3B, IGSF23, OTOP3, ADTRP) with H3K27ac gain modification by butyrate were involved in cholesterol metabolism, lysosome, cell adhesion molecules, and the PI3K-Akt signaling pathway. Butyrate treatment has the role of genome-wide H3K27ac acetylation on bovine REPC, and affects the changes in gene expression. The effect of butyrate on gene expression correlates with the acetylation of the H3K27ac level. Identifying genome-wide acetylation modifications and expressed genes of butyrate in bovine REPC cells will expand the understanding of the biological role of butyrate and its acetylation.
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Affiliation(s)
- Xiaolong Kang
- Animal Genomics and Improvement Laboratory, Henry A. Wallace Beltsville Agricultural Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705, USA
- Key Laboratory of Ruminant Molecular and Cellular Breeding, College of Animal Science and Technology, Ningxia University, Yinchuan 750021, China
| | - Chenglong Li
- Key Laboratory of Ruminant Molecular and Cellular Breeding, College of Animal Science and Technology, Ningxia University, Yinchuan 750021, China
| | - Shuli Liu
- Animal Genomics and Improvement Laboratory, Henry A. Wallace Beltsville Agricultural Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705, USA
| | - Ransom L Baldwin
- Animal Genomics and Improvement Laboratory, Henry A. Wallace Beltsville Agricultural Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705, USA
| | - George E Liu
- Animal Genomics and Improvement Laboratory, Henry A. Wallace Beltsville Agricultural Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705, USA
| | - Cong-Jun Li
- Animal Genomics and Improvement Laboratory, Henry A. Wallace Beltsville Agricultural Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705, USA
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Homann C, Eckey I, Chuppava B, Teich K, Buch J, Zimmermann A, Kaltschmitt M, Grone R, Wilke V, Visscher C. Rye and Rye Bran as Components of Diets in Piglet Production-Effects on Salmonella Prevalence. Animals (Basel) 2023; 13:2262. [PMID: 37508038 PMCID: PMC10376390 DOI: 10.3390/ani13142262] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2023] [Revised: 06/30/2023] [Accepted: 07/05/2023] [Indexed: 07/30/2023] Open
Abstract
The nutritional benefits of rye (and therefore rye bran) are mainly due to its high content of fermentable dietary fiber, the non-starch polysaccharides (NSP). Microorganisms in the large intestine are able to convert these into short-chain fatty acids (SCFA), including butyrate. Butyrate strengthens the epithelial barrier function in the colon by nourishing the enterocytes and inhibiting the spread of Salmonella in the intestinal tract. Therefore, the aim of this study was to test under field conditions whether a diet with rye or rye bran as the main ingredient for gilts, sows, and weaned piglets is associated with a lower Salmonella prevalence. Depending on the age groups, between 20-30% rye or between 15-20% rye bran was used in the experimental group. A total of n = 1983 boot swabs, n = 356 fecal samples, and n = 1909 serum samples were examined. The results of this study show that rye or rye bran at the levels used had no apparent effect on the number of positive Salmonella samples. However, the Salmonella OD values in the experimental groups were significantly lower than in the control group. This suggests that the use of rye leads to a lower incidence of infection, but this effect could not be proven from swabs.
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Affiliation(s)
- Christian Homann
- Institute for Animal Nutrition, University of Veterinary Medicine, Foundation, 30559 Hannover, Germany
| | - Isabell Eckey
- Institute for Animal Nutrition, University of Veterinary Medicine, Foundation, 30559 Hannover, Germany
| | - Bussarakam Chuppava
- Institute for Animal Nutrition, University of Veterinary Medicine, Foundation, 30559 Hannover, Germany
| | - Klaus Teich
- SAN Group Biotech Germany GmbH, 49685 Emstek, Germany
| | - Juhle Buch
- SAN Group Biotech Germany GmbH, 49685 Emstek, Germany
| | - Andreas Zimmermann
- Institute of Environmental Technology and Energy Economics, Hamburg University of Technology, 21073 Hamburg, Germany
| | - Martin Kaltschmitt
- Institute of Environmental Technology and Energy Economics, Hamburg University of Technology, 21073 Hamburg, Germany
| | | | - Volker Wilke
- Institute for Animal Nutrition, University of Veterinary Medicine, Foundation, 30559 Hannover, Germany
| | - Christian Visscher
- Institute for Animal Nutrition, University of Veterinary Medicine, Foundation, 30559 Hannover, Germany
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Caetano MAF, Magalhães HIR, Duarte JRL, Conceição LB, Castelucci P. Butyrate Protects Myenteric Neurons Loss in Mice Following Experimental Ulcerative Colitis. Cells 2023; 12:1672. [PMID: 37443707 PMCID: PMC10340616 DOI: 10.3390/cells12131672] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Revised: 06/08/2023] [Accepted: 06/13/2023] [Indexed: 07/15/2023] Open
Abstract
The enteric nervous system is affected by inflammatory bowel diseases (IBD). Gut microbiota ferments dietary fibers and produces short-chain fatty acids, such as Butyrate, which bind to G protein-coupled receptors, such as GPR41, and contribute to maintaining intestinal health. This work aimed to study the GPR41 in myenteric neurons and analyze the effect of Butyrate in mice submitted to experimental ulcerative colitis. The 2, 4, 6 trinitrobenzene sulfonic acid (TNBS) was injected intrarectally in C57BL/6 mice (Colitis). Sham group received ethanol (vehicle). One group was treated with 100 mg/kg of Sodium Butyrate (Butyrate), and the other groups received saline. Animals were euthanized 7 days after colitis induction. Analyzes demonstrated colocalization of GPR41 with neurons immunoreactive (-ir) to nNOS and ChAT-ir and absence of colocalization of the GPR41 with GFAP-ir glia. Quantitative results demonstrated losses of nNOS-ir, ChAT-ir, and GPR41-ir neurons in the Colitis group and Butyrate treatment attenuated neuronal loss. The number of GFAP-ir glia increased in the Colitis group, whereas Butyrate reduced the number of these cells. In addition, morphological alterations observed in the Colitis group were attenuated in the Butyrate group. The presence of GPR41 in myenteric neurons was identified, and the treatment with Butyrate attenuated the damage caused by experimental ulcerative colitis.
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Affiliation(s)
- Marcos A. F. Caetano
- Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil; (M.A.F.C.); (J.R.L.D.); (L.B.C.)
| | - Henrique I. R. Magalhães
- Department of Surgery, School of Veterinary Medicine and Animal Sciences, University of São Paulo, São Paulo 05508-270, Brazil;
| | - Jheniffer R. L. Duarte
- Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil; (M.A.F.C.); (J.R.L.D.); (L.B.C.)
| | - Laura B. Conceição
- Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil; (M.A.F.C.); (J.R.L.D.); (L.B.C.)
| | - Patricia Castelucci
- Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil; (M.A.F.C.); (J.R.L.D.); (L.B.C.)
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Kotla NG, Rochev Y. IBD disease-modifying therapies: insights from emerging therapeutics. Trends Mol Med 2023; 29:241-253. [PMID: 36720660 DOI: 10.1016/j.molmed.2023.01.001] [Citation(s) in RCA: 51] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Revised: 12/19/2022] [Accepted: 01/05/2023] [Indexed: 02/01/2023]
Abstract
Inflammatory bowel disease (IBD) pathogenesis is associated with gut mucosal inflammation, epithelial damage, and dysbiosis leading to a dysregulated gut mucosal barrier. However, the extent and underlying mechanisms remain largely unknown. Current treatment regimens have focused mainly on treating IBD symptoms; however, such treatment strategies do not address mucosal epithelial repair, barrier homeostasis, or intestinal dysbiosis. Although attempts have been made to identify new therapeutic modalities to enhance gut barrier functions, these are at an early developmental stage and have not been wholly successful. We review conventional therapies, the possible relevant role of gut barrier-protecting agents, and biomaterial strategies relating to combination therapies that may pave the way towards developing new therapeutic approaches for IBD.
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Affiliation(s)
- Niranjan G Kotla
- CÚRAM, Science Foundation Ireland (SFI) Research Centre for Medical Devices, University of Galway, Galway, Ireland.
| | - Yury Rochev
- CÚRAM, Science Foundation Ireland (SFI) Research Centre for Medical Devices, University of Galway, Galway, Ireland.
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Gas-Mediated Intestinal Microbiome Regulation Prompts the Methanol Extract of Schizonepetae Spica to Relieve Colitis. Nutrients 2023; 15:nu15030519. [PMID: 36771228 PMCID: PMC9921049 DOI: 10.3390/nu15030519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 01/13/2023] [Accepted: 01/17/2023] [Indexed: 01/21/2023] Open
Abstract
Intestinal dysbiosis plays an important role in the pathogenesis of colitis (UC). Schizonepetae Herba can achieve anti-inflammatory effects as a medicine and food homologous vegetable. Luteolin, eriodictyol, fisetin, and kaempferol are the main anti-inflammatory active compounds obtained through mass spectrometry from the methanol extract of Schizonepetae Spica (JJSM). JJSM intervention resulted in attenuated weight loss, high disease-activity-index score, colon length shortening and colonic pathological damage in DSS-induced colitis mice. Interestingly, hydrogen sulfide (H2S) was inhibited remarkably, which is helpful to elucidate the relationship between active substance and intestinal flora. Furthermore, JJSM administration improved intestinal flora with down-regulating the abundance of harmful bacteria such as Clostridiales and Desulfovibrio and up-regulating the abundance of beneficial bacteria such as Muribaculaceae and Ligolactobacillus and enhanced the production of SCFAs. It is worth noticing that Desulfovibrio is related to the production of intestinal gas H2S. The elevated levels of Desulfovibrio and H2S will hasten the onset of colitis, which is a crucial risk factor for colitis. The results displayed that JJSM could considerably ameliorate colitis by rebuilding H2S-related intestinal flora, which provides a new therapeutic strategy for Schizonepetae Spica to be utilized as a functional food and considered as an emerging candidate for intestinal inflammation.
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35
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The Modulatory Effects of Fatty Acids on Cancer Progression. Biomedicines 2023; 11:biomedicines11020280. [PMID: 36830818 PMCID: PMC9953116 DOI: 10.3390/biomedicines11020280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 01/13/2023] [Accepted: 01/17/2023] [Indexed: 01/21/2023] Open
Abstract
Cancer is the second leading cause of death worldwide and the global cancer burden rises rapidly. The risk factors for cancer development can often be attributed to lifestyle factors, of which an unhealthy diet is a major contributor. Dietary fat is an important macronutrient and therefore a crucial part of a well-balanced and healthy diet, but it is still unclear which specific fatty acids contribute to a healthy and well-balanced diet in the context of cancer risk and prognosis. In this review, we describe epidemiological evidence on the associations between the intake of different classes of fatty acids and the risk of developing cancer, and we provide preclinical evidence on how specific fatty acids can act on tumor cells, thereby modulating tumor progression and metastasis. Moreover, the pro- and anti-inflammatory effects of each of the different groups of fatty acids will be discussed specifically in the context of inflammation-induced cancer progression and we will highlight challenges as well as opportunities for successful application of fatty acid tailored nutritional interventions in the clinic.
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36
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Caetano MAF, Castelucci P. Role of short chain fatty acids in gut health and possible therapeutic approaches in inflammatory bowel diseases. World J Clin Cases 2022; 10:9985-10003. [PMID: 36246826 PMCID: PMC9561599 DOI: 10.12998/wjcc.v10.i28.9985] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Revised: 08/02/2022] [Accepted: 08/25/2022] [Indexed: 02/05/2023] Open
Abstract
Inflammatory bowel diseases (IBDs) are characterized by inflammation in the gastrointestinal tract and include Ulcerative Colitis and Crohn's Disease. These diseases are costly to health services, substantially reduce patients' quality of life, and can lead to complications such as cancer and even death. Symptoms include abdominal pain, stool bleeding, diarrhea, and weight loss. The treatment of these diseases is symptomatic, seeking disease remission. The intestine is colonized by several microorganisms, such as fungi, viruses, and bacteria, which constitute the intestinal microbiota (IM). IM bacteria promotes dietary fibers fermentation and produces short-chain fatty acids (SCFAs) that exert several beneficial effects on intestinal health. SCFAs can bind to G protein-coupled receptors, such as GPR41 and GPR43, promoting improvements in the intestinal barrier, anti-inflammatory, and antioxidant effects. Thus, SCFAs could be a therapeutic tool for IBDs. However, the mechanisms involved in these beneficial effects of SCFAs remain poorly understood. Therefore, this paper aims to provide a review addressing the main aspects of IBDs, and a more detailed sight of SCFAs, focusing on the main effects on different aspects of the intestine with an emphasis on IBDs.
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Affiliation(s)
| | - Patricia Castelucci
- Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508900, SP, Brazil
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37
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Zhang D, Liu J, Cheng H, Wang H, Tan Y, Feng W, Peng C. Interactions between polysaccharides and gut microbiota: A metabolomic and microbial review. Food Res Int 2022; 160:111653. [DOI: 10.1016/j.foodres.2022.111653] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 07/05/2022] [Accepted: 07/06/2022] [Indexed: 12/17/2022]
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Yang H, Qu Y, Gao Y, Sun S, Wu R, Wu J. Research Progress on the Correlation between the Intestinal Microbiota and Food Allergy. Foods 2022; 11:foods11182913. [PMID: 36141041 PMCID: PMC9498665 DOI: 10.3390/foods11182913] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2022] [Revised: 09/08/2022] [Accepted: 09/13/2022] [Indexed: 11/21/2022] Open
Abstract
The increasing incidence of food allergy is becoming a substantial public health concern. Increasing evidence suggests that alterations in the composition of the intestinal microbiota play a part in the development of food allergy. Additionally, the application of probiotics to correct gut microbiota imbalances and regulate food allergy has become a research hotspot. However, the mechanism by which the gut microbiota regulates food allergy and the efficacy of probiotics are still in the preliminary exploration stage, and there are no clear and specific conclusions. The aim of this review is to provide information regarding the immune mechanism underlying food allergy, the correlation between the intestinal microbiota and food allergy, a detailed description of causation, and mechanisms by which the intestinal microbiota regulates food allergy. Subsequently, we highlight how probiotics modulate the gut microbiome–immune axis to alleviate food allergy. This study will contribute to the dovetailing of bacterial therapeutics with immune system in allergic individuals to prevent food allergy and ameliorate food allergy symptoms.
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Affiliation(s)
| | | | | | | | - Rina Wu
- Correspondence: or ; Tel./Fax: +86-24-88487161
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Baky MH, Salah M, Ezzelarab N, Shao P, Elshahed MS, Farag MA. Insoluble dietary fibers: structure, metabolism, interactions with human microbiome, and role in gut homeostasis. Crit Rev Food Sci Nutr 2022; 64:1954-1968. [PMID: 36094440 DOI: 10.1080/10408398.2022.2119931] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Consumption of food rich in dietary fibers (DFs) has been long recognized to exert an overall beneficial effect on human health. This review aims to provide a holistic overview on how IDFs impact human gut health either directly, or through modulation of the gut microbiome. Several databases were searched for collecting papers such as PubMed, Google Scholar, Web of Science, Scopus and Reaxys from 2000 till 2022. Firstly, an overview of the chemical structure of the various IDFs and the pathways employed by gut microbiota for their degradation is provided. The impact of IDFs on microbial community structure and pathogens colonization inside the human gut was discussed. Finally, the impact of IDFs on gut homeostasis and systemic effects at the cellular level, as well as the overall immunological benefits of IDFs consumption were analyzed. IDFs viz., cellulose, hemicellulose, resistant starch, and lignin found enriched in food are discussed for these effects. IDFs were found to induce gut immunity, improve intestinal integrity and mucosal proliferation, and favor adhesion of probiotics and hence improve human health. Also, IDFs were concluded to improve the bioavailability of plant polyphenols and improve their health-related functional roles. Ultimately, dietary fibers processing by modification shows potential to enhance fibers-based functional food production, in addition to increase the economic value and usage of food-rich fibers and their by-products.
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Affiliation(s)
- Mostafa H Baky
- Pharmacognosy Department, College of Pharmacy, Egyptian Russian University, Badr City, Egypt
| | - Mohamed Salah
- Microbiology Department, College of Pharmacy, Port Said University, Port Said, Egypt
| | - Nada Ezzelarab
- Biology Department, School of Sciences & Engineering, The American University in Cairo, New Cairo, Egypt
| | - Ping Shao
- Department of Food Science and Technology, Zhejiang University of Technology, Zhejiang, Hangzhou, PR China
| | - Mostafa S Elshahed
- Department of Microbiology and Molecular Genetics, Oklahoma State University, Stillwater, Oklahoma, USA
| | - Mohamed A Farag
- Pharmacognosy Department, College of Pharmacy, Cairo University, Cairo, Egypt
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40
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Zhou X, Zou Y, Xu Y, Zhang Z, Wu Y, Cao J, Qiu B, Qin X, Han D, Piao X, Wang J, Zhao J. Dietary Supplementation of 25-Hydroxyvitamin D 3 Improves Growth Performance, Antioxidant Capacity and Immune Function in Weaned Piglets. Antioxidants (Basel) 2022; 11:1750. [PMID: 36139824 PMCID: PMC9495450 DOI: 10.3390/antiox11091750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 08/30/2022] [Accepted: 09/01/2022] [Indexed: 11/22/2022] Open
Abstract
This study was conducted to evaluate the effects of 25-hydroxyvitamin D3 (25(OH)VD3) and Vitamin D3 (VD3) supplemented in the diet of weaned piglets on their growth performance, bone quality, intestinal integrity, immune function and antioxidant capacity. A total of 192 weaned piglets were allocated into four groups and they were fed a control diet containing 2000 IU VD3 (negative control, NC), NC + 100 ppm colistin sulfate (positive control, PC), NC + 2000 IU VD3 (VD3) and NC + 2000 IU 25(OH)VD3 (25(OH)VD3). The results showed that 25(OH)VD3 improved the growth performance, bone quality and antioxidase activity of piglets compared with the other groups. Meanwhile, 25(OH)VD3 up-regulated ileal mRNA expressions of tight junction proteins and host defense peptides. The VD3 group had an increased intestinal sIgA content and mRNA expression of pBD-1 compared with the NC group. Both groups of VD3 and 25(OH)VD3 altered the microbial β-diversity compared with the NC group, and 25(OH)VD3 increased ileal concentrations of acetate and butyrate. In conclusion, our findings indicated that a regular dosage of 2000 IU VD3 in the weaned piglets' diet did not achieve optimal antioxidant capacity and immune function. 25(OH)VD3 had better growth performance than VD3 at the same inclusion level, which is associated with the improved intestinal integrity and antioxidant capacity.
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Affiliation(s)
- Xingjian Zhou
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Youwei Zou
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Youhan Xu
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Zeyu Zhang
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Yujun Wu
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Jindang Cao
- Shandong Haineng Bioengineering Co., Ltd., Rizhao 276800, China
| | - Baoqin Qiu
- Shandong Haineng Bioengineering Co., Ltd., Rizhao 276800, China
| | - Xiaoyu Qin
- Shandong Haineng Bioengineering Co., Ltd., Rizhao 276800, China
| | - Dandan Han
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Xiangshu Piao
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Junjun Wang
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Jinbiao Zhao
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
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Hollmann I, Lingens JB, Chuppava B, Wilke V, Abd El-Wahab A, Buch J, Hankel J, Ahmed MFE, Visscher C. In vitro evaluation of sodium butyrate on the growth of three Salmonella serovars derived from pigs at a mild acidic pH value. Front Vet Sci 2022; 9:937671. [PMID: 35958300 PMCID: PMC9360501 DOI: 10.3389/fvets.2022.937671] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 06/28/2022] [Indexed: 11/16/2022] Open
Abstract
Foodborne zoonotic diseases can be transferred into the food chain at the stage of livestock farming. As an emerging public health challenge, practicable reduction measures in porcine health management for Salmonella are constantly being investigated. This in vitro study aimed to determine the influence of six different sodium butyrate (SB) concentrations (0, 5, 10, 20, 40, and 80 mM) on the growth of three different Salmonella enterica serovars at a constant pH value of 6.0, corresponding to conditions in the pig's hindgut. S. Derby and S. Typhimurium, isolated from a pig farm, and S. Typhimurium DSM 19587, which served as control, were used. Broth microdilution assay was applied to record Salmonella growth in the presence of different SB-concentrations over six different incubation periods (0, 1, 2, 4, 6, and 24 h). Results were quantified in the log colony-forming units (log10 CFU/mL). For 1 h incubation, the addition of SB showed no significant differences in the range of initial Salmonella dose of about 5.7 log10 between concentrations (0-80 mM, 5.26 ± 0.10-5.60 ± 0.07 log10, p > 0.05). After 6 h, for SB addition, the range of Salmonella counts was significantly lower compared to no addition of SB (5-80 mM, p < 0.05), 6.78 ± 0.84-7.90 ± 0.10 log10 for 5 mM, and 7.53 ± 0.04-8.71 ± 0.22 log10 for 0 mM. Moreover, for SB concentrations of 40 and 80 mM, no difference in the range of Salmonella counts over 6 h was obtained (5.23 ± 0.11-5.38 ± 0.05 log10, p > 0.05), and minor Salmonella growth was recorded at the earliest after 24 h incubation. Growth rates for varying SB concentrations and incubation times were confirmed in a similar manner for the three serovars. Obtained results suggest that increasing SB concentrations suppress Salmonella growth for concentrations of 5-20 mM over a 6 h incubation period and for 40 and 80 mM over a 24 h incubation period. When transferring these in vitro findings to the porcine organism, it may be assumed that Salmonella reduction can be achieved by increased butyrate content in the chyme of the large intestine.
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Affiliation(s)
- Isabell Hollmann
- Institute for Animal Nutrition, University of Veterinary Medicine Hannover, Foundation, Bischofsholer Damm 15, Hannover, Germany
| | - Jan Berend Lingens
- Institute for Animal Nutrition, University of Veterinary Medicine Hannover, Foundation, Bischofsholer Damm 15, Hannover, Germany
| | - Bussarakam Chuppava
- Institute for Animal Nutrition, University of Veterinary Medicine Hannover, Foundation, Bischofsholer Damm 15, Hannover, Germany
| | - Volker Wilke
- Institute for Animal Nutrition, University of Veterinary Medicine Hannover, Foundation, Bischofsholer Damm 15, Hannover, Germany
| | - Amr Abd El-Wahab
- Institute for Animal Nutrition, University of Veterinary Medicine Hannover, Foundation, Bischofsholer Damm 15, Hannover, Germany
- Department of Nutrition and Nutritional Deficiency Diseases, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt
| | - Juhle Buch
- AniCon Labor GmbH, Höltinghausen, Germany
| | - Julia Hankel
- Institute for Animal Nutrition, University of Veterinary Medicine Hannover, Foundation, Bischofsholer Damm 15, Hannover, Germany
| | - Marwa F. E. Ahmed
- Hygiene and Zoonoses Department, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt
| | - Christian Visscher
- Institute for Animal Nutrition, University of Veterinary Medicine Hannover, Foundation, Bischofsholer Damm 15, Hannover, Germany
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Giromini C, Baldi A, Rebucci R, Lanzoni D, Policardi M, Sundaram TS, Purup S. Role of Short Chain Fatty Acids to Counteract Inflammatory Stress and Mucus Production in Human Intestinal HT29-MTX-E12 Cells. Foods 2022; 11:foods11131983. [PMID: 35804798 PMCID: PMC9265952 DOI: 10.3390/foods11131983] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 06/20/2022] [Accepted: 06/30/2022] [Indexed: 11/18/2022] Open
Abstract
Short chain fatty acids (SCFAs), especially butyrate (BUT), are known to promote intestinal health, but their role in the protection of intestinal barrier integrity is poorly characterized. The aim of the study was to set up an in vitro model of human colon epithelium using HT29-MTX-E12 cells to delineate the potential role of SCFAs under stress conditions. Accordingly, the HT29-MTX-E12 cells were differentiated for 42 days and subsequently exposed to dextran sulphate sodium (DSS). Further, the effects of BUT or its mixture with acetate and propionate (SCFAs-MIX) were tested to study proliferation, epithelial integrity and mucus production. The results showed that the concentration of 10% DSS for 24 h decreased the TEER about 50% compared to the control in HT29-MTX-E12 cells. The pre-treatment on HT29-MTX-E12 cells with BUT or SCFAs-MIX at specific concentrations significantly (p < 0.05) reduced the DSS-induced damage on epithelial cell integrity and permeability. Further, the treatment with specific concentrations of BUT and SCFAs-MIX for 24 h significantly promoted ZO-1, MUC2 and MUC5AC mRNA expression (p < 0.005). The present study demonstrated the suitability of HT29-MTX-E12 cells treated with DSS as an in vitro stress model of inflammatory bowel disease, which enabled us to understand the effect of bioactive SCFAs on the intestinal barrier.
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Affiliation(s)
- Carlotta Giromini
- Department of Veterinary and Animal Science, Università Degli Studi di Milano, Via dell’Università 6, 29600 Lodi, Italy; (A.B.); (R.R.); (D.L.); (T.s.S.)
- CRC, Innovation for Well-Being and Environment, Università Degli Studi di Milano, 20122 Milano, Italy
- Correspondence:
| | - Antonella Baldi
- Department of Veterinary and Animal Science, Università Degli Studi di Milano, Via dell’Università 6, 29600 Lodi, Italy; (A.B.); (R.R.); (D.L.); (T.s.S.)
| | - Raffaella Rebucci
- Department of Veterinary and Animal Science, Università Degli Studi di Milano, Via dell’Università 6, 29600 Lodi, Italy; (A.B.); (R.R.); (D.L.); (T.s.S.)
| | - Davide Lanzoni
- Department of Veterinary and Animal Science, Università Degli Studi di Milano, Via dell’Università 6, 29600 Lodi, Italy; (A.B.); (R.R.); (D.L.); (T.s.S.)
| | - Martina Policardi
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Via Olgettina, 60, 20132 Milano, Italy;
| | - Tamil selvi Sundaram
- Department of Veterinary and Animal Science, Università Degli Studi di Milano, Via dell’Università 6, 29600 Lodi, Italy; (A.B.); (R.R.); (D.L.); (T.s.S.)
| | - Stig Purup
- Department of Animal Science, Aarhus University, DK-8830 Tjele, Denmark;
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Westheim AJF, Stoffels LM, Dubois LJ, van Bergenhenegouwen J, van Helvoort A, Langen RCJ, Shiri-Sverdlov R, Theys J. Fatty Acids as a Tool to Boost Cancer Immunotherapy Efficacy. Front Nutr 2022; 9:868436. [PMID: 35811951 PMCID: PMC9260274 DOI: 10.3389/fnut.2022.868436] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Accepted: 05/11/2022] [Indexed: 12/12/2022] Open
Abstract
Although immunotherapy represents one of the most potent therapeutic anti-cancer approaches, only a limited number of patients shows clinical benefit. Recent evidence suggests that patients' nutritional status plays a major role in immunotherapy outcome. Fatty acids are essential in a balanced diet and well-known to influence the immune response. Moreover, short-chain fatty acids (SCFAs) show beneficial effects in metabolic disorders as well as in cancer and polyunsaturated fatty acids (PUFAs) contribute to body weight and fat free mass preservation in cancer patients. In line with these data, several studies imply a role for SCFAs and PUFAs in boosting the outcome of immunotherapy. In this review, we specifically focus on mechanistic data showing that SCFAs modulate the immunogenicity of tumor cells and we discuss the direct effects of SCFAs and PUFAs on the immune system in the context of cancer. We provide preclinical and clinical evidence indicating that SCFAs and PUFAs may have the potential to boost immunotherapy efficacy. Finally, we describe the challenges and address opportunities for successful application of nutritional interventions focusing on SCFAs and PUFAs to increase the therapeutic potential of immunotherapeutic approaches for cancer.
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Affiliation(s)
- Annemarie J. F. Westheim
- Department of Precision Medicine, GROW-Research School for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, Netherlands
- Department of Genetics and Cell Biology, NUTRIM-School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Netherlands
| | - Lara M. Stoffels
- Department of Precision Medicine, GROW-Research School for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, Netherlands
- Department of Genetics and Cell Biology, NUTRIM-School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Netherlands
| | - Ludwig J. Dubois
- Department of Precision Medicine, GROW-Research School for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, Netherlands
| | - Jeroen van Bergenhenegouwen
- Danone Nutricia Research, Utrecht, Netherlands
- Department of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands
| | - Ardy van Helvoort
- Danone Nutricia Research, Utrecht, Netherlands
- Department of Respiratory Medicine, NUTRIM-School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, Netherlands
| | - Ramon C. J. Langen
- Department of Respiratory Medicine, NUTRIM-School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, Netherlands
| | - Ronit Shiri-Sverdlov
- Department of Genetics and Cell Biology, NUTRIM-School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Netherlands
| | - Jan Theys
- Department of Precision Medicine, GROW-Research School for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, Netherlands
- *Correspondence: Jan Theys
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Yue F, Xu J, Zhang S, Hu X, Wang X, Lü X. Structural features and anticancer mechanisms of pectic polysaccharides: A review. Int J Biol Macromol 2022; 209:825-839. [PMID: 35447258 DOI: 10.1016/j.ijbiomac.2022.04.073] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2021] [Revised: 03/01/2022] [Accepted: 04/09/2022] [Indexed: 02/07/2023]
Abstract
The anticancer activity of pectic polysaccharides (PPs) was proved by numerous studies, and which also indicated that the bioactivity of PPs was closely related to its complicated structures. Based on the summary and analysis about structure characteristics and corresponding enzymatic process of the reported PPs, the anticancer mechanism and related structural features were systematically clarified. It was found that not only the direct effects on the cancer cells by proliferation inhibition or apoptosis, but also the regulation of immune system, gut microbiota and gut metabolism as indirect effects, jointly played important roles in the anticancer of PPs. Nevertheless, during the study of PPs as promising anticancer components, the exact structure-function relationship, digestion process in vivo, and comprehensive action mechanism are still not well understanding. With the unveiling of the proposed issues, it is believed that PPs are promising to be exploited as effective cancer therapy/adjunctive therapy drugs or functional foods.
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Affiliation(s)
- Fangfang Yue
- College of Food Science and Engineering, Northwest Agriculture and Forestry University, Yangling 712100, Shaanxi, China
| | - Jiaxin Xu
- College of Food Science and Engineering, Northwest Agriculture and Forestry University, Yangling 712100, Shaanxi, China
| | - Sitan Zhang
- College of Food Science and Engineering, Northwest Agriculture and Forestry University, Yangling 712100, Shaanxi, China
| | - Xinyu Hu
- College of Food Science and Engineering, Northwest Agriculture and Forestry University, Yangling 712100, Shaanxi, China
| | - Xin Wang
- College of Food Science and Engineering, Northwest Agriculture and Forestry University, Yangling 712100, Shaanxi, China.
| | - Xin Lü
- College of Food Science and Engineering, Northwest Agriculture and Forestry University, Yangling 712100, Shaanxi, China.
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Sodium Butyrate Ameliorates Oxidative Stress-Induced Intestinal Epithelium Barrier Injury and Mitochondrial Damage through AMPK-Mitophagy Pathway. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:3745135. [PMID: 35132348 PMCID: PMC8817854 DOI: 10.1155/2022/3745135] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 01/03/2022] [Accepted: 01/12/2022] [Indexed: 12/12/2022]
Abstract
Sodium butyrate has gained increasing attention for its vast beneficial effects. However, whether sodium butyrate could alleviate oxidative stress-induced intestinal dysfunction and mitochondrial damage of piglets and its underlying mechanism remains unclear. The present study used a hydrogen peroxide- (H2O2-) induced oxidative stress model to study whether sodium butyrate could alleviate oxidative stress, intestinal epithelium injury, and mitochondrial dysfunction of porcine intestinal epithelial cells (IPEC-J2) in AMPK-mitophagy-dependent pathway. The results indicated that sodium butyrate alleviated the H2O2-induced oxidative stress, decreased the level of reactive oxygen species (ROS), increased mitochondrial membrane potential (MMP), mitochondrial DNA (mtDNA), and mRNA expression of genes related to mitochondrial function, and inhibited the release of mitochondrial cytochrome c (Cyt c). Sodium butyrate reduced the protein expression of recombinant NLR family, pyrin domain-containing protein 3 (NLRP3) and fluorescein isothiocyanate dextran 4 kDa (FD4) permeability and increased transepithelial resistance (TER) and the protein expression of tight junction. Sodium butyrate increased the expression of light-chain-associated protein B (LC3B) and Beclin-1, reduced the expression of P62, and enhanced mitophagy. However, the use of AMPK inhibitor or mitophagy inhibitor weakened the protective effect of sodium butyrate on mitochondrial function and intestinal epithelium barrier function and suppressed the induction effect of sodium butyrate on mitophagy. In addition, we also found that after interference with AMPKα, the protective effect of sodium butyrate on IPEC-J2 cells treated with H2O2 was suppressed, indicating that AMPKα is necessary for sodium butyrate to exert its protective effect. In summary, these results revealed that sodium butyrate induced mitophagy by activating AMPK, thereby alleviating oxidative stress, intestinal epithelium barrier injury, and mitochondrial dysfunction induced by H2O2.
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Sun Q, Du M, Kang Y, Zhu MJ. Prebiotic effects of goji berry in protection against inflammatory bowel disease. Crit Rev Food Sci Nutr 2022:1-25. [PMID: 34991393 DOI: 10.1080/10408398.2021.2015680] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The prevalence of inflammatory bowel disease (IBD) is increasing, which is concerning because IBD is a known risk factor for the development of colorectal cancer. Emerging evidence highlights environmental factors, particularly dietary factors and gut microbiota dysbiosis, as pivotal inducers of IBD onset. Goji berry, an ancient tonic food and a nutraceutical supplement, contains a range of phytochemicals such as polysaccharides, carotenoids, and polyphenols. Among these phytochemicals, L. barbarum polysaccharides (LBPs) are the most important functional constituents, which have protective effects against oxidative stress, inflammation, and neurodegeneration. Recently, the beneficial effects of goji berry and associated LBPs consumption were linked to prebiotic effects, which can prevent dysbiosis associated with IBD. This review assessed pertinent literature on the protective effects of goji berry against IBD focusing on the gut microbiota and their metabolites in mediating the observed beneficial effects.
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Affiliation(s)
- Qi Sun
- School of Food Science, Washington State University, Pullman, Washington, USA
| | - Min Du
- Department of Animal Science, Washington State University, Pullman, Washington, USA
| | - Yifei Kang
- School of Food Science, Washington State University, Pullman, Washington, USA
| | - Mei-Jun Zhu
- School of Food Science, Washington State University, Pullman, Washington, USA
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Fan J, Sun J, Li T, Yan X, Jiang Y. Nuciferine prevents hepatic steatosis associated with improving intestinal mucosal integrity, mucus-related microbiota and inhibiting TLR4/MyD88/NF-κB pathway in high-fat induced rats. J Funct Foods 2022. [DOI: 10.1016/j.jff.2021.104859] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
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Lad N, Murphy A, Parenti C, Nelson C, Williams N, Sharpe G, McTernan P. Asthma and obesity: endotoxin another insult to add to injury? Clin Sci (Lond) 2021; 135:2729-2748. [PMID: 34918742 PMCID: PMC8689194 DOI: 10.1042/cs20210790] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 11/29/2021] [Accepted: 12/06/2021] [Indexed: 12/20/2022]
Abstract
Low-grade inflammation is often an underlying cause of several chronic diseases such as asthma, obesity, cardiovascular disease, and type 2 diabetes mellitus (T2DM). Defining the mediators of such chronic low-grade inflammation often appears dependent on which disease is being investigated. However, downstream systemic inflammatory cytokine responses in these diseases often overlap, noting there is no doubt more than one factor at play to heighten the inflammatory response. Furthermore, it is increasingly believed that diet and an altered gut microbiota may play an important role in the pathology of such diverse diseases. More specifically, the inflammatory mediator endotoxin, which is a complex lipopolysaccharide (LPS) derived from the outer membrane cell wall of Gram-negative bacteria and is abundant within the gut microbiota, and may play a direct role alongside inhaled allergens in eliciting an inflammatory response in asthma. Endotoxin has immunogenic effects and is sufficiently microscopic to traverse the gut mucosa and enter the systemic circulation to act as a mediator of chronic low-grade inflammation in disease. Whilst the role of endotoxin has been considered in conditions of obesity, cardiovascular disease and T2DM, endotoxin as an inflammatory trigger in asthma is less well understood. This review has sought to examine the current evidence for the role of endotoxin in asthma, and whether the gut microbiota could be a dietary target to improve disease management. This may expand our understanding of endotoxin as a mediator of further low-grade inflammatory diseases, and how endotoxin may represent yet another insult to add to injury.
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Affiliation(s)
- Nikita Lad
- Department of Biosciences, School of Science and Technology, Nottingham Trent University, Nottingham, NG11 8NS, U.K
| | - Alice M. Murphy
- Department of Biosciences, School of Science and Technology, Nottingham Trent University, Nottingham, NG11 8NS, U.K
| | - Cristina Parenti
- SHAPE Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, NG11 8NS, U.K
| | - Carl P. Nelson
- Department of Biosciences, School of Science and Technology, Nottingham Trent University, Nottingham, NG11 8NS, U.K
| | - Neil C. Williams
- SHAPE Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, NG11 8NS, U.K
| | - Graham R. Sharpe
- SHAPE Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, NG11 8NS, U.K
| | - Philip G. McTernan
- Department of Biosciences, School of Science and Technology, Nottingham Trent University, Nottingham, NG11 8NS, U.K
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How do green and black coffee brews and bioactive interaction with gut microbiome affect its health outcomes? Mining evidence from mechanistic studies, metagenomics and clinical trials. Trends Food Sci Technol 2021. [DOI: 10.1016/j.tifs.2021.11.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Siddiqui MT, Cresci GAM. The Immunomodulatory Functions of Butyrate. J Inflamm Res 2021; 14:6025-6041. [PMID: 34819742 PMCID: PMC8608412 DOI: 10.2147/jir.s300989] [Citation(s) in RCA: 171] [Impact Index Per Article: 42.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2021] [Accepted: 10/15/2021] [Indexed: 12/12/2022] Open
Abstract
The gastrointestinal (GI) system contains many different types of immune cells, making it a key immune organ system in the human body. In the last decade, our knowledge has substantially expanded regarding our understanding of the gut microbiome and its complex interaction with the gut immune system. Short chain fatty acids (SCFA), and specifically butyrate, play an important role in mediating the effects of the gut microbiome on local and systemic immunity. Gut microbial alterations and depletion of luminal butyrate have been well documented in the literature for a number of systemic and GI inflammatory disorders. Although a substantial knowledge gap exists requiring the need for further investigations to determine cause and effect, there is heightened interest in developing immunomodulatory therapies by means of reprogramming of gut microbiome or by supplementing its beneficial metabolites, such as butyrate. In the current review, we discuss the role of endogenous butyrate in the inflammatory response and maintaining immune homeostasis within the intestine. We also present the experimental models and human studies which explore therapeutic potential of butyrate supplementation in inflammatory conditions associated with butyrate depletion.
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Affiliation(s)
- Mohamed Tausif Siddiqui
- Department of Gastroenterology, Hepatology and Human Nutrition, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.,Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA
| | - Gail A M Cresci
- Department of Gastroenterology, Hepatology and Human Nutrition, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.,Department of Pediatric Gastroenterology, Cleveland Clinic, Cleveland, OH, 44195, USA
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