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Noor S, Ali S, Summer M, Riaz A, Nazakat L, Aqsa. Therapeutic Role of Probiotics Against Environmental-Induced Hepatotoxicity: Mechanisms, Clinical Perspectives, Limitations, and Future. Probiotics Antimicrob Proteins 2025; 17:516-540. [PMID: 39316257 DOI: 10.1007/s12602-024-10365-6] [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] [Accepted: 09/10/2024] [Indexed: 09/25/2024]
Abstract
Hepatotoxicity is one of the biggest health challenges, particularly in the context of liver diseases, often aggravated by gut microbiota dysbiosis. The gut-liver axis has been regarded as a key idea in liver health. It indicates that changes in gut flora caused by various hepatotoxicants, including alcoholism, acetaminophen, carbon tetrachloride, and thioacetamide, can affect the balance of the gut's microflora, which may lead to increased dysbiosis and intestinal permeability. As a result, bacterial endotoxins would eventually enter the bloodstream and liver, causing hepatotoxicity and inducing inflammatory reactions. Many treatments, including liver transplantation and modern drugs, can be used to address these issues. However, because of the many side effects of these approaches, scientists and medical experts are still hoping for a therapeutic approach with fewer side effects and more positive results. Thus, probiotics have become well-known as an adjunctive strategy for managing, preventing, or reducing hepatotoxicity in treating liver injury. By altering the gut microbiota, probiotics offer a secure, non-invasive, and economical way to improve liver health in the treatment of hepatotoxicity. Through various mechanisms such as regulation of gut microbiota, reduction of pathogenic overgrowth, suppression of inflammatory mediators, modification of hepatic lipid metabolism, improvement in the performance of the epithelial barrier of the gut, antioxidative effects, and modulation of mucosal immunity, probiotics play their role in the treatment and prevention of hepatotoxicity. This review highlights the mechanistic effects of probiotics in environmental toxicants-induced hepatotoxicity and current findings on this therapeutic approach's experimental and clinical trials.
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Affiliation(s)
- Shehzeen Noor
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, Government College University, Lahore, 54000, Pakistan
| | - Shaukat Ali
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, Government College University, Lahore, 54000, Pakistan.
| | - Muhammad Summer
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, Government College University, Lahore, 54000, Pakistan
| | - Anfah Riaz
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, Government College University, Lahore, 54000, Pakistan
| | - Laiba Nazakat
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, Government College University, Lahore, 54000, Pakistan
| | - Aqsa
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, Government College University, Lahore, 54000, Pakistan
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Chen Y, Zheng K, Leng Y, Zhang Z, Li X, Li X, Ou H, Wen M, Qiu F, Yu H. Alleviating effect of Lactobacillus fermentum E15 on hyperlipidemia and hepatic lipid metabolism in zebrafish fed by a high-fat diet through the production of short-chain fatty acids. Front Nutr 2025; 12:1522982. [PMID: 40098735 PMCID: PMC11911183 DOI: 10.3389/fnut.2025.1522982] [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: 11/05/2024] [Accepted: 02/17/2025] [Indexed: 03/19/2025] Open
Abstract
Introduction Hyperlipidemia is regarded as one of the crucial factors leading to atherosclerosis and other cardiovascular diseases. Gut microbiota plays an important role in regulating host lipid metabolism. Nevertheless, the exact mechanisms behind this remain unclear. Methods In the present study, a hyperlipidemic zebrafish model was established using a high-cholesterol diet (HCD) to evaluate the anti-hyperlipidemic effects of Lactobacillus fermentum E15 (L. fermentum E15). Results Results showed that L. fermentum E15 effectively reduced lipid accumulation in the blood vessels and liver of HCD-fed zebrafish larvae. Meanwhile, L. fermentum E15 improved abnormal lipid levels, and normalized liver enzyme activity. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis revealed that L. fermentum E15 downregulated the expression of sterol regulatory element-binding factor (SREBP-1), peroxisome proliferator-activated receptor-gamma (PPAR-γ), and fatty acid synthase (Fasn), while upregulated peroxisome proliferator-activated receptor-alpha (PPAR-α). Additionally, metabolomic analysis revealed that L. fermentum E15 produced a series of short-chain fatty acids (SCFAs), including acetic acid, propionic acid, butyric acid, and isovaleric acid. Notably, isovaleric acid contributed to the reduction of lipid droplet accumulation in the liver and blood vessels of HCD-fed zebrafish larvae. In contrast, blocking G-protein coupled receptor 43 (GPR43) with pertussis toxin (PTX) abolished the effects of L. fermentum E15 and isovaleric acid on reducing lipid accumulation in HCD-fed zebrafish larvae. RT-qPCR results further suggested that both L. fermentum E15 and isovaleric acid promoted the expression of GPR43 and leptin A, which was inhibited by PTX. Conclusion These findings suggested that L. fermentum E15 alleviates HCD-induced hyperlipidemia by activating GPR43 through SCFAs.
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Affiliation(s)
- Yishu Chen
- Laboratory Animal Center, Guangdong Medical University, Zhanjiang, China
| | - Kangdi Zheng
- Guangdong Longseek Testing Co., Ltd., Guangzhou, China
| | - Yang Leng
- Laboratory Animal Center, Guangdong Medical University, Zhanjiang, China
| | - Zhao Zhang
- Laboratory Animal Center, Guangdong Medical University, Zhanjiang, China
- Guangdong Longseek Testing Co., Ltd., Guangzhou, China
| | - Xiaoling Li
- Laboratory Animal Center, Guangdong Medical University, Zhanjiang, China
| | - Xiaoyan Li
- Laboratory Animal Center, Guangdong Medical University, Zhanjiang, China
| | - Huajun Ou
- Laboratory Animal Center, Guangdong Medical University, Zhanjiang, China
| | - Muhao Wen
- Department of Laboratory Medicine, the Seventh Affiliated Hospital of Southern Medical University, Foshan, China
| | - Feng Qiu
- Department of Laboratory Medicine, the Seventh Affiliated Hospital of Southern Medical University, Foshan, China
| | - Huajun Yu
- Laboratory Animal Center, Guangdong Medical University, Zhanjiang, China
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Zhang J, Hu X, Ma Z. Debranched Lentil Starch-Sodium Alginate-Based Encapsulated Particles of Lacticaseibacillus rhamnosus GG: Morphology, Structural Characterization, In Vitro Release Behavior, and Storage Stability. Foods 2024; 13:4047. [PMID: 39766989 PMCID: PMC11728095 DOI: 10.3390/foods13244047] [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: 11/01/2024] [Revised: 12/10/2024] [Accepted: 12/11/2024] [Indexed: 01/15/2025] Open
Abstract
Starches with different degrees of debranching (DBS30, DBS60, and DBS90) and sodium alginate were used as the wall material for encapsulating particles of Lacticaseibacillus rhamnosus GG (LGG). The structural characteristics of these encapsulated particles were examined, along with the impact of varying levels of debranching on the encapsulation efficiency, the in vitro release of LGG under the simulated gastrointestinal environment, and the storage stability of the encapsulated particles. The results revealed a transformation in the crystalline polymorph from C- to B+V-type following debranching and retrogradation. This process also resulted in a significant decrease in molecular weight and polydispersity index, accompanied by an increase in amylose and resistant starch levels along with the relative crystallinity of the debranched lentil starch. Comparatively, DBS60-LGG and DBS90-LGG exhibited higher encapsulation efficiency and encapsulation yield than UDBS-LGG and DBS30-LGG. Furthermore, these encapsulated particles provided enhanced protection for LGG in both the simulated gastrointestinal environment and the storage process. It can be inferred that a superior encapsulation performance of the debranched lentil starch-sodium alginate-based encapsulated LGG particles was associated with higher debranching levels, a more uniform molecular weight distribution, and a more ordered multi-scale structure of the debranched lentil starch.
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Affiliation(s)
| | | | - Zhen Ma
- College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi’an 710062, China; (J.Z.); (X.H.)
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Tarantino G, Cataldi M, Citro V. Could chronic opioid use be an additional risk of hepatic damage in patients with previous liver diseases, and what is the role of microbiome? Front Microbiol 2024; 15:1319897. [PMID: 39687876 PMCID: PMC11646994 DOI: 10.3389/fmicb.2024.1319897] [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: 10/11/2023] [Accepted: 11/18/2024] [Indexed: 12/18/2024] Open
Abstract
Among illicit drugs, addiction from opioids and synthetic opioids is soaring in an unparalleled manner with its unacceptable amount of deaths. Apart from these extreme consequences, the liver toxicity is another important aspect that should be highlighted. Accordingly, the chronic use of these substances, of which fentanyl is the most frequently consumed, represents an additional risk of liver damage in patients with underlying chronic liver disease. These observations are drawn from various preclinical and clinical studies present in literature. Several downstream molecular events have been proposed, but recent pieces of research strengthen the hypothesis that dysbiosis of the gut microbiota is a solid mechanism inducing and worsening liver damage by both alcohol and illicit drugs. In this scenario, the gut flora modification ascribed to non-alcoholic fatty liver disease performs an additive role. Interestingly enough, HBV and HCV infections impact gut-liver axis. In the end, the authors tried to solicit the attention of operators on this major healthcare problem.
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Affiliation(s)
- Giovanni Tarantino
- Department of Clinical Medicine and Surgery, “Federico II” University Medical School of Naples, Naples, Italy
| | - Mauro Cataldi
- Section of Pharmacology, Department of Neuroscience, Reproductive Sciences and Dentistry, Federico II University of Naples, Naples, Italy
| | - Vincenzo Citro
- Department of General Medicine, “Umberto I” Hospital, Nocera Inferiore, Italy
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Kovynev A, Ying Z, Zhang S, Olgiati E, Lambooij JM, Visentin C, Guigas B, Ducarmon QR, Rensen PCN, Schönke M. Timing Matters: Late, but Not Early, Exercise Training Ameliorates MASLD in Part by Modulating the Gut-Liver Axis in Mice. J Pineal Res 2024; 76:e70003. [PMID: 39539028 DOI: 10.1111/jpi.70003] [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: 09/17/2024] [Revised: 10/10/2024] [Accepted: 10/21/2024] [Indexed: 11/16/2024]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) affects two billion people worldwide and is currently mostly treatable via lifestyle interventions, such as exercise training. However, it is unclear whether the positive effects of exercise are restricted to unique circadian windows. We therefore aimed to study whether the timing of exercise training differentially modulates MASLD development. Twenty weeks old male APOE*3-Leiden.CETP mice were fed a high fat-high cholesterol diet to induce MASLD and treadmill-trained for 1 h five times per week for 12 weeks either early (ZT13; E-RUN) or late (ZT22; L-RUN) in the dark phase while corresponding sedentary groups (E-SED and L-SED) did not. Late, but not early exercise training decreased the MASLD score, body weight, fat mass, and liver triglycerides, accompanied by an altered composition of the gut microbiota. Specifically, only late exercise training increased the abundance of short-chain fatty acid-producing bacterial families and genera, such as Akkermansia, Lachnospiraceae, and Rikenella. To assess the role of the gut microbiota in training-induced effects, the study was repeated and trained (ZT22 only, RUN) or sedentary mice (SED) served as fecal donors for sedentary recipient mice (RUN FMT and SED FMT). Fecal microbiota transplantation reduced liver weight and plasma triglycerides in RUN FMT compared to SED FMT and tended to lower the MASLD score and liver triglycerides. Timing of exercise training is a critical factor for the positive effect on MASLD in this preclinical model, and the effect of late exercise is partially mediated via the gut-liver axis.
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Affiliation(s)
- Artemiy Kovynev
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
- Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Zhixiong Ying
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
- Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Sen Zhang
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
- Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Emanuele Olgiati
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
- Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Joost M Lambooij
- Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center, Leiden, The Netherlands
- Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands
| | - Clara Visentin
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
- Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Bruno Guigas
- Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center, Leiden, The Netherlands
| | - Quinten R Ducarmon
- Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center, Leiden, The Netherlands
| | - Patrick C N Rensen
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
- Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Milena Schönke
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
- Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
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Ghosh S, Ghosh AJ, Islam R, Sarkar S, Saha T. Lactobacillus plantarum KAD protects against high-fat diet-induced hepatic complications in Swiss albino mice: Role of inflammation and gut integrity. PLoS One 2024; 19:e0313548. [PMID: 39531444 PMCID: PMC11556687 DOI: 10.1371/journal.pone.0313548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Accepted: 10/25/2024] [Indexed: 11/16/2024] Open
Abstract
Hepatic complications are the major health issues associated with dietary intake of calorie saturated food e.g. high-fat diet (HFD). Recent studies have revealed the beneficial effects of probiotics in HFD fed mice with hepatic complications. Some probiotic Lactic acid bacteria (LAB) e.g. Lactobacillus plantarum have drawn our attention in managing hepatic complications. Here, we aim to elucidate the protective effects of L. plantarum KAD strain, isolated from ethnic fermented food 'Kinema' in HFD-fed mice as, a preventive approach. Eighteen Swiss albino mice were equally divided into 3 groups: Normal Diet (ND), negative control (HFD), and HFD-fed with oral L. plantarum KAD supplementation (LP). All the experimental groups were subjected to specific diet according to grouping for eight weeks. After completion of the regime, subjects were anesthetized and sacrificed. Organs, blood, and fecal samples were collected and stored appropriately. Physical indices, including body weight gain, organ co-efficients were calculated along with assessment of glycemic, lipidomic, hepatic, oxidative stress, inflammatory, and histological parameters. Gut microbiota analysis was performed using 16s V3-V4 fecal metagenomic profiling, and sequencing were done using Illumina Miseq system. Oral administration of L. plantarum KAD is found to significantly (p<0.05) restore metabolic health by normalizing glycemic, lipidomic, hepatic parameters, oxidative stress and inflammatory parameters. Moreover, LP group (7.08±0.52 mg/g) showed significantly (p<0.001) decreased hepatic triglyceride level compared to HFD group (20.07±1.32 mg/g). L. plantarum KAD improved the adipocytic, and colonic histomorphology with significantly better scoring pattern. LP group (1.83±0.41) showed a significantly (p<0.001) reduced hepatic score compared to negative control group (5.00±0.63), showing reduced hepatosteatosis, and immune infiltration. The strain modulated gut health by altering its microbial composition positively towards normalization. In conclusion, the results of the experiment suggest that prophylactic L. plantarum KAD administration has beneficial effects on the onset of HFD induced hepatic complications in mice. Further studies are needed, on this strain for its clinical use as dietary supplement.
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Affiliation(s)
- Supriyo Ghosh
- Immunology and Microbiology Laboratory, Department of Zoology, University of North Bengal, Siliguri, West Bengal, India
| | - Amlan Jyoti Ghosh
- Immunology and Microbiology Laboratory, Department of Zoology, University of North Bengal, Siliguri, West Bengal, India
| | - Rejuan Islam
- Immunology and Microbiology Laboratory, Department of Zoology, University of North Bengal, Siliguri, West Bengal, India
| | - Sagar Sarkar
- Immunology and Microbiology Laboratory, Department of Zoology, University of North Bengal, Siliguri, West Bengal, India
- Department of Zoology, Siliguri College, Siliguri, West Bengal, India
| | - Tilak Saha
- Immunology and Microbiology Laboratory, Department of Zoology, University of North Bengal, Siliguri, West Bengal, India
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Santos AA, Duarte R, Duarte M, Arella F, Marques V, Roos S, Rodrigues CMP. Impact of Lactobacillaceae supplementation on the multi-organ axis during MASLD. Life Sci 2024; 354:122948. [PMID: 39117140 DOI: 10.1016/j.lfs.2024.122948] [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: 05/20/2024] [Revised: 07/15/2024] [Accepted: 08/05/2024] [Indexed: 08/10/2024]
Abstract
The gut-liver axis plays a pivotal role in maintaining body homeostasis. Disruption of the gut-liver axis is linked to a multitude of diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD). Probiotic strains from the Lactobacillaceae family are commonly used to mitigate experimental MASLD. Over the years, numerous studies have demonstrated the efficacy of these probiotics, often focusing on the outcome of liver disease. This review aims to further understand MASLD as a systemic metabolic dysfunction and to highlight the effects of probiotics on multi-organ axis, including organs such as the gastrointestinal tract, pancreas, muscle, adipose tissue, and the immune system. We specifically discuss evidence on how supplementation with Lactobacillaceae strains may alleviate MASLD by not only restoring liver health but also by modulating the physiology of other organ systems.
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Affiliation(s)
- André A Santos
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Portugal.
| | - Raquel Duarte
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Portugal
| | - Madalena Duarte
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Portugal
| | - Fabiola Arella
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Portugal
| | - Vanda Marques
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Portugal
| | - Stefan Roos
- Department of Molecular Sciences, Uppsala BioCenter, Swedish University of Agricultural Sciences, Sweden
| | - Cecília M P Rodrigues
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Portugal
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Vidya Bernhardt G, Shivappa P, R Pinto J, Ks R, Ramakrishna Pillai J, Kumar Srinivasamurthy S, Paul Samuel V. Probiotics-role in alleviating the impact of alcohol liver disease and alcohol deaddiction: a systematic review. Front Nutr 2024; 11:1372755. [PMID: 39290562 PMCID: PMC11406471 DOI: 10.3389/fnut.2024.1372755] [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: 01/18/2024] [Accepted: 08/05/2024] [Indexed: 09/19/2024] Open
Abstract
Background There are few efficient treatment options for alcohol addiction, which continues to be a serious public health concern. The possible contribution of gut microbiota to the onset and progression of alcohol addiction has been brought to light by recent studies. Probiotics have become a cutting-edge intervention in the treatment of alcohol consumption disorder because of its favorable effects on gut health. The purpose of this systematic review is to assess the body of research on the advantages of probiotics in treating alcoholism and associated neuroinflammatory conditions. Methods To find pertinent research published from January 2012 to 2023, a thorough search of electronic databases, including PubMed, Scopus, Google Scholar and Web of Science, was carried out. Included were studies looking at how probiotics affect neuroinflammation, gut- brain axis regulation, alcohol addiction, and related behaviors. Findings Several investigations have shown how beneficial probiotics are in reducing systemic inflammation and alcoholic liver disease (ALD). Probiotic treatments successfully corrected the imbalance of microbiota, decreased intestinal permeability, and stopped the passage of bacterial constituents such lipopolysaccharides (LPS) into the bloodstream. Additionally, probiotics helped to regulate neurotransmitter pathways, especially those connected to GABA, glutamate, and dopamine, which are intimately linked to behaviors related to addiction. Furthermore, it was shown that probiotics altered the expression of neurotransmitter signaling and dopamine receptors. Conclusion There is strong evidence from this systematic study that probiotics have potential advantages in treating alcohol addiction. The potential of probiotic therapies is demonstrated by the way they modulate important neurotransmitter pathways implicated in addiction, decrease neuroinflammation, and restore the balance of gut flora. To fully investigate the therapeutic potential of probiotics in treating alcohol addiction and enhancing the general wellbeing of those afflicted by this condition, more research is necessary.
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Affiliation(s)
- Grisilda Vidya Bernhardt
- Department of Biochemistry, RAKCOMS, Ras Al-Khaimah Medical and Health Sciences University, Ras Al-Khaimah, United Arab Emirates
| | - Pooja Shivappa
- Department of Biochemistry, RAKCOMS, Ras Al-Khaimah Medical and Health Sciences University, Ras Al-Khaimah, United Arab Emirates
| | - Janita R Pinto
- Department of Biomedical Sciences, Gulf Medical University, Ajman, United Arab Emirates
| | - Rashmi Ks
- Department of Physiology, Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Jayachithra Ramakrishna Pillai
- Department of Pharmaceutical Chemistry, RAKCOPS, Ras Al-Khaimah Medical and Health Sciences University, Ras Al-Khaimah, United Arab Emirates
| | - Suresh Kumar Srinivasamurthy
- Department of Pharmacology, RAKCOMS, Ras Al-Khaimah Medical and Health Sciences University, Ras Al-Khaimah, United Arab Emirates
| | - Vijay Paul Samuel
- Department of Anatomy, RAKCOMS, Ras Al-Khaimah Medical and Health Sciences University, Ras Al-Khaimah, United Arab Emirates
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Victoria Obayomi O, Folakemi Olaniran A, Olugbemiga Owa S. Unveiling the role of functional foods with emphasis on prebiotics and probiotics in human health: A review. J Funct Foods 2024; 119:106337. [DOI: 10.1016/j.jff.2024.106337] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
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Daysita LE, Aulia HR, Pradiva MI, Nandyawati D, Illaningtyas F, Gebrina AD, Mustafawi WZ, Benigna K, Nuraida L, Wulandari N. Characterization and shelf life of synbiotic drink powder from porang ( Amorphophallus muelleri). JOURNAL OF FOOD SCIENCE AND TECHNOLOGY 2024; 61:1272-1282. [PMID: 38910933 PMCID: PMC11189888 DOI: 10.1007/s13197-023-05894-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Revised: 09/19/2023] [Accepted: 11/04/2023] [Indexed: 06/25/2024]
Abstract
Amorphophallus muelleri BI was included in the Araceae family, which is a type of tuber. It is a tuber with high potential due to its abundant bioactive compounds. Amorphophallus muelleri BI flour (AF) contains a high glucomannan and carbon compounds that serve as nutrients for probiotic bacteria. Although Amorphophallus muelleri BI thrives in Indonesia, its utilization rate in the country remains relatively low and haven't been any studies conducted regarding synbiotic powder from AF. The primary objective of this research is to develop a synergistic beverage enriched with varying concentrations of Amorphophallus muelleri BI as a prebiotic and LA as probiotic (synbiotic). The process starts with culture preparation, synbiotic drink process, synbiotic and microencapsulation, includes the examination of solubility, proximate analysis, calorie content, viability, and shelf life. Results showed that the proximate and solubility had no significant effect. Synbiotic drink powder from AF can be produced using spray dry technology. The highest LA growth was observed when augmenting the AF quantity at a 0.4% concentration, which can be seen from the viability parameter with a value of 7.29 log CFU/g. Samples shelf life at -21 and 3 °C with LA viability critical parameter was determined to be 4 days.
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Affiliation(s)
- Lulu Eki Daysita
- Research Center for Food Technology and Processing, National Research and Innovation Agency, Yogyakarta, Indonesia
| | - Hasna Rahma Aulia
- Research Center for Food Technology and Processing, National Research and Innovation Agency, Yogyakarta, Indonesia
| | - Molina Indah Pradiva
- Research Center for Agroindustry, National Research and Innovation Agency, Bogor, Indonesia
| | - Dewi Nandyawati
- Research Center for Agroindustry, National Research and Innovation Agency, Bogor, Indonesia
| | - Fatim Illaningtyas
- Research Center for Food Technology and Processing, National Research and Innovation Agency, Yogyakarta, Indonesia
| | - Amanda Dwi Gebrina
- Research Center for Agroindustry, National Research and Innovation Agency, Bogor, Indonesia
| | - Wike Zahra Mustafawi
- Research Center for Genetic Engineering, National Research and Innovation Agency, Bogor, Indonesia
| | - Kristin Benigna
- Department of Food Science and Technology, Faculty of Agricultural Technology, IPB University, 16680 Bogor, Indonesia
| | - Lilis Nuraida
- Department of Food Science and Technology, Faculty of Agricultural Technology, IPB University, 16680 Bogor, Indonesia
| | - Nur Wulandari
- Department of Food Science and Technology, Faculty of Agricultural Technology, IPB University, 16680 Bogor, Indonesia
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Long C, Zhou X, Xia F, Zhou B. Intestinal Barrier Dysfunction and Gut Microbiota in Non-Alcoholic Fatty Liver Disease: Assessment, Mechanisms, and Therapeutic Considerations. BIOLOGY 2024; 13:243. [PMID: 38666855 PMCID: PMC11048184 DOI: 10.3390/biology13040243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Revised: 04/02/2024] [Accepted: 04/03/2024] [Indexed: 04/28/2024]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a type of metabolic stress liver injury closely related to insulin resistance (IR) and genetic susceptibility without alcohol consumption, which encompasses a spectrum of liver disorders ranging from simple hepatic lipid accumulation, known as steatosis, to the more severe form of steatohepatitis (NASH). NASH can progress to cirrhosis and hepatocellular carcinoma (HCC), posing significant health risks. As a multisystem disease, NAFLD is closely associated with systemic insulin resistance, central obesity, and metabolic disorders, which contribute to its pathogenesis and the development of extrahepatic complications, such as cardiovascular disease (CVD), type 2 diabetes mellitus, chronic kidney disease, and certain extrahepatic cancers. Recent evidence highlights the indispensable roles of intestinal barrier dysfunction and gut microbiota in the onset and progression of NAFLD/NASH. This review provides a comprehensive insight into the role of intestinal barrier dysfunction and gut microbiota in NAFLD, including intestinal barrier function and assessment, inflammatory factors, TLR4 signaling, and the gut-liver axis. Finally, we conclude with a discussion on the potential therapeutic strategies targeting gut permeability and gut microbiota in individuals with NAFLD/NASH, such as interventions with medications/probiotics, fecal transplantation (FMT), and modifications in lifestyle, including exercise and diet.
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Affiliation(s)
- Changrui Long
- Department of Pharmacy, The Seventh Affiliated Hospital of Sun Yat-sen University, Sehenzhen 518107, China;
- School of Pharmacy, Guangdong Medical University, Dongguan 523808, China
| | - Xiaoyan Zhou
- Department of Cardiovascular, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China;
| | - Fan Xia
- Department of Pharmacy, The Seventh Affiliated Hospital of Sun Yat-sen University, Sehenzhen 518107, China;
- Shenzhen Key Laboratory of Chinese Medicine Active Substance Screening and Translational Research, Shenzhen 518107, China
| | - Benjie Zhou
- Department of Pharmacy, The Seventh Affiliated Hospital of Sun Yat-sen University, Sehenzhen 518107, China;
- Shenzhen Key Laboratory of Chinese Medicine Active Substance Screening and Translational Research, Shenzhen 518107, China
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Suntornsaratoon P, Ferraris RP, Ambat J, Antonio JM, Flores J, Jones A, Su X, Gao N, Li WV. Metabolomic and Transcriptomic Correlative Analyses in Germ-Free Mice Link Lacticaseibacillus rhamnosus GG-Associated Metabolites to Host Intestinal Fatty Acid Metabolism and β-Oxidation. J Transl Med 2024; 104:100330. [PMID: 38242234 PMCID: PMC11700500 DOI: 10.1016/j.labinv.2024.100330] [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: 09/15/2023] [Revised: 12/11/2023] [Accepted: 01/09/2024] [Indexed: 01/21/2024] Open
Abstract
Intestinal microbiota confers susceptibility to diet-induced obesity, yet many probiotic species that synthesize tryptophan (trp) actually attenuate this effect, although the underlying mechanisms are unclear. We monocolonized germ-free mice with a widely consumed probiotic Lacticaseibacillus rhamnosus GG (LGG) under trp-free or -sufficient dietary conditions. We obtained untargeted metabolomics from the mouse feces and serum using liquid chromatography-mass spectrometry and obtained intestinal transcriptomic profiles via bulk-RNA sequencing. When comparing LGG-monocolonized mice with germ-free mice, we found a synergy between LGG and dietary trp in markedly promoting the transcriptome of fatty acid metabolism and β-oxidation. Upregulation was specific and was not observed in transcriptomes of trp-fed conventional mice and mice monocolonized with Ruminococcus gnavus. Metabolomics showed that fecal and serum metabolites were also modified by LGG-host-trp interaction. We developed an R-Script-based MEtabolome-TRanscriptome Correlation Analysis algorithm and uncovered LGG- and trp-dependent metabolites that were positively or negatively correlated with fatty acid metabolism and β-oxidation gene networks. This high-throughput metabolome-transcriptome correlation strategy can be used in similar investigations to reveal potential interactions between specific metabolites and functional or disease-related transcriptomic networks.
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Affiliation(s)
- Panan Suntornsaratoon
- Department of Pharmacology, Physiology and Neuroscience, New Jersey Medical School, Rutgers University, Newark, New Jersey; Department of Physiology, Mahidol University, Bangkok, Thailand
| | - Ronaldo P Ferraris
- Department of Pharmacology, Physiology and Neuroscience, New Jersey Medical School, Rutgers University, Newark, New Jersey.
| | - Jayanth Ambat
- Department of Pharmacology, Physiology and Neuroscience, New Jersey Medical School, Rutgers University, Newark, New Jersey
| | - Jayson M Antonio
- Department of Pharmacology, Physiology and Neuroscience, New Jersey Medical School, Rutgers University, Newark, New Jersey
| | - Juan Flores
- Department of Biological Sciences, Life Science Center, Rutgers University, Newark, New Jersey
| | - Abigail Jones
- Department of Pharmacology, Physiology and Neuroscience, New Jersey Medical School, Rutgers University, Newark, New Jersey
| | - Xiaoyang Su
- Department of Medicine, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey
| | - Nan Gao
- Department of Pharmacology, Physiology and Neuroscience, New Jersey Medical School, Rutgers University, Newark, New Jersey; Department of Biological Sciences, Life Science Center, Rutgers University, Newark, New Jersey
| | - Wei Vivian Li
- Department of Statistics, University of California, Riverside, California.
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13
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Li Y, Shi P, Yao K, Lin Q, Wang M, Hou Z, Tang W, Diao H. Diarrhea induced by insufficient fat absorption in weaned piglets: Causes and nutrition regulation. ANIMAL NUTRITION (ZHONGGUO XU MU SHOU YI XUE HUI) 2024; 16:299-305. [PMID: 38371473 PMCID: PMC10869582 DOI: 10.1016/j.aninu.2023.12.004] [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: 04/27/2023] [Revised: 11/07/2023] [Accepted: 12/09/2023] [Indexed: 02/20/2024]
Abstract
Fat is one of the three macronutrients and a significant energy source for piglets. It plays a positive role in maintaining intestinal health and improving production performance. During the weaning period, physiological, stress and diet-related factors influence the absorption of fat in piglets, leading to damage to the intestinal barrier, diarrhea and even death. Signaling pathways, such as fatty acid translocase (CD36), pregnane X receptor (PXR), and AMP-dependent protein kinase (AMPK), are responsible for regulating intestinal fat uptake and maintaining intestinal barrier function. Therefore, this review mainly elaborates on the reasons for diarrhea induced by insufficient fat absorption and related signaling pathways in weaned-piglets, with an emphasis on the intestinal fat absorption disorder. Moreover, we focus on introducing nutritional strategies that can promote intestinal fat absorption in piglets with insufficient fat absorption-related diarrhea, such as lipase, amino acids, and probiotics.
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Affiliation(s)
- Yuying Li
- Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha 410205, China
| | - Pengjun Shi
- Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha 410205, China
| | - Kang Yao
- Institute of Subtropical Agriculture, Chinese Academy of Sciences, Hunan Province Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Changsha 410125, China
| | - Qian Lin
- Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha 410205, China
| | - Mansheng Wang
- Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha 410205, China
| | - Zhenping Hou
- Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha 410205, China
| | - Wenjie Tang
- Animal Breeding and Genetics Key Laboratory of Sichuan Province, Livestock and Poultry Biological Products Key Laboratory of Sichuan Province, Sichuan Animal Science Academy, Sichuan Animtech Feed Co. Ltd, Chengdu 610066, China
| | - Hui Diao
- Animal Breeding and Genetics Key Laboratory of Sichuan Province, Livestock and Poultry Biological Products Key Laboratory of Sichuan Province, Sichuan Animal Science Academy, Sichuan Animtech Feed Co. Ltd, Chengdu 610066, China
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14
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Lapaquette P, Terrat S, Proukhnitzky L, Martine L, Grégoire S, Buteau B, Cabaret S, Rieu A, Bermúdez-Humarán LG, Gabrielle PH, Creuzot-Garcher C, Berdeaux O, Acar N, Bringer MA. Long-term intake of Lactobacillus helveticus enhances bioavailability of omega-3 fatty acids in the mouse retina. NPJ Biofilms Microbiomes 2024; 10:4. [PMID: 38238339 PMCID: PMC10796366 DOI: 10.1038/s41522-023-00474-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Accepted: 12/11/2023] [Indexed: 01/22/2024] Open
Abstract
Omega-3 (n-3) polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA), are required for the structure and function of the retina. Several observational studies indicate that consumption of a diet with relatively high levels of n-3 PUFAs, such as those provided by fish oils, has a protective effect against the development of age-related macular degeneration. Given the accumulating evidence showing the role of gut microbiota in regulating retinal physiology and host lipid metabolism, we evaluated the potential of long-term dietary supplementation with the Gram-positive bacterium Lactobacillus helveticus strain VEL12193 to modulate the retinal n-3 PUFA content. A set of complementary approaches was used to study the impact of such a supplementation on the gut microbiota and host lipid/fatty acid (FA) metabolism. L. helveticus-supplementation was associated with a decrease in retinal saturated FAs (SFAs) and monounsaturated FAs (MUFAs) as well as an increase in retinal n-3 and omega-6 (n-6) PUFAs. Interestingly, supplementation with L. helveticus enriched the retina in C22:5n-3 (docosapentaenoic acid, DPA), C22:6n-3 (DHA), C18:2n-6 (linoleic acid, LA) and C20:3n-6 (dihomo gamma-linolenic acid, DGLA). Long-term consumption of L. helveticus also modulated gut microbiota composition and some changes in OTUs abundance correlated with the retinal FA content. This study provides a proof of concept that targeting the gut microbiota could be an effective strategy to modulate the retinal FA content, including that of protective n-3 PUFAs, thus opening paths for the design of novel preventive and/or therapeutical strategies for retinopathies.
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Affiliation(s)
- Pierre Lapaquette
- Univ. Bourgogne, UMR PAM A 02.102, Institut Agro Dijon, INRAE, F-21000 Dijon, France
| | - Sébastien Terrat
- Agroécologie, Institut Agro, INRAE, Univ. Bourgogne, Univ. Bourgogne Franche-Comté, F-21000, Dijon, France
| | - Lil Proukhnitzky
- Univ. Bourgogne, UMR PAM A 02.102, Institut Agro Dijon, INRAE, F-21000 Dijon, France
- Centre des Sciences du Goût et de l'Alimentation, CNRS, INRAE, Institut Agro, Université de Bourgogne, F-21000, Dijon, France
| | - Lucy Martine
- Centre des Sciences du Goût et de l'Alimentation, CNRS, INRAE, Institut Agro, Université de Bourgogne, F-21000, Dijon, France
| | - Stéphane Grégoire
- Centre des Sciences du Goût et de l'Alimentation, CNRS, INRAE, Institut Agro, Université de Bourgogne, F-21000, Dijon, France
| | - Bénédicte Buteau
- Centre des Sciences du Goût et de l'Alimentation, CNRS, INRAE, Institut Agro, Université de Bourgogne, F-21000, Dijon, France
| | - Stéphanie Cabaret
- ChemoSens Platform, Centre des Sciences du Goût et de l'Alimentation, CNRS, INRAE, Université Bourgogne Franche-Comté, Institut Agro; INRAE, PROBE Research infrastructure, ChemoSens facility, F-21000, Dijon, France
| | - Aurélie Rieu
- Univ. Bourgogne, UMR PAM A 02.102, Institut Agro Dijon, INRAE, F-21000 Dijon, France
| | - Luis G Bermúdez-Humarán
- Micalis Institute, Université Paris-Saclay, INRAE, AgroParisTech, F-78350, Jouy-en-Josas, France
| | - Pierre-Henry Gabrielle
- Centre des Sciences du Goût et de l'Alimentation, CNRS, INRAE, Institut Agro, Université de Bourgogne, F-21000, Dijon, France
- Department of Ophthalmology, University Hospital, F-21000, Dijon, France
| | - Catherine Creuzot-Garcher
- Centre des Sciences du Goût et de l'Alimentation, CNRS, INRAE, Institut Agro, Université de Bourgogne, F-21000, Dijon, France
- Department of Ophthalmology, University Hospital, F-21000, Dijon, France
| | - Olivier Berdeaux
- ChemoSens Platform, Centre des Sciences du Goût et de l'Alimentation, CNRS, INRAE, Université Bourgogne Franche-Comté, Institut Agro; INRAE, PROBE Research infrastructure, ChemoSens facility, F-21000, Dijon, France
| | - Niyazi Acar
- Centre des Sciences du Goût et de l'Alimentation, CNRS, INRAE, Institut Agro, Université de Bourgogne, F-21000, Dijon, France
| | - Marie-Agnès Bringer
- Centre des Sciences du Goût et de l'Alimentation, CNRS, INRAE, Institut Agro, Université de Bourgogne, F-21000, Dijon, France.
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15
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Wu Q, Zhuang M, Guo T, Bao S, Wu S, Ke S, Wang X, Wang A, Zhou Z. Gut microbiota, host lipid metabolism and regulation mechanism of high-fat diet induced mice following different probiotics-fermented wheat bran intervention. Food Res Int 2023; 174:113497. [PMID: 37986413 DOI: 10.1016/j.foodres.2023.113497] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 09/14/2023] [Accepted: 09/22/2023] [Indexed: 11/22/2023]
Abstract
Wheat bran (WB) was fermented by Lactobacillus rhamnosus, Lactobacillus plantarum, Lactobacillus brevis (LAB-FWB), respectively, and their corresponding mechanism of obesity alleviation via gut microbiota and lipid metabolism was investigated. Results indicated LAB-FWB reduced body weight and serum glucose, followed by an improved lipid profile in obese mice compared with WB. All LAB-FWB interventions led to an enriched steroid hormone biosynthesis. LGG-WB significantly up-regulated genes in arachidonic acid metabolism, bile secretion and linoleic acid metabolism. While LB-WB down-regulated genes in PPAR signaling pathway and LP-WB up-regulated genes in linoleic acid metabolism, indicate their different regulation patterns. Furthermore, LAB-FWB reduced Firmicutes/Bacteroidetes ratio and returned HFD-dependent bacteria Colidextribacter and Erysipelatoclostridium to be normalized. Interestingly, LAB-FWB significantly enriched lipid-related pathways, benefiting xanthohumol, prostaglandin F2alpha, LPI 18:2 and lipoamide biosynthesis in lipid metabolic pathway, but not found in WB group. Among them, treatment with LGG-WB exerted the greatest function on alleviating obesity syndromes.
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Affiliation(s)
- Qinghai Wu
- College of Food Science and Engineering, Tianjin University of Science and Technology, Tianjin 300457, China; Biotechnology Research Institute, Inner Mongolia Academy of Agricultural and Animal Husbandry Sciences, Hohhot 010031, China
| | - Min Zhuang
- College of Food Science and Engineering, Tianjin University of Science and Technology, Tianjin 300457, China
| | - Tianlong Guo
- College of Food Science and Engineering, Tianjin University of Science and Technology, Tianjin 300457, China; Biotechnology Research Institute, Inner Mongolia Academy of Agricultural and Animal Husbandry Sciences, Hohhot 010031, China
| | - Sanyue Bao
- Department of Food Engineering, Inner Mongolia Business and Trade Vocational College, Hohhot 010070, China
| | - Sachula Wu
- Biotechnology Research Institute, Inner Mongolia Academy of Agricultural and Animal Husbandry Sciences, Hohhot 010031, China
| | - Sheng Ke
- College of Food Science and Engineering, Tianjin University of Science and Technology, Tianjin 300457, China
| | - Xuanyu Wang
- College of Food Science and Engineering, Tianjin University of Science and Technology, Tianjin 300457, China
| | - Anqi Wang
- College of Food Science and Engineering, Tianjin University of Science and Technology, Tianjin 300457, China
| | - Zhongkai Zhou
- College of Food Science and Engineering, Tianjin University of Science and Technology, Tianjin 300457, China; Gulbali Institure- Agriculture Water Environment, Charles Sturt University, Wagga Wagga, NSW 2678, Australia.
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16
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Quiroz-Eraso S, Rodríguez-Castaño GP, Acosta-González A. Interactions between polyphenols from Theobroma cacao and Lactobacillales to evaluate the potential of a combined strategy for intestinal free-fatty acid removal. Curr Res Food Sci 2023; 7:100594. [PMID: 37790859 PMCID: PMC10543767 DOI: 10.1016/j.crfs.2023.100594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 09/11/2023] [Accepted: 09/14/2023] [Indexed: 10/05/2023] Open
Abstract
Reducing the absorption of lipids in the gastrointestinal tract is one approach used to manage caloric intake in the fight against excessive weight. Biocompounds, such as polyphenols and probiotics, have been used in this regard. However, some studies have reported that polyphenols have both inhibitory and stimulatory effects on bacterial growth. This study aimed to investigate the resistance to polyphenol-rich extracts from Theobroma cacao L. of Lactobacillales isolated from the human fecal microbiota of lean volunteers (with high saturated fat consumption), to further the knowledge of the potential combination of these bioactive compounds. The strains were selected using an improved and affordable strategy that allowed the rapid screening of strains with fat-removing capacity. Among 1400 isolates, two strains, Lactobacillus sp. A1 and Pediococcus acidilactici E1, were selected due to their capacity to remove saturated fats from the culture media similar to the reference strain Lactobacillus sp. JBD301. Both isolated strains differed in their resistance to cocoa polyphenols: the extract did not affect the growth of strain A1, but reduced the growth of strain E1. However, the extract did not affect the level of in vitro fat removal by either strain, confirming the potential use of a combination of bacteria and polyphenols as a promising strategy for the intestinal removal of free fatty acids.
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Affiliation(s)
- Samuel Quiroz-Eraso
- Maestría en Diseño y Gestión de Procesos, Facultad de Ingeniería, Universidad de la Sabana, Km. 7 Autopista Norte, Chia 25001, Colombia
- Bioprospection Research Group (GIBP), Facultad de Ingeniería, Universidad de La Sabana, Km. 7 Autopista Norte, Chia 25001, Colombia
| | - Gina Paola Rodríguez-Castaño
- Bioprospection Research Group (GIBP), Facultad de Ingeniería, Universidad de La Sabana, Km. 7 Autopista Norte, Chia 25001, Colombia
| | - Alejandro Acosta-González
- Bioprospection Research Group (GIBP), Facultad de Ingeniería, Universidad de La Sabana, Km. 7 Autopista Norte, Chia 25001, Colombia
- Unisabana Center for Translational Science, Campus Universitario, Universidad de La Sabana, Km. 7 Autopista Norte, Chia 25001, Colombia
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17
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Guo GJ, Yao F, Lu WP, Xu HM. Gut microbiome and metabolic-associated fatty liver disease: Current status and potential applications. World J Hepatol 2023; 15:867-882. [PMID: 37547030 PMCID: PMC10401411 DOI: 10.4254/wjh.v15.i7.867] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 06/11/2023] [Accepted: 06/30/2023] [Indexed: 07/21/2023] Open
Abstract
Metabolic-associated fatty liver disease (MAFLD) is one of the most common chronic liver diseases worldwide. In recent years, the occurrence rate of MAFLD has been on the rise, mainly due to lifestyle changes, high-calorie diets, and imbalanced dietary structures, thereby posing a threat to human health and creating heavy social and economic burdens. With the development of 16S sequencing and integrated multi-omics analysis, the role of the gut microbiota (GM) and its metabolites in MAFLD has been further recognized. The GM plays a role in digestion, energy metabolism, vitamin synthesis, the prevention of pathogenic bacteria colonisation, and immunoregulation. The gut-liver axis is one of the vital links between the GM and the liver. Toxic substances in the intestine can enter the liver through the portal vascular system when the intestinal barrier is severely damaged. The liver also influences the GM in various ways, such as bile acid circulation. The gut-liver axis is essential in maintaining the body’s normal physiological state and plays a role in the onset and prognosis of many diseases, including MAFLD. This article reviews the status of the GM and MAFLD and summarizes the GM characteristics in MAFLD. The relationship between the GM and MAFLD is discussed in terms of bile acid circulation, energy metabolism, micronutrients, and signalling pathways. Current MAFLD treatments targeting the GM are also listed.
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Affiliation(s)
- Gong-Jing Guo
- Gastroenterology Department of The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People’s Hospital of Shenzhen, Shenzhen 518172, Guangdong Province, China
| | - Fei Yao
- Department of Science and Education, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou 510370, Guangdong Province, China
| | - Wei-Peng Lu
- The First Clinical School, Guangzhou Medical University, Guangzhou 510120, Guangdong Province, China
| | - Hao-Ming Xu
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, Guangdong Province, China
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18
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Chen X, Ran J, Mazhar M, Zhu Y, Lin Y, Qin L, Miao S. The balanced unsaturated fatty acid supplement constituted by woody edible oils improved lipid metabolism and gut microbiota in high-fat diet mice. Front Nutr 2023; 10:1203932. [PMID: 37545586 PMCID: PMC10399753 DOI: 10.3389/fnut.2023.1203932] [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: 04/11/2023] [Accepted: 06/28/2023] [Indexed: 08/08/2023] Open
Abstract
The dietary intervention has demonstrated effectiveness in improving hyperlipidemia and obesity. Woody edible oils are rich in unsaturated fatty acids (UFAs) that could positively affect lipid metabolism. In this study, the blended oil (BLO), a balanced UFA supplement, constituted by Zanthoxylum bungeanum (Chinese Red Pepper) seed oil, walnut (Juglans regia) oil, camellia (Camema oleifera) seed oil and perilla (Perilla frutescens) seed oil was established referring to the Chinese dietary reference intakes, in which the ratios of monounsaturated/polyunsaturated fatty acids and ω-6/ω-3 polyunsaturated fatty acids were 1:1 and 4:1, respectively. The BLO was administrated to KM mice fed a high-fat diet (HFD) by gavage every day at a dose of 3.0 mL/kg·bw for 10 weeks to assess its effects on serum lipid levels, liver antioxidant activities and gut microbial composition. The results showed that the BLO improved hepatic steatosis, liver oxidative stress, and serum lipid levels. Additionally, there was an increased abundance of Lactobacillus, Allobaculum, and Blautia, along with a decreased abundance of Staphylococcus in cecal contents. These changes were found to be positively correlated with the metabolic improvements, as indicated by Spearman's correlation analysis. These findings implied the practicality of the balanced unsaturated fatty acid consumption in preventing hyperlipidemia and obesity.
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Affiliation(s)
- Xi Chen
- Key Laboratory of Plant Resource Conservation and Germplasm Innovation in Mountainous Region (Ministry of Education), College of Life Sciences/Institute of Agro-Bioengineering, Guizhou University, Guiyang, China
- Department of Laboratory Medicine, Affiliated Jinyang Hospital of Guizhou Medical University, Guiyang, China
| | - Jingqi Ran
- School of Liquor and Food Engineering, Guizhou University, Guiyang, China
| | - Muhammad Mazhar
- Key Laboratory of Plant Resource Conservation and Germplasm Innovation in Mountainous Region (Ministry of Education), College of Life Sciences/Institute of Agro-Bioengineering, Guizhou University, Guiyang, China
- School of Liquor and Food Engineering, Guizhou University, Guiyang, China
| | - Yong Zhu
- School of Liquor and Food Engineering, Guizhou University, Guiyang, China
| | - Yichen Lin
- Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork, Ireland
| | - Likang Qin
- Key Laboratory of Plant Resource Conservation and Germplasm Innovation in Mountainous Region (Ministry of Education), College of Life Sciences/Institute of Agro-Bioengineering, Guizhou University, Guiyang, China
- School of Liquor and Food Engineering, Guizhou University, Guiyang, China
| | - Song Miao
- Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork, Ireland
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19
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Aziz M, Hemeda SA, Albadrani GM, Fadl SE, Elgendey F. Ameliorating effect of probiotic on nonalcoholic fatty liver disease and lipolytic gene expression in rabbits. Sci Rep 2023; 13:6312. [PMID: 37072469 PMCID: PMC10113232 DOI: 10.1038/s41598-023-32584-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Accepted: 03/29/2023] [Indexed: 05/03/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a condition that affects about 24% of people worldwide. Increased liver fat, inflammation, and, in the most severe cases, cell death are all characteristics of NAFLD. However, NAFLD pathogenesis and therapy are still not clear enough. Thus, this study aimed to determine the effect of a high-cholesterol diet (HCD) inducing NAFLD on lipolytic gene expression, liver function, lipid profile, and antioxidant enzymes in rabbits and the modulatory effects of probiotic Lactobacillus acidophilus (L. acidophilus) on it. A total of 45 male New Zealand white rabbits, eight weeks old, were randomly divided into three groups of three replicates (5 rabbits/replicate). Rabbits in group I were given a basal diet; rabbits in group II were given a high-cholesterol diet that caused NAFLD; and rabbits in group III were given a high-cholesterol diet as well as probiotics in water for 8 weeks. The results showed that a high-cholesterol diet caused hepatic vacuolation and upregulated the genes for lipoprotein lipase (LPL), hepatic lipase (HL), and cholesteryl ester transfer protein (CETP). Downregulated low-density lipoprotein receptor (LDLr) gene, increased liver enzymes [alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH)], cholesterol, triglycerides (TG), low-density lipoprotein (LDL), glucose, and total bilirubin. On the other hand, it decreased high-density lipoprotein (HDL), total protein, albumin, and liver antioxidants [glutathione peroxidase (GPx), catalase (CAT), reduced glutathione (GSH), and superoxide dismutase (SOD)]. Supplementing with probiotics helped to return all parameters to normal levels. In conclusion, probiotic supplementation, especially L. acidophilus, protected against NAFLD, and restored lipolytic gene expression, liver functions, and antioxidants to normal levels.
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Affiliation(s)
- Marina Aziz
- Genetics and Genetic Engineering, Department of Animal Wealth Development, Faculty of Veterinary Medicine, Benha University, Banha, Egypt
| | - Shabaan A Hemeda
- Department of Animal Husbandry and Animal Wealth Development, Faculty of Veterinary Medicine, Alexandria University, Alexandria, Egypt
| | - Ghadeer M Albadrani
- Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh, 11671, Saudi Arabia
| | - Sabreen E Fadl
- Biochemistry Department, Faculty of Veterinary Medicine, Matrouh University, Matrouh, Egypt.
| | - Fatma Elgendey
- Genetics and Genetic Engineering, Department of Animal Wealth Development, Faculty of Veterinary Medicine, Benha University, Banha, Egypt
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20
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Kuraji R, Shiba T, Dong TS, Numabe Y, Kapila YL. Periodontal treatment and microbiome-targeted therapy in management of periodontitis-related nonalcoholic fatty liver disease with oral and gut dysbiosis. World J Gastroenterol 2023; 29:967-996. [PMID: 36844143 PMCID: PMC9950865 DOI: 10.3748/wjg.v29.i6.967] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Revised: 11/14/2022] [Accepted: 01/30/2023] [Indexed: 02/10/2023] Open
Abstract
A growing body of evidence from multiple areas proposes that periodontal disease, accompanied by oral inflammation and pathological changes in the microbiome, induces gut dysbiosis and is involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). A subgroup of NAFLD patients have a severely progressive form, namely nonalcoholic steatohepatitis (NASH), which is characterized by histological findings that include inflammatory cell infiltration and fibrosis. NASH has a high risk of further progression to cirrhosis and hepatocellular carcinoma. The oral microbiota may serve as an endogenous reservoir for gut microbiota, and transport of oral bacteria through the gastro-intestinal tract can set up a gut microbiome dysbiosis. Gut dysbiosis increases the production of potential hepatotoxins, including lipopolysaccharide, ethanol, and other volatile organic compounds such as acetone, phenol and cyclopentane. Moreover, gut dysbiosis increases intestinal permeability by disrupting tight junctions in the intestinal wall, leading to enhanced translocation of these hepatotoxins and enteric bacteria into the liver through the portal circulation. In particular, many animal studies support that oral administration of Porphyromonas gingivalis, a typical periodontopathic bacterium, induces disturbances in glycolipid metabolism and inflammation in the liver with gut dysbiosis. NAFLD, also known as the hepatic phenotype of metabolic syndrome, is strongly associated with metabolic complications, such as obesity and diabetes. Periodontal disease also has a bidirectional relationship with metabolic syndrome, and both diseases may induce oral and gut microbiome dysbiosis with insulin resistance and systemic chronic inflammation cooperatively. In this review, we will describe the link between periodontal disease and NAFLD with a focus on basic, epidemiological, and clinical studies, and discuss potential mechanisms linking the two diseases and possible therapeutic approaches focused on the microbiome. In conclusion, it is presumed that the pathogenesis of NAFLD involves a complex crosstalk between periodontal disease, gut microbiota, and metabolic syndrome. Thus, the conventional periodontal treatment and novel microbiome-targeted therapies that include probiotics, prebiotics and bacteriocins would hold great promise for preventing the onset and progression of NAFLD and subsequent complications in patients with periodontal disease.
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Affiliation(s)
- Ryutaro Kuraji
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo 102-0071, Japan
- Department of Orofacial Sciences, University of California San Francisco, San Francisco, CA 94143, United States
| | - Takahiko Shiba
- Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA 02115, United States
- Department of Periodontology, Tokyo Medical and Dental University, Tokyo 113-8549, Japan
| | - Tien S Dong
- The Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Department of Medicine, University of California David Geffen School of Medicine, Los Angeles, CA 90095, United States
| | - Yukihiro Numabe
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo 102-8159, Japan
| | - Yvonne L Kapila
- Department of Orofacial Sciences, University of California San Francisco, San Francisco, CA 94143, United States
- Sections of Biosystems and Function and Periodontics, Professor and Associate Dean of Research, Felix and Mildred Yip Endowed Chair in Dentistry, University of California Los Angeles, Los Angeles, CA 90095, United States
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21
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Yu X, Wang Y, Lai J, Song T, Duan J. Comparative efficacy of exercise training processes in improving nonalcoholic fatty liver disease: a systematic review and meta-analysis. Ir J Med Sci 2023; 192:131-142. [PMID: 35366201 DOI: 10.1007/s11845-022-02988-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Accepted: 03/17/2022] [Indexed: 02/04/2023]
Abstract
OBJECTIVES This systematic review and meta-analysis aimed to evaluate the efficacy of exercise training in patients with nonalcoholic fatty liver disease (NAFLD). METHODS We searched PubMed, Cochrane Library, Web of Science, and Embase for relevant research from January 2001 to December 2021. The efficacy of exercise training was analyzed. RESULTS A total of 21 articles, involving 1733 patients, were included. Exercise training, including resistance training, aerobic exercise training, and high-intensity training, showed the efficacy in reducing weight (MD = 3.46, 95% CI [1.94, 4.98]), BMI (MD = 0.89, 95% CI [0.17, 1.61]), and ALT (MD = 6.66, 95% CI [3.27, 10.04]) and AST (MD = 3.14, 95% CI [0.35, 5.93]) levels in patients with NAFLD. When the exercise training lasted for ≥ 20 weeks, the total cholesterol (TC) (MD = 0.13, 95% CI [0.04, 0.22]), triglyceride (TG) (MD = 0.29, 95% CI [0.12, 0.47]), and blood glucose (GLU) (MD = - 0.18, 95% CI [0.10, 0.26]) levels significantly reduced. Compared with the exercise training group, the exercise training combined with probiotics group showed more efficiency in reducing the ALT, AST, TG, and TC levels. However, the exercise training combined with a hypoglycemic agent group showed no obvious efficiency compared with the exercise training group. CONCLUSION Exercise training can improve NAFLD. The improvement was more obvious when exercise was performed for ≥ 20 weeks. Probiotics may enhance the efficiency of exercise training.
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Affiliation(s)
- Xue Yu
- Department of Hepatology, The Sixth People's Hospital of Qingdao, Fushun road, no 9, Shandong Province, 266033, China
| | - Yan Wang
- Department of Hepatology, The Sixth People's Hospital of Qingdao, Fushun road, no 9, Shandong Province, 266033, China
| | - Jianming Lai
- Department of Hepatology, The Sixth People's Hospital of Qingdao, Fushun road, no 9, Shandong Province, 266033, China
| | - Ting Song
- Department of Hepatology, The Sixth People's Hospital of Qingdao, Fushun road, no 9, Shandong Province, 266033, China
| | - Jianping Duan
- Department of Hepatology, The Sixth People's Hospital of Qingdao, Fushun road, no 9, Shandong Province, 266033, China.
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22
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Lack of Faecalibacterium prausnitzii and Bifidobacterium is associated with a higher risk of metabolic associated fatty liver disease in young-onset type 2 diabetes. Int J Diabetes Dev Ctries 2023. [DOI: 10.1007/s13410-022-01161-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
Abstract
Background
The incidence of comorbidity between type 2 diabetes mellitus (T2DM) and metabolic-associated fatty liver disease (MAFLD) is high, and patients tend to be younger. When people develop metabolic diseases such as T2DM and MAFLD, the original homeostasis of the gut microbiota in the body is disrupted, and gut flora drift occurs. This study investigated the relationship between the number of gut flora and MAFLD in young-onset T2DM.
Methods
This retrospective study analyzed 44 adolescent T2DM patients who were divided into a non-MAFLD group and a MAFLD group. Anthropometric measurements, clinical and biochemical markers, inflammatory markers, thyroid function assessments, and stool specimens were collected. Real-time PCR was performed to quantify several important gut flora constituents at the genus level. Student’s t-test and the chi-square test were applied for group comparisons, and binary regression models were used to explore the relationship between gut flora and MAFLD in young-onset T2DM.
Results
Among the 44 subjects, 26 (59.1%) were diagnosed with MAFLD, and 18 (40.9%) were not. Compared with the non-MAFLD group, body mass index (BMI), abdominal circumference, and levels of blood uric acid and thyroid stimulating hormone (TSH) in the MAFLD group were significantly increased, and age level and high-density lipoprotein cholesterol (HDL-C) were significantly decreased (p < 0.05). Compared with the non-MAFLD group, the abundance of Faecalibacterium prausnitzii and Bifidobacterium in the MAFLD group was significantly reduced, and the abundance of Enterococcus and Lactobacillus was significantly increased (p < 0.05). In the multivariate regression analysis, Faecalibacterium prausnitzii and Bifidobacterium were independent protective factors for MAFLD in young-onset T2DM, after excluding confounding factors.
Conclusion
In young-onset T2DM, there was a difference in gut flora between patients with MAFLD and those without MAFLD. Faecalibacterium prausnitzii and Bifidobacterium were independent protective factors for MAFLD in young-onset T2DM.
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23
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Muacevic A, Adler JR, Shahid M, Musleh M, Shabbir E. Endotipsitis in an Immunocompetent Patient With Lactobacillus Bacteremia. Cureus 2023; 15:e33405. [PMID: 36751240 PMCID: PMC9899101 DOI: 10.7759/cureus.33405] [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] [Accepted: 01/05/2023] [Indexed: 01/07/2023] Open
Abstract
Transjugular intrahepatic portosystemic shunt (TIPS) is a procedure commonly performed to decompress portal venous pressure since the early 1990s. Endotipsitis, which refers to persistent bacteremia caused by endovascular infection of the TIPS stent, is a rare but serious complication of this procedure. Very few cases of endotipsitis have been reported worldwide. We report the case of an immunocompetent patient diagnosed with endotipsitis, an atypical risk factor for Lactobacillus infection. This case report adds to the literature on underreported complications of TIPS, highlighting an urgent need for introducing clinical practice guidelines regarding the definition, diagnosis, and treatment of endotipsitis.
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24
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Zhao L, Qiu Y, Zhang P, Wu X, Zhao Z, Deng X, Yang L, Wang D, Yuan G. Gut microbiota mediates positive effects of liraglutide on dyslipidemia in mice fed a high-fat diet. Front Nutr 2022; 9:1048693. [PMID: 36643973 PMCID: PMC9835552 DOI: 10.3389/fnut.2022.1048693] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Accepted: 11/14/2022] [Indexed: 12/30/2022] Open
Abstract
Except for improving glycemic control, liraglutide, one of the glucagon-like peptide-1 receptor agonists, has exerted promising therapeutic effects for dyslipidemia. It has been proved that gut microbiota plays a dramatic role in regulating lipid metabolism. This study aims to explore whether liraglutide could improve dyslipidemia by modulating the gut microbiota in mice fed a high-fat diet (HFD). The C57BL/6 mice were fed a HFD to establish an animal model of dyslipidemia, and then administered with liraglutide or normal saline (NS) for 12 weeks. Indices of glucolipid metabolism were evaluated. Gut microbiota of the mice was analyzed by 16S rRNA gene sequencing. Compared with HFD group, liraglutide significantly alleviated weight, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) levels, meanwhile elevating high-density lipoprotein cholesterol (HDL) levels (all p < 0.05). The gut microbiota analysis revealed that liraglutide greatly reduced the relative abundance of Firmicutes and augmented that of Bacteroidetes, with a concomitant drop in the Firmicutes/Bacteroidetes ratio. Meanwhile, liraglutide dramatically changed the overall composition, promoted the growth of beneficial microbes (Akkermansia, Lactobacillus, Parabacteroides, Oscillospira, etc.), and inhibited the growth of harmful microbes (AF12, Shigella, Proteobacteria, Xenorhabdus, etc.). Especially, the relative abundance of Akkermansia increased the most after liraglutide treatment. Correlation analysis suggested that TC and LDL were positively correlated with some harmful bacteria, and negatively associated with beneficial bacteria. This study confirmed that liraglutide had a certain therapeutic effect on dyslipidemia in HFD-fed mice and could regulate the composition of the gut microbiota associated with lipid metabolism, especially Akkermansia. Thus, affecting gut microbiota might be a potential mechanism of liraglutide in attenuating dyslipidemia.
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Affiliation(s)
- Li Zhao
- Department of Endocrinology and Metabolism, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China,*Correspondence: Li Zhao,
| | - Yue Qiu
- Department of Endocrinology and Metabolism, The First People’s Hospital of Lianyungang, Lianyungang, Jiangsu, China
| | - Panpan Zhang
- Department of Endocrinology, Taicang Hospital of Traditional Chinese Medicine, Taicang, Jiangsu, China
| | - Xunan Wu
- Department of Endocrinology and Metabolism, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Zhicong Zhao
- Department of Endocrinology and Metabolism, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Xia Deng
- Department of Endocrinology and Metabolism, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Ling Yang
- Department of Endocrinology and Metabolism, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Dong Wang
- Department of Endocrinology and Metabolism, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Guoyue Yuan
- Department of Endocrinology and Metabolism, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China,Guoyue Yuan,
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25
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Werlinger P, Nguyen HT, Gu M, Cho JH, Cheng J, Suh JW. Lactobacillus reuteri MJM60668 Prevent Progression of Non-Alcoholic Fatty Liver Disease through Anti-Adipogenesis and Anti-inflammatory Pathway. Microorganisms 2022; 10:2203. [PMID: 36363795 PMCID: PMC9696116 DOI: 10.3390/microorganisms10112203] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 10/18/2022] [Accepted: 11/04/2022] [Indexed: 08/26/2023] Open
Abstract
Non-alcoholic fatty liver disease (NALFD) is a disease characterized by liver steatosis. The liver is a key organ involved in the metabolism of fat, protein, and carbohydrate, enzyme activation, and storage of glycogen, which is closely related to the intestine by the bidirectional relation of the gut-liver axis. Abnormal intestinal microbiota composition can affect energy metabolism and lipogenesis. In this experiment, we investigated the beneficial effect of Lactobacillus reuteri MJM60668 on lipid metabolism and lipogenesis. C57BL/6 mice were fed a high-fat diet (HFD) and orally administrated with MJM60668. Our results showed that mice treated with MJM60668 significantly decreased liver weight and liver/body weight ratio, without affecting food intake. Serum levels of ALT, AST, TG, TCHO, and IL-1β in mice fed with MJM60668 were decreased compared to the HFD group. Investigation of gene and protein expression on the lipogenesis and lipid metabolism showed that the expression of ACC, FAS, and SREBP was decreased, and PPARα and CPT was increased. Furthermore, an increase of adiponectin in serum was shown in our experiment. Moreover, serum IL-1β level was also significantly decreased in the treated mice. These results suggested that MJM60668 can strongly inhibit lipogenesis, enhance fatty acid oxidation, and suppress inflammation. Additionally, supplementation of MJM60668 increased the proportion of Akkermansiaceae and Lachnospiracea, confirming a potential improvement of gut microbiota, which is related to mucus barrier and decrease of triglycerides levels.
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Affiliation(s)
- Pia Werlinger
- Interdisciplinary Program of Biomodulation, Myongji University, Yongin 17058, Korea
| | - Huong Thi Nguyen
- Interdisciplinary Program of Biomodulation, Myongji University, Yongin 17058, Korea
| | - Mingkun Gu
- Interdisciplinary Program of Biomodulation, Myongji University, Yongin 17058, Korea
| | - Joo-Hyung Cho
- Myongji Bioefficacy Research Center, Myongji University, Yongin 17058, Korea
| | - Jinhua Cheng
- Interdisciplinary Program of Biomodulation, Myongji University, Yongin 17058, Korea
- Myongji Bioefficacy Research Center, Myongji University, Yongin 17058, Korea
| | - Joo-Won Suh
- Interdisciplinary Program of Biomodulation, Myongji University, Yongin 17058, Korea
- Myongji Bioefficacy Research Center, Myongji University, Yongin 17058, Korea
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26
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Lactobacillus sakei MJM60958 as a Potential Probiotic Alleviated Non-Alcoholic Fatty Liver Disease in Mice Fed a High-Fat Diet by Modulating Lipid Metabolism, Inflammation, and Gut Microbiota. Int J Mol Sci 2022; 23:ijms232113436. [PMID: 36362221 PMCID: PMC9658623 DOI: 10.3390/ijms232113436] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 10/28/2022] [Accepted: 10/31/2022] [Indexed: 11/06/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a common liver disease with a rapidly increasing number of cases worldwide. This study aimed to evaluate the effects of Lactobacillus sakei MJM60958 (MJM60958) on NAFLD in vitro and in vivo. In in vitro tests, MJM60958 significantly inhibited lipid accumulation by 46.79% in HepG2 cells stimulated with oleic acid and cholesterol (OA-C). Moreover, MJM60958 showed safe and probiotic characteristics in vitro. In the animal study, MJM60958 administration in a high-fat diet-induced NAFLD mouse model significantly reduced body weight and liver weight, and controlled aspartate aminotransferase (ALT), aspartate transaminase (AST), triglyceride (TG), urea nitrogen (BUN), and uric acid (UA) levels in the blood, which are features of NAFLD. Further, treatment with MJM60958 also reduced steatosis scores in liver tissues, serum leptin and interleukin, and increased serum adiponectin content. Moreover, administration of MJM60958 resulted in a significantly decreased expression of some genes and proteins which are related to lipid accumulation, such as fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and sterol regulatory element-binding protein 1 (SREBP-1), and also upregulated genes and protein expression of lipid oxidation such as peroxisome proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase 1a (CPT1A). Administration of MJM60958 increased the relative abundance of specific microbial taxa such as Verrucomicrobia, which are abundant in non-NAFLD mice, and reduced Firmicutes, which are a major group in NAFLD mice. MJM60958 affected the modulation of gut microbiota and altered the strain profile of short-chain fatty acids (SCFAs) production in the cecum by reduced lactic acid and enhanced acetic acid production. Overall, MJM60958 showed potential as a probiotic that can prevent and treat NAFLD.
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27
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Kuraji R, Kapila Y, Numabe Y. Periodontal Disease and Nonalcoholic Fatty Liver Disease: New Microbiome-Targeted Therapy Based on the Oral–Gut–Liver Axis Concept. CURRENT ORAL HEALTH REPORTS 2022; 9:89-102. [DOI: 10.1007/s40496-022-00312-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 04/26/2022] [Indexed: 01/03/2025]
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28
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Davachi SM, Dogan B, Khazdooz L, Zhang S, Khojastegi A, Fei Z, Sun H, Meletharayil G, Kapoor R, Simpson KW, Abbaspourrad A. Long-Term Lacticaseibacillus rhamnosus GG Storage at Ambient Temperature in Vegetable Oil: Viability and Functional Assessments. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022; 70:9399-9411. [PMID: 35881537 DOI: 10.1021/acs.jafc.2c02953] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Vegetable oils with varying saturated fat levels were inoculated with Lacticaseibacillus rhamnosus GG (LGG), subjected to different heat treatments in the absence and presence of inulin and stored for 12 months at room temperature. After storage, the heat-treated probiotics actively grew to high concentrations after removal of the oils and reculturing. The bacterial samples, regardless of aerobic or anaerobic conditions and treatment methods, showed no changes in their growth behavior. The random amplified polymorphic DNA-polymerase chain reaction, antimicrobial, morphology, and motility tests also showed no major differences. Samples of LGG treated with a higher antioxidant content (Gal400) showed reduced inflammatory and anti-inflammatory properties. These findings have been confirmed by metabolite and genome sequencing studies, indicating that Gal400 showed lower concentrations and secretion percentages and the highest number of single nucleotide polymorphisms. We have shown proof of concept that LGG can be stored in oil with minimum impact on probiotic in vitro viability.
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Affiliation(s)
- Seyed Mohammad Davachi
- Department of Food Science, College of Agriculture & Life Sciences, Cornell University, Stocking Hall, Ithaca, New York 14853, United States
| | - Belgin Dogan
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, United States
| | - Leila Khazdooz
- Department of Food Science, College of Agriculture & Life Sciences, Cornell University, Stocking Hall, Ithaca, New York 14853, United States
| | - Shiying Zhang
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, United States
| | - Anahita Khojastegi
- Department of Food Science, College of Agriculture & Life Sciences, Cornell University, Stocking Hall, Ithaca, New York 14853, United States
| | - Zhangjun Fei
- Boyce Thompson Institute, Cornell University, Ithaca, New York 14853, United States
| | - Honghe Sun
- Boyce Thompson Institute, Cornell University, Ithaca, New York 14853, United States
| | | | - Rohit Kapoor
- National Dairy Council, 10255 W Higgins Rd, Rosemont, Illinois 60018, United States
| | - Kenneth W Simpson
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, United States
| | - Alireza Abbaspourrad
- Department of Food Science, College of Agriculture & Life Sciences, Cornell University, Stocking Hall, Ithaca, New York 14853, United States
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29
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Hu W, Gao W, Liu Z, Fang Z, Wang H, Zhao J, Zhang H, Lu W, Chen W. Specific Strains of Faecalibacterium prausnitzii Ameliorate Nonalcoholic Fatty Liver Disease in Mice in Association with Gut Microbiota Regulation. Nutrients 2022; 14:nu14142945. [PMID: 35889903 PMCID: PMC9325077 DOI: 10.3390/nu14142945] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Revised: 07/13/2022] [Accepted: 07/13/2022] [Indexed: 12/04/2022] Open
Abstract
Evidence linking Faecalibacterium prausnitzii abundance to nonalcoholic fatty liver disease (NAFLD) is accumulating; however, the causal relationship remains obscure. In this study, 12 F. prausnitzii strains were orally administered to high fat diet fed C57BL/6J mice for 12 weeks to evaluate the protective effects of F. prausnitzii on NAFLD. We found that five F. prausnitzii strains, A2-165, LB8, ZF21, PL45, and LC49, significantly restored serum lipid profiles and ameliorated glucose intolerance, adipose tissue dysfunction, hepatic steatosis, inflammation, and oxidative stress in a mouse model of NAFLD. Moreover, two strains, LC49 and LB8, significantly enhanced short-chain fatty acid (SCFA) production and modulated the gut microbiota. Based on the combined analysis of linear discriminant analysis effect size and microbial communities, the core microbiome related to NAFLD comprised Odoribacter, Roseburia, Erysipelatoclostridium, Tyzzerella, Faecalibaculum, Blautia, and Acetatifactor, and the last five genera can be reversed by treatment with the LC49 and LB8 strains. Additionally, the LC49 and LB8 strains enriched Lactobacillus, Ileibacterium, Faecalibacterium, Dubosiella, and Bifidobacterium and downregulated pathways involving carbohydrate metabolism, amino acid metabolism, and fatty acid biosynthesis. Interestingly, LC49 supplementation also upregulated tryptophan metabolism, glutathione metabolism, and valine, leucine, and isoleucine degradation, which might be related to NAFLD prevention. Collectively, F. prausnitzii LC49 and LB8 exerted considerable anti-NAFLD and microbiota-regulating effects, indicating their potential as probiotic agents for NAFLD treatment.
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Affiliation(s)
- Wenbing Hu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (W.H.); (W.G.); (Z.L.); (Z.F.); (H.W.); (J.Z.); (H.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Wenyu Gao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (W.H.); (W.G.); (Z.L.); (Z.F.); (H.W.); (J.Z.); (H.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Zongmin Liu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (W.H.); (W.G.); (Z.L.); (Z.F.); (H.W.); (J.Z.); (H.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Zhifeng Fang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (W.H.); (W.G.); (Z.L.); (Z.F.); (H.W.); (J.Z.); (H.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Hongchao Wang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (W.H.); (W.G.); (Z.L.); (Z.F.); (H.W.); (J.Z.); (H.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Jianxin Zhao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (W.H.); (W.G.); (Z.L.); (Z.F.); (H.W.); (J.Z.); (H.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
| | - Hao Zhang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (W.H.); (W.G.); (Z.L.); (Z.F.); (H.W.); (J.Z.); (H.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
- (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China
- Wuxi Translational Medicine Research Center and Jiangsu Translational Medicine Research Institute Wuxi Branch, Wuxi 214122, China
| | - Wenwei Lu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (W.H.); (W.G.); (Z.L.); (Z.F.); (H.W.); (J.Z.); (H.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
- Correspondence: ; Tel./Fax: +86-510-8519-7302
| | - Wei Chen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (W.H.); (W.G.); (Z.L.); (Z.F.); (H.W.); (J.Z.); (H.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
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30
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Soundharrajan I, Karnan M, Jung JS, Lee KD, Lee JC, Ramesh T, Kim D, Choi KC. A Transcriptomic Response to Lactiplantibacillus plantarum-KCC48 against High-Fat Diet-Induced Fatty Liver Diseases in Mice. Int J Mol Sci 2022; 23:6750. [PMID: 35743193 PMCID: PMC9224190 DOI: 10.3390/ijms23126750] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Revised: 06/15/2022] [Accepted: 06/15/2022] [Indexed: 02/05/2023] Open
Abstract
The most prevalent chronic liver disorder in the world is fatty liver disease caused by a high-fat diet. We examined the effects of Lactiplantibacillus plantarum-KCC48 on high-fat diet-induced (HFD) fatty liver disease in mice. We used the transcriptome tool to perform a systematic evaluation of hepatic mRNA transcripts changes in high-fat diet (HFD)-fed animals and high-fat diet with L. plantarum (HFLPD)-fed animals. HFD causes fatty liver diseases in animals, as evidenced by an increase in TG content in liver tissues compared to control animals. Based on transcriptome data, 145 differentially expressed genes (DEGs) were identified in the liver of HFD-fed mice compared to control mice. Moreover, 61 genes were differentially expressed in the liver of mice fed the HFLPD compared to mice fed the HFD. Additionally, 43 common DEGs were identified between HFD and HFLPD. These genes were enriched in metabolic processes, retinol metabolism, the PPAR signaling pathway, fatty acid degradation, arachidonic metabolism, and steroid hormone synthesis. Taking these data into consideration, it can be concluded that L. plantarum-KCC48 treatment significantly regulates the expression of genes involved in hepatosteatosis caused by HFD, which may prevent fatty liver disease.
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Affiliation(s)
- Ilavenil Soundharrajan
- Grassland and Forage Division, Rural Development Administration, National Institute of Animal Science, Cheonan 31000, Korea; (I.S.); (M.K.); (J.-S.J.)
| | - Muthusamy Karnan
- Grassland and Forage Division, Rural Development Administration, National Institute of Animal Science, Cheonan 31000, Korea; (I.S.); (M.K.); (J.-S.J.)
| | - Jeong-Sung Jung
- Grassland and Forage Division, Rural Development Administration, National Institute of Animal Science, Cheonan 31000, Korea; (I.S.); (M.K.); (J.-S.J.)
| | - Kyung-Dong Lee
- Department of Companion Animals, Dongsin University, Naju 58245, Korea;
| | - Jeong-Chae Lee
- Department of Bioactive Material Sciences and Research Center of Bioactive Materials, Jeonbuk National University, Jeonju 54896, Korea;
| | - Thiyagarajan Ramesh
- Department of Basic Medical Sciences, College of Medicine, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia;
| | - Dahye Kim
- Animal Genomics and Bioinformatics Division, National Institute of Animal Science, Wanju 55365, Korea
| | - Ki-Choon Choi
- Grassland and Forage Division, Rural Development Administration, National Institute of Animal Science, Cheonan 31000, Korea; (I.S.); (M.K.); (J.-S.J.)
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31
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Yang Y, Li M, Wang Q, Huang H, Zhao Y, Du F, Chen Y, Shen J, Luo H, Zhao Q, Zeng J, Li W, Chen M, Li X, Wang F, Sun Y, Gu L, Xiao Z, Wu X. Pueraria lobata starch regulates gut microbiota and alleviates high-fat high-cholesterol diet induced non-alcoholic fatty liver disease in mice. Food Res Int 2022; 157:111401. [DOI: 10.1016/j.foodres.2022.111401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 05/18/2022] [Accepted: 05/20/2022] [Indexed: 11/04/2022]
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Sabirin F, Lim SM, Neoh CF, Ramasamy K. Hepatoprotection of Probiotics Against Non-Alcoholic Fatty Liver Disease in vivo: A Systematic Review. Front Nutr 2022; 9:844374. [PMID: 35479741 PMCID: PMC9035816 DOI: 10.3389/fnut.2022.844374] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Accepted: 03/03/2022] [Indexed: 12/20/2022] Open
Abstract
Probiotic supplements have been increasingly reported for their usefulness in delaying the development and progression of non-alcoholic fatty liver disease (NAFLD). Literature on the impact of probiotics on NAFLD covered various aspects of the disease. This study was undertaken to systematically review in vivo findings on hepatoprotection of probiotics against NAFLD. The literature search was performed through Cochrane, PubMed/MEDLINE, Embase, and Web of Science databases. Interventions of known probiotics in NAFLD-induced animal model with at least one measurable NAFLD-related parameter were included. The data were extracted by all authors independently. Quality assessment was conducted using the Systematic Review Center for Laboratory animal Experimentation (SYRCLE's) Risk of Bias (RoB) tool. P-values of measures were compared inter- and intra-study for each parameter. Forty-four probiotic-based studies of NAFLD-induced rodents were shortlisted. The majority of the studies were presented with low/unclear risk of bias. Probiotics improved the histopathology of NAFLD rodents (primary outcome). Most of the probiotic-supplemented NAFLD rodents were presented with mixed effects on serum liver enzymes but with improved hepatic and serum lipid profiles (including increased serum high-density lipoprotein cholesterol). The findings were generally accompanied by downregulation of hepatic lipogenic, oxidative, and inflammatory signallings. Probiotics were found to modulate gut microbiota composition and its products, and intestinal permeability. Probiotics also resulted in better glycaemic control and reduced liver weight. Altogether, the present qualitative appraisals strongly implied the hepatoprotective potential of probiotics against NAFLD in vivo.
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Affiliation(s)
- Faezah Sabirin
- Collaborative Drug Discovery Research (CDDR) Group, Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Cawangan Selangor, Kampus Puncak Alam, Bandar Puncak Alam, Malaysia
- Centre of Preclinical Science Studies, Faculty of Dentistry, Universiti Teknologi MARA (UiTM), Cawangan Selangor, Kampus Sungai Buloh, Sungai Buloh, Malaysia
| | - Siong Meng Lim
- Collaborative Drug Discovery Research (CDDR) Group, Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Cawangan Selangor, Kampus Puncak Alam, Bandar Puncak Alam, Malaysia
| | - Chin Fen Neoh
- Collaborative Drug Discovery Research (CDDR) Group, Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Cawangan Selangor, Kampus Puncak Alam, Bandar Puncak Alam, Malaysia
| | - Kalavathy Ramasamy
- Collaborative Drug Discovery Research (CDDR) Group, Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Cawangan Selangor, Kampus Puncak Alam, Bandar Puncak Alam, Malaysia
- *Correspondence: Kalavathy Ramasamy
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Tsai H, Wang Y, Liao C, Su C, Huang C, Chiu M, Yeh Y. Safety and the probiotic potential of
Bifidobacterium animalis
CP‐9. J Food Sci 2022; 87:2211-2228. [DOI: 10.1111/1750-3841.16129] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 01/30/2022] [Accepted: 02/28/2022] [Indexed: 12/01/2022]
Affiliation(s)
- Hui‐Yun Tsai
- Department of Nutrition and Health Science Fooyin University Kaohsiung Taiwan
- Aging and Disease Prevention Research Center Fooyin University Kaohsiung Taiwan
| | - Ya‐Chin Wang
- Department of Medical Laboratory Sciences and Biotechnology Fooyin University Kaohsiung Taiwan
| | - Chorng‐An Liao
- Aging and Disease Prevention Research Center Fooyin University Kaohsiung Taiwan
- Biomed Analysis Center Fooyin University Hospital Pingtung Taiwan
| | - Chia‐Yan Su
- Aging and Disease Prevention Research Center Fooyin University Kaohsiung Taiwan
- School of Pharmacy Kaohsiung Medical University Kaohsiung Taiwan
| | - Cheng‐Hsieh Huang
- Aging and Disease Prevention Research Center Fooyin University Kaohsiung Taiwan
- Ph. D. Program in Environmental and Occupational Medicine College of Medicine, Kaohsiung Medical University and National Health Research Institutes Kaohsiung Taiwan
| | - Min‐Hsi Chiu
- Aging and Disease Prevention Research Center Fooyin University Kaohsiung Taiwan
- Department of Medical Laboratory Sciences and Biotechnology Fooyin University Kaohsiung Taiwan
- Biomed Analysis Center Fooyin University Hospital Pingtung Taiwan
| | - Yao‐Tsung Yeh
- Aging and Disease Prevention Research Center Fooyin University Kaohsiung Taiwan
- Department of Medical Laboratory Sciences and Biotechnology Fooyin University Kaohsiung Taiwan
- Biomed Analysis Center Fooyin University Hospital Pingtung Taiwan
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Probiotic Strains Isolated from an Olympic Woman’s Weightlifting Gold Medalist Increase Weight Loss and Exercise Performance in a Mouse Model. Nutrients 2022; 14:nu14061270. [PMID: 35334927 PMCID: PMC8950690 DOI: 10.3390/nu14061270] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 03/10/2022] [Accepted: 03/15/2022] [Indexed: 02/01/2023] Open
Abstract
Obesity is a worldwide health problem. Calorie-restricted diets constitute a common intervention for treating obesity. However, an improper calorie-restricted diet can lead to malnutrition, fatigue, poor concretion, muscle loss, and reduced exercise performance. Probiotics have been introduced as an alternative treatment for obesity. In the present study, we tested the weight loss and exercise performance enhancement effectiveness of probiotic strains of different origins, including four isolated from an Olympic weightlifting gold medalist (Bifidobacterium longum subsp. longum OLP-01, Lactobacillus plantarum PL-02, Lactobacillus salivarius subsp. salicinius SA-03, and Lactococcus lactis subsp. lactis LY-66). A high-fat diet (HFD) was used to induce obesity in 16 groups of mice (n = 8/group). The mice were administered probiotic supplements at a dosage of 4.1 × 109 CFU/kg/day for 10 weeks. All probiotic supplementation groups showed a significant reduction in body weight and fat mass compared with the HFD group. TYCA06, CS-773, BLI-02, PL-02, bv-77, and OLP-01 were the most effective in facilitating weight loss and fat reduction, which may be due to fatty-acid absorbing activity. PL-02, LY-66, TYCA06, CS-773, and OLP-01 elevated the animals’ grip strength and exhaustive running duration. PL-02, LY-66, and OLP-01 increased tissue glycogen (liver and muscle) levels and muscle capillary density and reduced blood lactate production levels after exercise. In conclusion, OLP-01, PL-02, LY-66, TYCA06, and CS-773 were highly effective in enhancing weight loss and exercise performance. This study should be repeated on humans in the future to further confirm the findings.
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Wang S, Ren H, Zhong H, Zhao X, Li C, Ma J, Gu X, Xue Y, Huang S, Yang J, Chen L, Chen G, Qu S, Liang J, Qin L, Huang Q, Peng Y, Li Q, Wang X, Zou Y, Shi Z, Li X, Li T, Yang H, Lai S, Xu G, Li J, Zhang Y, Gu Y, Wang W. Combined berberine and probiotic treatment as an effective regimen for improving postprandial hyperlipidemia in type 2 diabetes patients: a double blinded placebo controlled randomized study. Gut Microbes 2022; 14:2003176. [PMID: 34923903 PMCID: PMC8726654 DOI: 10.1080/19490976.2021.2003176] [Citation(s) in RCA: 46] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Non-fasting lipidemia (nFL), mainly contributed by postprandial lipidemia (PL), has recently been recognized as an important cardiovascular disease (CVD) risk as fasting lipidemia (FL). PL serves as a common feature of dyslipidemia in Type 2 Diabetes (T2D), albeit effective therapies targeting on PL were limited. In this study, we aimed to evaluate whether the therapy combining probiotics (Prob) and berberine (BBR), a proven antidiabetic and hypolipidemic regimen via altering gut microbiome, could effectively reduce PL in T2D and to explore the underlying mechanism. Blood PL (120 min after taking 100 g standard carbohydrate meal) was examined in 365 participants with T2D from the Probiotics and BBR on the Efficacy and Change of Gut Microbiota in Patients with Newly Diagnosed Type 2 Diabetes (PREMOTE study), a random, placebo-controlled, and multicenter clinical trial. Prob+BBR was superior to BBR or Prob alone in improving postprandial total cholesterol (pTC) and low-density lipoprotein cholesterol (pLDLc) levels with decrement of multiple species of postprandial lipidomic metabolites after 3 months follow-up. This effect was linked to the changes of fecal Bifidobacterium breve level responding to BBR alone or Prob+BBR treatment. Four fadD genes encoding long-chain acyl-CoA synthetase were identified in the genome of this B. breve strain, and transcriptionally activated by BBR. In vitro BBR treatment further decreased the concentration of FFA in the culture medium of B. breve compared to vehicle. Thus, the activation of fadD by BBR could enhance FFA import and mobilization in B. breve and diliminish the intraluminal lipids for absorption to mediate the effect of Prob+BBR on PL. Our study confirmed that BBR and Prob (B. breve) could exert a synergistic hypolipidemic effect on PL, acting as a gut lipid sink to achieve better lipidemia and CVD risk control in T2D.
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Affiliation(s)
- Shujie Wang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China,Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the Pr China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Huahui Ren
- BGI-Shenzhen, Shenzhen, China,Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark
| | | | - Xinjie Zhao
- Dalian Institute of Chemical Physics, Chinese Academy of Science, Dalian, China
| | - Changkun Li
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China,Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the Pr China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China,Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jing Ma
- Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xuejiang Gu
- Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Province, China
| | - Yaoming Xue
- Nanfang Hospital, Southern Medical University, Guangdong Province, China
| | - Shan Huang
- Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jialin Yang
- Department of Endocrinology, Central Hospital of Minhang District, Shanghai, China
| | - Li Chen
- Department of Endocrinology, Qilu Hospital of Shandong University, Shandong Province, China
| | - Gang Chen
- Department of Endocrinology, Fujian Provincial Hospital, Fujian Province, China
| | - Shen Qu
- Department of Endocrinology, Shanghai Tenth People’s Hospital of Tong Ji University, Shanghai, China
| | - Jun Liang
- Department of Endocrinology, Xuzhou Central Hospital, Jiangsu Province, China
| | - Li Qin
- Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qin Huang
- Chang Hai Hospital, Second Military Medical University, Shanghai, China
| | - Yongde Peng
- Shanghai First People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qi Li
- Dalian Institute of Chemical Physics, Chinese Academy of Science, Dalian, China
| | - Xiaolin Wang
- Dalian Institute of Chemical Physics, Chinese Academy of Science, Dalian, China
| | | | | | - Xuelin Li
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China,Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the Pr China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tingting Li
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China,Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the Pr China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Huanming Yang
- BGI-Shenzhen, Shenzhen, China,James D. Watson Institute of Genome Sciences, Hangzhou, China
| | - Shenghan Lai
- Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Guowang Xu
- Dalian Institute of Chemical Physics, Chinese Academy of Science, Dalian, China
| | - Junhua Li
- BGI-Shenzhen, Shenzhen, China,CONTACT Junhua Li BGI-Shenzhen, Shenzhen, China
| | - Yifei Zhang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China,Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the Pr China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China,Yifei Zhang Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yanyun Gu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China,Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the Pr China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China,Yanyun Gu Shanghai National Clinical Research Center for metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China
| | - Weiqing Wang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China,Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the Pr China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China,Weiqing Wang, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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36
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Gut Microbiome in Non-Alcoholic Fatty Liver Disease: From Mechanisms to Therapeutic Role. Biomedicines 2022; 10:biomedicines10030550. [PMID: 35327352 PMCID: PMC8945462 DOI: 10.3390/biomedicines10030550] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 02/16/2022] [Accepted: 02/17/2022] [Indexed: 12/11/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is considered to be a significant health threat globally, and has attracted growing concern in the research field of liver diseases. NAFLD comprises multifarious fatty degenerative disorders in the liver, including simple steatosis, steatohepatitis and fibrosis. The fundamental pathophysiology of NAFLD is complex and multifactor-driven. In addition to viruses, metabolic syndrome and alcohol, evidence has recently indicated that the microbiome is related to the development and progression of NAFLD. In this review, we summarize the possible microbiota-based therapeutic approaches and highlight the importance of establishing the diagnosis of NAFLD through the different spectra of the disease via the gut–liver axis.
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Liao CA, Huang CH, Ho HH, Chen JF, Kuo YW, Lin JH, Tsai SY, Tsai HY, Yeh YT. A Combined Supplement of Probiotic Strains AP-32, bv-77, and CP-9 Increased Akkermansia mucinphila and Reduced Non-Esterified Fatty Acids and Energy Metabolism in HFD-Induced Obese Rats. Nutrients 2022; 14:nu14030527. [PMID: 35276886 PMCID: PMC8839477 DOI: 10.3390/nu14030527] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 01/17/2022] [Accepted: 01/18/2022] [Indexed: 02/07/2023] Open
Abstract
Obesity is referred to as a condition in which excess body fat has accumulated to an extent that it causes negative impacts on health. The formation of body fat is regulated by complicated networks in relation to energy metabolism, and gut microbiota have been regarded as a key player. Studies have shown that supplements of probiotics provide benefits to health, including an improvement in metabolic syndrome and the control of body weight. In the present study, three probiotic strains, AP-32, bv-77, and CP-9, stood out from nine candidates using a lipid consumption assay, and were subsequently introduced to further animal tests. A rodent model of obesity was induced by a high-fat diet (HFD) in Sprague-Dawley (SD) rats, and three probiotic strains were administered either separately or in a mixture. A low dose (5 × 109 CFU/kg/day) and a high dose (2.5 × 1010 CFU/kg/day) of probiotics were orally provided to obese rats. The bioeffects of the probiotic supplements were evaluated based on five aspects: (1) the body weight and growth rate; (2) ketone bodies, non-esterified fatty acids (NEFAs), and feed efficiency; (3) blood biochemistry; (4) fat content; and (5) gut microbiota composition. Our results demonstrated that the supplement of AP-32, CP-9, and bv-77 alleviated the increasing rate of body weight and prevented the elevation of NEFAs and ketone bodies in obese rats. Although the effect on fat content showed a minor improvement, the supplement of probiotics displayed significant improvements in HFD-induced poor blood biochemical characteristics, such as alanine aminotransferase (ALT), aspartate Transaminase (AST), and uric acid, within 4 weeks. Furthermore, the combined supplement of three strains significantly increased Akkermansia mucinphila as compared with three individual strains, while its enrichment was negatively correlated with NEFAs and energy metabolism. In general, a mixture of three probiotic strains delivered a better outcome than a single strain, and the high dose of supplements provided a more profound benefit than the low dose. In conclusion, three probiotic strains, AP-32, bv-77, and CP-9, can alleviate body fat formation in obese rats. Furthermore, a combined supplement of these three probiotic strains may have potential in treating or controlling metabolic disorders.
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Affiliation(s)
- Chorng-An Liao
- Aging and Diseases Prevention Research Center, Fooyin University, Kaohsiung 83102, Taiwan; (C.-A.L.); (C.-H.H.)
- Biomed Analysis Center, Fooyin Hospital, Pingtung 92847, Taiwan
| | - Cheng-Hsieh Huang
- Aging and Diseases Prevention Research Center, Fooyin University, Kaohsiung 83102, Taiwan; (C.-A.L.); (C.-H.H.)
- Ph.D. Program in Environmental and Occupational Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Hsieh-Hsun Ho
- Department of Research and Design, glac Biotech Co., Ltd., Tainan 74442, Taiwan; (H.-H.H.); (J.-F.C.); (Y.-W.K.); (J.-H.L.); (S.-Y.T.)
| | - Jui-Fen Chen
- Department of Research and Design, glac Biotech Co., Ltd., Tainan 74442, Taiwan; (H.-H.H.); (J.-F.C.); (Y.-W.K.); (J.-H.L.); (S.-Y.T.)
| | - Yi-Wei Kuo
- Department of Research and Design, glac Biotech Co., Ltd., Tainan 74442, Taiwan; (H.-H.H.); (J.-F.C.); (Y.-W.K.); (J.-H.L.); (S.-Y.T.)
| | - Jia-Hung Lin
- Department of Research and Design, glac Biotech Co., Ltd., Tainan 74442, Taiwan; (H.-H.H.); (J.-F.C.); (Y.-W.K.); (J.-H.L.); (S.-Y.T.)
| | - Shin-Yu Tsai
- Department of Research and Design, glac Biotech Co., Ltd., Tainan 74442, Taiwan; (H.-H.H.); (J.-F.C.); (Y.-W.K.); (J.-H.L.); (S.-Y.T.)
| | - Hui-Yun Tsai
- Aging and Diseases Prevention Research Center, Fooyin University, Kaohsiung 83102, Taiwan; (C.-A.L.); (C.-H.H.)
- Department of Nutrition and Health Science, Fooyin University, Kaohsiung 83102, Taiwan
- Correspondence: (H.-Y.T.); (Y.-T.Y.); Tel.: +886-7-781-1151 (ext. 6800) (H.-Y.T. & Y.-T.Y.)
| | - Yao-Tsung Yeh
- Aging and Diseases Prevention Research Center, Fooyin University, Kaohsiung 83102, Taiwan; (C.-A.L.); (C.-H.H.)
- Biomed Analysis Center, Fooyin Hospital, Pingtung 92847, Taiwan
- Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung 83102, Taiwan
- Correspondence: (H.-Y.T.); (Y.-T.Y.); Tel.: +886-7-781-1151 (ext. 6800) (H.-Y.T. & Y.-T.Y.)
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Dimet-Wiley A, Wu Q, Wiley JT, Eswar A, Neelakantan H, Savidge T, Watowich S. Reduced calorie diet combined with NNMT inhibition establishes a distinct microbiome in DIO mice. Sci Rep 2022; 12:484. [PMID: 35013352 PMCID: PMC8748953 DOI: 10.1038/s41598-021-03670-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Accepted: 12/01/2021] [Indexed: 11/29/2022] Open
Abstract
Treatment with a nicotinamide N-methyltransferase inhibitor (NNMTi; 5-amino-1-methylquinolinium) combined with low-fat diet (LD) promoted dramatic whole-body adiposity and weight loss in diet-induced obese (DIO) mice, rapidly normalizing these measures to age-matched lean animals, while LD switch alone was unable to restore these measures to age-matched controls in the same time frame. Since mouse microbiome profiles often highly correlate with body weight and fat composition, this study was designed to test whether the cecal microbiomes of DIO mice treated with NNMTi and LD were comparable to the microbiomes of age-matched lean counterparts and distinct from microbiomes of DIO mice maintained on a high-fat Western diet (WD) or subjected to LD switch alone. There were minimal microbiome differences between lean and obese controls, suggesting that diet composition and adiposity had limited effects. However, DIO mice switched from an obesity-promoting WD to an LD (regardless of treatment status) displayed several genera and phyla differences compared to obese and lean controls. While alpha diversity measures did not significantly differ between groups, beta diversity principal coordinates analyses suggested that mice from the same treatment group were the most similar. K-means clustering analysis of amplicon sequence variants by animal demonstrated that NNMTi-treated DIO mice switched to LD had a distinct microbiome pattern that was highlighted by decreased Erysipelatoclostridium and increased Lactobacillus relative abundances compared to vehicle counterparts; these genera are tied to body weight and metabolic regulation. Additionally, Parasutterella relative abundance, which was increased in both the vehicle- and NNMTi-treated LD-switched groups relative to the controls, significantly correlated with several adipose tissue metabolites' abundances. Collectively, these results provide a novel foundation for future investigations.
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Affiliation(s)
- Andrea Dimet-Wiley
- Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, USA
| | - Qinglong Wu
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA
| | - Jerrin T Wiley
- Depatment of Computer Science, University of Houston, Houston, TX, USA
| | - Aditya Eswar
- New York University Stern School of Business, New York City, NY, USA
| | | | - Tor Savidge
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA
| | - Stan Watowich
- Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, USA.
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Yang M, Zheng J, Zong X, Yang X, Zhang Y, Man C, Jiang Y. Preventive Effect and Molecular Mechanism of Lactobacillus rhamnosus JL1 on Food-Borne Obesity in Mice. Nutrients 2021; 13:3989. [PMID: 34836242 PMCID: PMC8621931 DOI: 10.3390/nu13113989] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 11/05/2021] [Accepted: 11/08/2021] [Indexed: 01/22/2023] Open
Abstract
Probiotics can prevent obesity and related metabolic complications. In our study, the protective effect and molecular mechanism of Lactobacillus rhamnosus JL1 (separated from the feces of healthy infants) on high-fat diet mice were investigated. After 10 weeks of dietary intervention with L. rhamnosus JL1 intervention, the body weight of the JL1 group (23.78 g) was significantly lower than that of the HFD group (26.59 g, p < 0.05) and the liver index was reduced. Serum biochemical analysis showed that the TC, TG and LDL-C contents of JL1 group mice were significantly decreased (p < 0.05). Histological images of the mice livers showed that the degree of lipid action and damage of hepatic cells were improved. L. rhamnosus JL1 activated the AMPK pathway, and reduced the gene expression of PPAR-γ, LXR-α and SREBP-1C. In addition, the protein expression of PPAR-γ and LXR-α were reduced. After dietary intervention with L. rhamnosus JL1, the concentration of acetic acid, propionic acid, and butyric acid were increased significantly, especially the concentration of butyric acid, which was 63.16% higher than that of the HFD group (p < 0.05). In conclusion, this study provided a theoretical reference for the development and application of probiotics derived from healthy infant feces in health products and functional foods.
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Affiliation(s)
| | | | | | | | | | | | - Yujun Jiang
- Key Laboratory of Dairy Science, Ministry of Education, Department of Food Science, Northeast Agricultural University, Harbin 150030, China; (M.Y.); (J.Z.); (X.Z.); (X.Y.); (Y.Z.); (C.M.)
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40
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Zhang FL, Yang YL, Zhang Z, Yao YY, Xia R, Gao CC, Du DD, Hu J, Ran C, Liu Z, Zhou ZG. Surface-Displayed Amuc_1100 From Akkermansia muciniphila on Lactococcus lactis ZHY1 Improves Hepatic Steatosis and Intestinal Health in High-Fat-Fed Zebrafish. Front Nutr 2021; 8:726108. [PMID: 34722607 PMCID: PMC8548614 DOI: 10.3389/fnut.2021.726108] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 09/07/2021] [Indexed: 01/14/2023] Open
Abstract
Fatty liver and intestinal barrier damage were widespread in most farmed fish, which severely restrict the development of aquaculture. Therefore, there was an urgent need to develop green feed additives to maintain host liver and intestinal health. In this study, a probiotic pili-like protein, Amuc_1100 (AM protein), was anchored to the surface of Lactococcus lactis ZHY1, and the effects of the recombinant bacteria AM-ZHY1 on liver fat accumulation and intestinal health were evaluated. Zebrafish were fed a basal diet, high-fat diet, and high-fat diet with AM-ZHY1 (108 cfu/g) or control bacteria ZHY1 for 4 weeks. Treatment with AM-ZHY1 significantly reduced hepatic steatosis in zebrafish. Quantitative PCR (qPCR) detection showed that the expression of the lipogenesis [peroxisome-proliferator-activated receptors (PPARγ), sterol regulatory element-binding proteins-1c (SREBP-1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase 1 (ACC1)] and lipid transport genes (CD36 and FABP6) in the liver were significantly downregulated (p < 0.05), indicating that AM-ZHY1 could reduce liver fat accumulation by inhibiting lipid synthesis and absorption. Moreover, supplementing AM-ZHY1 to a high-fat diet could significantly reduce serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, indicating that liver injury caused by high-fat diets was improved. The expression of tumor necrosis factor (TNF)-a and interleukin (IL)-6 in the liver decreased significantly (p < 0.05), while IL-1β and IL-10 did not change significantly in the AM-ZHY1 group. Compared to the high-fat diet-fed group, the AM-ZHY1 group, but not the ZHY1 group, significantly increased the expression of intestinal tight junction (TJ) proteins (TJP1a, claudina, claudin7, claudin7b, claudin11a, claudin12, and claudin15a; p < 0.05). Compared to the high-fat diet group, the Proteobacteria and Fusobacteria were significantly reduced and increased in the AM-ZHY1 group, respectively. In conclusion, the recombinant bacteria AM-ZHY1 has the capacity to maintain intestinal health by protecting intestinal integrity and improving intestinal flora structure and improving fatty liver disease by inhibiting lipid synthesis and absorption. This study will lay a foundation for the application of AM protein in improving abnormal fat deposition and restoring the intestinal barrier in fish.
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Affiliation(s)
- Feng-Li Zhang
- Sino-Norway Fish Gastrointestinal Microbiota Joint Lab, Institute of Feed Research of Chinese Academy of Agricultural Sciences, Beijing, China
| | - Ya-Lin Yang
- Key Laboratory for Feed Biotechnology of the Ministry of Agriculture, Institute of Feed Research of Chinese Academy of Agricultural Sciences, Beijing, China
| | - Zhen Zhang
- Key Laboratory for Feed Biotechnology of the Ministry of Agriculture, Institute of Feed Research of Chinese Academy of Agricultural Sciences, Beijing, China
| | - Yuan-Yuan Yao
- Sino-Norway Fish Gastrointestinal Microbiota Joint Lab, Institute of Feed Research of Chinese Academy of Agricultural Sciences, Beijing, China
| | - Rui Xia
- Sino-Norway Fish Gastrointestinal Microbiota Joint Lab, Institute of Feed Research of Chinese Academy of Agricultural Sciences, Beijing, China
| | - Chen-Chen Gao
- Sino-Norway Fish Gastrointestinal Microbiota Joint Lab, Institute of Feed Research of Chinese Academy of Agricultural Sciences, Beijing, China
| | - Dong-Dong Du
- Sino-Norway Fish Gastrointestinal Microbiota Joint Lab, Institute of Feed Research of Chinese Academy of Agricultural Sciences, Beijing, China
| | - Juan Hu
- Sino-Norway Fish Gastrointestinal Microbiota Joint Lab, Institute of Feed Research of Chinese Academy of Agricultural Sciences, Beijing, China
| | - Chao Ran
- Key Laboratory for Feed Biotechnology of the Ministry of Agriculture, Institute of Feed Research of Chinese Academy of Agricultural Sciences, Beijing, China
| | - Zhen Liu
- Hunan Provincial Key Laboratory of Nutrition and Quality Control of Aquatic Animals, Department of Biological and Environmental Engineering, Changsha University, Changsha, China
| | - Zhi-Gang Zhou
- Sino-Norway Fish Gastrointestinal Microbiota Joint Lab, Institute of Feed Research of Chinese Academy of Agricultural Sciences, Beijing, China
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Yamazaki K, Kato T, Tsuboi Y, Miyauchi E, Suda W, Sato K, Nakajima M, Yokoji-Takeuchi M, Yamada-Hara M, Tsuzuno T, Matsugishi A, Takahashi N, Tabeta K, Miura N, Okuda S, Kikuchi J, Ohno H, Yamazaki K. Oral Pathobiont-Induced Changes in Gut Microbiota Aggravate the Pathology of Nonalcoholic Fatty Liver Disease in Mice. Front Immunol 2021; 12:766170. [PMID: 34707622 PMCID: PMC8543001 DOI: 10.3389/fimmu.2021.766170] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2021] [Accepted: 09/28/2021] [Indexed: 12/12/2022] Open
Abstract
Background & Aims Periodontitis increases the risk of nonalcoholic fatty liver disease (NAFLD); however, the underlying mechanisms are unclear. Here, we show that gut dysbiosis induced by oral administration of Porphyromonas gingivalis, a representative periodontopathic bacterium, is involved in the aggravation of NAFLD pathology. Methods C57BL/6N mice were administered either vehicle, P. gingivalis, or Prevotella intermedia, another periodontopathic bacterium with weaker periodontal pathogenicity, followed by feeding on a choline-deficient, l-amino acid-defined, high-fat diet with 60 kcal% fat and 0.1% methionine (CDAHFD60). The gut microbial communities were analyzed by pyrosequencing the 16S ribosomal RNA genes. Metagenomic analysis was used to determine the relative abundance of the Kyoto Encyclopedia of Genes and Genomes pathways encoded in the gut microbiota. Serum metabolites were analyzed using nuclear magnetic resonance-based metabolomics coupled with multivariate statistical analyses. Hepatic gene expression profiles were analyzed via DNA microarray and quantitative polymerase chain reaction. Results CDAHFD60 feeding induced hepatic steatosis, and in combination with bacterial administration, it further aggravated NAFLD pathology, thereby increasing fibrosis. Gene expression analysis of liver samples revealed that genes involved in NAFLD pathology were perturbed, and the two bacteria induced distinct expression profiles. This might be due to quantitative and qualitative differences in the influx of bacterial products in the gut because the serum endotoxin levels, compositions of the gut microbiota, and serum metabolite profiles induced by the ingested P. intermedia and P. gingivalis were different. Conclusions Swallowed periodontopathic bacteria aggravate NAFLD pathology, likely due to dysregulation of gene expression by inducing gut dysbiosis and subsequent influx of gut bacteria and/or bacterial products.
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Affiliation(s)
- Kyoko Yamazaki
- Research Unit for Oral-Systemic Connection, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
- Division of Periodontology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Tamotsu Kato
- Laboratory for Intestinal Ecosystem, RIKEN Centre for Integrative Medical Sciences (IMS), Yokohama, Japan
| | - Yuuri Tsuboi
- RIKEN Center for Sustainable Resource Science, Yokohama, Japan
| | - Eiji Miyauchi
- Laboratory for Intestinal Ecosystem, RIKEN Centre for Integrative Medical Sciences (IMS), Yokohama, Japan
| | - Wataru Suda
- Laboratory for Microbiome Sciences, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
| | - Keisuke Sato
- Research Unit for Oral-Systemic Connection, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
- Division of Periodontology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Mayuka Nakajima
- Division of Periodontology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Mai Yokoji-Takeuchi
- Research Unit for Oral-Systemic Connection, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
- Division of Periodontology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Miki Yamada-Hara
- Research Unit for Oral-Systemic Connection, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
- Division of Periodontology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Takahiro Tsuzuno
- Research Unit for Oral-Systemic Connection, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
- Division of Periodontology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Aoi Matsugishi
- Research Unit for Oral-Systemic Connection, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
- Division of Periodontology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Naoki Takahashi
- Division of Periodontology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Koichi Tabeta
- Division of Periodontology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Nobuaki Miura
- Division of Bioinformatics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Shujiro Okuda
- Division of Bioinformatics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
- Medical AI Center, Niigata University School of Medicine, Niigata, Japan
| | - Jun Kikuchi
- RIKEN Center for Sustainable Resource Science, Yokohama, Japan
| | - Hiroshi Ohno
- Laboratory for Intestinal Ecosystem, RIKEN Centre for Integrative Medical Sciences (IMS), Yokohama, Japan
- Intestinal Microbiota Project, Kanagawa Institute of Industrial Science and Technology, Kawasaki, Japan
| | - Kazuhisa Yamazaki
- Research Unit for Oral-Systemic Connection, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
- Laboratory for Intestinal Ecosystem, RIKEN Centre for Integrative Medical Sciences (IMS), Yokohama, Japan
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Han H, Jiang Y, Wang M, Melaku M, Liu L, Zhao Y, Everaert N, Yi B, Zhang H. Intestinal dysbiosis in nonalcoholic fatty liver disease (NAFLD): focusing on the gut-liver axis. Crit Rev Food Sci Nutr 2021; 63:1689-1706. [PMID: 34404276 DOI: 10.1080/10408398.2021.1966738] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disorders in humans, partly because it is closely related to metabolic disorders of the liver with increasing prevalence. NAFLD begins with hepatic lipid accumulation, which may cause inflammation and eventually lead to fibrosis in the liver. Numerous studies have demonstrated the close relationship between gut dysfunction (especially the gut microbiota and its metabolites) and the occurrence and progression of NAFLD. The bidirectional communication between the gut and liver, named the gut-liver axis, is mainly mediated by the metabolites derived from both the liver and gut through the biliary tract, portal vein, and systemic circulation. Herein, we review the effects of the gut-liver axis on the pathogenesis of NAFLD. We also comprehensively describe the potential molecular mechanisms from the perspective of the role of liver-derived metabolites and gut-related components in hepatic metabolism and inflammation and gut health, respectively. The study provides insights into the mechanisms underlying current summarizations that support the intricate interactions between a disordered gut and NAFLD and can provide novel strategies to lessen the prevalence and consequence of NAFLD.
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Affiliation(s)
- Hui Han
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.,Precision Livestock and Nutrition Unit, Gembloux Agro-Bio Tech, University of Liège, Gembloux, Belgium
| | - Yi Jiang
- Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Hubei, China
| | - Mengyu Wang
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Mebratu Melaku
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.,Department of Animal Production and Technology, College of Agriculture, Woldia University, Woldia, Ethiopia
| | - Lei Liu
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Yong Zhao
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Nadia Everaert
- Precision Livestock and Nutrition Unit, Gembloux Agro-Bio Tech, University of Liège, Gembloux, Belgium
| | - Bao Yi
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Hongfu Zhang
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China
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Kim SJ, Choi SI, Jang M, Jeong YA, Kang CH, Kim GH. Combination of Limosilactobacillus fermentum MG4231 and MG4244 attenuates lipid accumulation in high-fat diet-fed obese mice. Benef Microbes 2021; 12:479-491. [PMID: 34348593 DOI: 10.3920/bm2020.0205] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
We investigated the anti-obesity effect and the underlying mechanisms of action of human-derived Limosilactobacillus fermentum MG4231, MG4244, and their combination, in high-fat diet-induced obese mice. Administration of the Limosilactobacillus strains decreased body weight gain, liver and adipose tissue weight, and glucose tolerance. Serum levels of total cholesterol, low-density lipoprotein-cholesterol, and leptin were reduced, while adiponectin increased. The administration of Limosilactobacillus strains improved the histopathological features of liver tissue, such as hepatic atrophy and inflammatory penetration, and significantly reduced the content of triglyceride in the liver. Limosilactobacillus administration discovered a significant reduction in the size of the adipocytes in the epididymal tissue. Limosilactobacillus treatment significantly reduced the expression of important regulators in lipid metabolism, including peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein α, fatty acid synthase (FAS), adipocyte-protein 2, and lipoprotein lipase in the epididymal tissue. Also, Limosilactobacillus lowered sterol regulatory element-binding protein 1-c and FAS in the liver tissue. Such changes in the expression of these regulators in both liver and epididymis tissue were caused by Limosilactobacillus upregulating phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase. Therefore, we suggest that the use of the combination of L. fermentum MG4231 and MG4244, as probiotics could effectively inhibit adipogenesis and lipogenesis from preventing obesity.
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Affiliation(s)
- S J Kim
- Department of Health Functional Materials, Duksung Women's University, 144 gil, Dobong-gu, Seoul, 01369, Republic of Korea
| | - S-I Choi
- Department of Health Functional Materials, Duksung Women's University, 144 gil, Dobong-gu, Seoul, 01369, Republic of Korea
| | - M Jang
- Department of Food and Life Science, Inje University, Gimhae, Republic of Korea
| | - Y-A Jeong
- R&D Center, MEDIOGEN Co., Ltd., Seoul, Republic of Korea
| | - C-H Kang
- R&D Center, MEDIOGEN Co., Ltd., Seoul, Republic of Korea
| | - G-H Kim
- Department of Food and Nutrition, Duksung Women's University, 33, Samyang-ro 144-gil, Dobong-gu, Seoul, 01369, Republic of Korea
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Probiotics and Prebiotics as a Strategy for Non-Alcoholic Fatty Liver Disease, a Narrative Review. Foods 2021; 10:foods10081719. [PMID: 34441497 PMCID: PMC8394424 DOI: 10.3390/foods10081719] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 07/15/2021] [Accepted: 07/16/2021] [Indexed: 12/17/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a chronic non-communicable disease, with a prevalence of 25% worldwide. This pathology is a multifactorial illness, and is associated with different risks factors, including hypertension, hyperglycemia, dyslipidemia, and obesity. Beside these predisposing features, NAFLD has been related to changes in the microbiota, which favor the disease progression. In this context, the modulation of the gut microbiota has emerged as a new therapeutic target for the prophylaxis and treatment of NAFLD. This review describes the changes in the gut microbiota associated with NAFLD and the effect of probiotics, prebiotics, and synbiotics on the gut microbiota, liver damage, anthropometric parameters, blood lipids, inflammation markers and insulin resistance in these patients.
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Tokuhara D. Role of the Gut Microbiota in Regulating Non-alcoholic Fatty Liver Disease in Children and Adolescents. Front Nutr 2021; 8:700058. [PMID: 34250000 PMCID: PMC8267179 DOI: 10.3389/fnut.2021.700058] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Accepted: 06/04/2021] [Indexed: 01/18/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in children and adolescents. Although obesity is the leading cause of NAFLD, the etiologies of NAFLD are multifactorial (e.g., high-fat diet, a lack of exercise, gender, maternal obesity, the antibiotic use), and each of these factors leads to dysbiosis of the gut microbiota community. The gut microbiota is a key player in the development and regulation of the gut mucosal immune system as well as the regulation of both NAFLD and obesity. Dysbiosis of the gut microbiota promotes the development of NAFLD via alteration of gut-liver homeostasis, including disruption of the gut barrier, portal transport of bacterial endotoxin (lipopolysaccharide) to the liver, altered bile acid profiles, and decreased concentrations of short-chain fatty acids. In terms of prevention and treatment, conventional approaches (e.g., dietary and exercise interventions) against obesity and NAFLD have been confirmed to recover the dysbiosis and dysbiosis-mediated altered metabolism. In addition, increased understanding of the importance of gut microbiota-mediated homeostasis in the prevention of NAFLD suggests the potential effectiveness of gut microbiota-targeted preventive and therapeutic strategies (e.g., probiotics and fecal transplantation) against NAFLD in children and adolescents. This review comprehensively summarizes our current knowledge of the gut microbiota, focusing on its interaction with NAFLD and its potential therapeutic role in obese children and adolescents with this disorder.
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Affiliation(s)
- Daisuke Tokuhara
- Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka, Japan
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46
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Khan A, Ding Z, Ishaq M, Bacha AS, Khan I, Hanif A, Li W, Guo X. Understanding the Effects of Gut Microbiota Dysbiosis on Nonalcoholic Fatty Liver Disease and the Possible Probiotics Role: Recent Updates. Int J Biol Sci 2021; 17:818-833. [PMID: 33767591 PMCID: PMC7975705 DOI: 10.7150/ijbs.56214] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 12/24/2020] [Indexed: 02/07/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is leading chronic liver syndrome worldwide. Gut microbiota dysbiosis significantly contributes to the pathogenesis and severity of NAFLD. However, its role is complex and even unclear. Treatment of NAFLD through chemotherapeutic agents have been questioned because of their side effects on health. In this review, we highlighted and discussed the current understanding on the importance of gut microbiota, its dysbiosis and its effects on the gut-liver axis and gut mucosa. Further, we discussed key mechanisms involved in gut dysbiosis to provide an outline of its role in progression to NAFLD and liver cirrhosis. In addition, we also explored the potential role of probiotics as a treatment approach for the prevention and treatment of NAFLD. Based on the latest findings, it is evident that microbiota targeted interventions mostly the use of probiotics have shown promising effects and can possibly alleviate the gut microbiota dysbiosis, regulate the metabolic pathways which in turn inhibit the progression of NAFLD through the gut-liver axis. However, very limited studies in humans are available on this issue and suggest further research work to identify a specific core microbiome association with NAFLD and to discover its mechanism of pathogenesis, which will help to enhance the therapeutic potential of probiotics to NAFLD.
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Affiliation(s)
- Ashiq Khan
- School of Life Sciences, Probiotics and Biological Feed Research Centre, Lanzhou University, Lanzhou 730000, PR China
- Department of Microbiology, Balochistan University of Information Technology Engineering & Management Sciences Quetta 87300, Pakistan
| | - Zitong Ding
- School of Life Sciences, Probiotics and Biological Feed Research Centre, Lanzhou University, Lanzhou 730000, PR China
| | - Muhammad Ishaq
- School of Life Sciences, Probiotics and Biological Feed Research Centre, Lanzhou University, Lanzhou 730000, PR China
| | - Ali Sher Bacha
- School of Life Sciences, Probiotics and Biological Feed Research Centre, Lanzhou University, Lanzhou 730000, PR China
| | - Israr Khan
- School of Life Sciences, Institute of Microbiology Lanzhou University, Lanzhou 730000, PR China
| | - Anum Hanif
- School of Life Sciences, Probiotics and Biological Feed Research Centre, Lanzhou University, Lanzhou 730000, PR China
| | - Wenyuan Li
- School of Life Sciences, Probiotics and Biological Feed Research Centre, Lanzhou University, Lanzhou 730000, PR China
| | - Xusheng Guo
- School of Life Sciences, Probiotics and Biological Feed Research Centre, Lanzhou University, Lanzhou 730000, PR China
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Lamas-Paz A, Morán L, Peng J, Salinas B, López-Alcántara N, Sydor S, Vilchez-Vargas R, Asensio I, Hao F, Zheng K, Martín-Adrados B, Moreno L, Cogolludo A, Gómez del Moral M, Bechmann L, Martínez-Naves E, Vaquero J, Bañares R, Nevzorova YA, Cubero FJ. Intestinal Epithelial Cell-Derived Extracellular Vesicles Modulate Hepatic Injury via the Gut-Liver Axis During Acute Alcohol Injury. Front Pharmacol 2020; 11:603771. [PMID: 33408632 PMCID: PMC7779758 DOI: 10.3389/fphar.2020.603771] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Accepted: 10/05/2020] [Indexed: 12/12/2022] Open
Abstract
Binge drinking, i.e., heavy episodic drinking in a short time, has recently become an alarming societal problem with negative health impact. However, the harmful effects of acute alcohol injury in the gut-liver axis remain elusive. Hence, we focused on the physiological and pathological changes and the underlying mechanisms of experimental binge drinking in the context of the gut-liver axis. Eight-week-old mice with a C57BL/6 background received a single dose (p.o.) of ethanol (EtOH) [6 g/kg b.w.] as a preclinical model of acute alcohol injury. Controls received a single dose of PBS. Mice were sacrificed 8 h later. In parallel, HepaRGs and Caco-2 cells, human cell lines of differentiated hepatocytes and intestinal epithelial cells intestinal epithelial cells (IECs), respectively, were challenged in the presence or absence of EtOH [0-100 mM]. Extracellular vesicles (EVs) isolated by ultracentrifugation from culture media of IECs were added to hepatocyte cell cultures. Increased intestinal permeability, loss of zonula occludens-1 (ZO-1) and MUCIN-2 expression, and alterations in microbiota-increased Lactobacillus and decreased Lachnospiraceae species-were found in the large intestine of mice exposed to EtOH. Increased TUNEL-positive cells, infiltration of CD11b-positive immune cells, pro-inflammatory cytokines (e.g., tlr4, tnf, il1β), and markers of lipid accumulation (Oil Red O, srbep1) were evident in livers of mice exposed to EtOH, particularly in females. In vitro experiments indicated that EVs released by IECs in response to ethanol exerted a deleterious effect on hepatocyte viability and lipid accumulation. Overall, our data identified a novel mechanism responsible for driving hepatic injury in the gut-liver axis, opening novel avenues for therapy.
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Affiliation(s)
- Arantza Lamas-Paz
- Department of Immunology, Ophthalmology and ENT, Complutense University School of Medicine, Madrid, Spain
- 12 de Octubre Health Research Institute (imas12), Madrid, Spain
| | - Laura Morán
- Department of Immunology, Ophthalmology and ENT, Complutense University School of Medicine, Madrid, Spain
- Servicio de Aparato Digestivo del Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Jin Peng
- Department of Hepatobiliary Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Beatriz Salinas
- Servicio de Aparato Digestivo del Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
- Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain
- Bioengineering and Aerospace Engineering Department, Universidad Carlos III de Madrid, Madrid, Spain
- Centro de Investigación Biomédico en Red de Salud Mental (CIBERSAM), Madrid, Spain
| | - Nuria López-Alcántara
- Department of Immunology, Ophthalmology and ENT, Complutense University School of Medicine, Madrid, Spain
| | - Svenja Sydor
- Department of Internal Medicine, University Hospital Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany
| | - Ramiro Vilchez-Vargas
- Department of Gastroenterology, Hepatology, and Infectious Diseases, Otto von Guericke University Hospital Magdeburg, Magdeburg, Germany
| | - Iris Asensio
- Servicio de Aparato Digestivo del Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
- Centre for Biomedical Research, Network on Liver and Digestive Diseases (CIBEREHD), Madrid, Spain
| | - Fengjie Hao
- Department of Immunology, Ophthalmology and ENT, Complutense University School of Medicine, Madrid, Spain
- 12 de Octubre Health Research Institute (imas12), Madrid, Spain
- Department of General Surgery, Hepatobiliary Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Kang Zheng
- Department of Immunology, Ophthalmology and ENT, Complutense University School of Medicine, Madrid, Spain
- 12 de Octubre Health Research Institute (imas12), Madrid, Spain
- Department of Anesthesiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Beatriz Martín-Adrados
- Department of Immunology, Ophthalmology and ENT, Complutense University School of Medicine, Madrid, Spain
- 12 de Octubre Health Research Institute (imas12), Madrid, Spain
| | - Laura Moreno
- Department of Internal Medicine, University Hospital Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany
- Department of Pharmacology and Toxicology, Complutense University School of Medicine and Centre for Biomedical Research, Network on Respiratory Diseases (CIBERES), Madrid, Spain
| | - Angel Cogolludo
- Department of Internal Medicine, University Hospital Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany
- Department of Pharmacology and Toxicology, Complutense University School of Medicine and Centre for Biomedical Research, Network on Respiratory Diseases (CIBERES), Madrid, Spain
| | - Manuel Gómez del Moral
- 12 de Octubre Health Research Institute (imas12), Madrid, Spain
- Department of Cell Biology, Complutense University School of Medicine, Madrid, Spain
| | - Lars Bechmann
- Department of Internal Medicine, University Hospital Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany
| | - Eduardo Martínez-Naves
- Department of Immunology, Ophthalmology and ENT, Complutense University School of Medicine, Madrid, Spain
- 12 de Octubre Health Research Institute (imas12), Madrid, Spain
| | - Javier Vaquero
- Servicio de Aparato Digestivo del Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
- Centre for Biomedical Research, Network on Liver and Digestive Diseases (CIBEREHD), Madrid, Spain
| | - Rafael Bañares
- Servicio de Aparato Digestivo del Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
- Centre for Biomedical Research, Network on Liver and Digestive Diseases (CIBEREHD), Madrid, Spain
| | - Yulia A. Nevzorova
- Department of Immunology, Ophthalmology and ENT, Complutense University School of Medicine, Madrid, Spain
- 12 de Octubre Health Research Institute (imas12), Madrid, Spain
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany
| | - Francisco Javier Cubero
- Department of Immunology, Ophthalmology and ENT, Complutense University School of Medicine, Madrid, Spain
- 12 de Octubre Health Research Institute (imas12), Madrid, Spain
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Rives C, Fougerat A, Ellero-Simatos S, Loiseau N, Guillou H, Gamet-Payrastre L, Wahli W. Oxidative Stress in NAFLD: Role of Nutrients and Food Contaminants. Biomolecules 2020; 10:E1702. [PMID: 33371482 PMCID: PMC7767499 DOI: 10.3390/biom10121702] [Citation(s) in RCA: 85] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 12/14/2020] [Accepted: 12/15/2020] [Indexed: 12/14/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is often the hepatic expression of metabolic syndrome and its comorbidities that comprise, among others, obesity and insulin-resistance. NAFLD involves a large spectrum of clinical conditions. These range from steatosis, a benign liver disorder characterized by the accumulation of fat in hepatocytes, to non-alcoholic steatohepatitis (NASH), which is characterized by inflammation, hepatocyte damage, and liver fibrosis. NASH can further progress to cirrhosis and hepatocellular carcinoma. The etiology of NAFLD involves both genetic and environmental factors, including an unhealthy lifestyle. Of note, unhealthy eating is clearly associated with NAFLD development and progression to NASH. Both macronutrients (sugars, lipids, proteins) and micronutrients (vitamins, phytoingredients, antioxidants) affect NAFLD pathogenesis. Furthermore, some evidence indicates disruption of metabolic homeostasis by food contaminants, some of which are risk factor candidates in NAFLD. At the molecular level, several models have been proposed for the pathogenesis of NAFLD. Most importantly, oxidative stress and mitochondrial damage have been reported to be causative in NAFLD initiation and progression. The aim of this review is to provide an overview of the contribution of nutrients and food contaminants, especially pesticides, to oxidative stress and how they may influence NAFLD pathogenesis.
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Affiliation(s)
- Clémence Rives
- Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRA, EVT, INP-Purpan, UPS, 31300 Toulouse, France; (C.R.); (A.F.); (S.E.-S.); (N.L.); (H.G.)
| | - Anne Fougerat
- Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRA, EVT, INP-Purpan, UPS, 31300 Toulouse, France; (C.R.); (A.F.); (S.E.-S.); (N.L.); (H.G.)
| | - Sandrine Ellero-Simatos
- Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRA, EVT, INP-Purpan, UPS, 31300 Toulouse, France; (C.R.); (A.F.); (S.E.-S.); (N.L.); (H.G.)
| | - Nicolas Loiseau
- Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRA, EVT, INP-Purpan, UPS, 31300 Toulouse, France; (C.R.); (A.F.); (S.E.-S.); (N.L.); (H.G.)
| | - Hervé Guillou
- Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRA, EVT, INP-Purpan, UPS, 31300 Toulouse, France; (C.R.); (A.F.); (S.E.-S.); (N.L.); (H.G.)
| | - Laurence Gamet-Payrastre
- Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRA, EVT, INP-Purpan, UPS, 31300 Toulouse, France; (C.R.); (A.F.); (S.E.-S.); (N.L.); (H.G.)
| | - Walter Wahli
- Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRA, EVT, INP-Purpan, UPS, 31300 Toulouse, France; (C.R.); (A.F.); (S.E.-S.); (N.L.); (H.G.)
- Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Clinical Sciences Building, 11 Mandalay Road, Singapore 308232, Singapore
- Center for Integrative Genomics, Université de Lausanne, Le Génopode, CH-1015 Lausanne, Switzerland
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García-Rodríguez A, Moreno-Olivas F, Marcos R, Tako E, Marques CNH, Mahler GJ. The Role of Metal Oxide Nanoparticles, Escherichia coli, and Lactobacillus rhamnosus on Small Intestinal Enzyme Activity. ENVIRONMENTAL SCIENCE. NANO 2020; 7:3940-3964. [PMID: 33815806 PMCID: PMC8011031 DOI: 10.1039/d0en01001d] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/04/2023]
Abstract
Engineered nanomaterials (ENMs) have become common in the food industry, which motivates the need to evaluate ENM effects on human health. Gastrointestinal (GI) in vitro models (e.g. Caco-2, Caco-2/HT29-MTX) have been used in nanotoxicology research. However, the human gut environment is composed of both human cells and the gut microbiota. The goal of this study is to increase the complexity of the Caco-2/HT29-MTX in vitro model by co-culturing human cells with the Gram-positive, commensal Lactobacillus rhamnosus or the Gram-negative, opportunistic Escherichia coli; with the hypothesis that the presence of bacteria would ameliorate the effects of exposure to metal oxide nanoparticles (NPs) such as iron oxide (Fe2O3), silicone dioxide (SiO2), titanium dioxide (TiO2), or zinc oxide (ZnO). To understand this relationship, Caco-2/HT29-MTX cell barriers were acutely co-exposed (4 hours) to bacteria and/or NPs (pristine or in vitro digested). The activity of the brush border membrane (BBM) enzymes intestinal alkaline phosphatase (IAP), aminopeptidase-N (APN), sucrase isomaltase (SI) and the basolateral membrane enzyme (BLM) Na+/K+ ATPase were assessed. Findings show that (i) the human digestion process alters the physicochemical properties of NPs, (ii) large agglomerates of NPs remain entrapped on the apical side of the intestinal barrier, which (iii) affects the activity of BBM enzymes. Interestingly, some NPs effects were attenuated in the presence of either bacterial strains. Confocal microscopy detected bacteria-NPs interactions, which may impede the NP-intestinal cell contact. These results highlight the importance of improving in vitro models to closely mimic the complexities of the human body.
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Affiliation(s)
- Alba García-Rodríguez
- Department of Biomedical Engineering, Binghamton University, Binghamton, NY, 13902, USA
- Binghamton Biofilm Research Center, Binghamton University, Binghamton, NY, 13902, USA
- Department of Biological Sciences, Binghamton University, Binghamton, NY, 1302, USA
- Department of Genetics and Microbiology, Faculty of Bioscience, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona, 08193, Spain
| | - Fabiola Moreno-Olivas
- Department of Biomedical Engineering, Binghamton University, Binghamton, NY, 13902, USA
- Binghamton Biofilm Research Center, Binghamton University, Binghamton, NY, 13902, USA
| | - Ricard Marcos
- Department of Genetics and Microbiology, Faculty of Bioscience, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona, 08193, Spain
| | - Elad Tako
- Department of Food Science, Cornell University, Stocking Hall, Ithaca, NY, 14853-7201, USA
| | - Cláudia N. H. Marques
- Binghamton Biofilm Research Center, Binghamton University, Binghamton, NY, 13902, USA
- Department of Biological Sciences, Binghamton University, Binghamton, NY, 1302, USA
| | - Gretchen J. Mahler
- Department of Biomedical Engineering, Binghamton University, Binghamton, NY, 13902, USA
- Binghamton Biofilm Research Center, Binghamton University, Binghamton, NY, 13902, USA
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50
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Huang E, Kim S, Park H, Park S, Ji Y, Todorov SD, Lim SD, Holzapfel WH. Modulation of the Gut Microbiome and Obesity Biomarkers by Lactobacillus Plantarum KC28 in a Diet-Induced Obesity Murine Model. Probiotics Antimicrob Proteins 2020; 13:677-697. [PMID: 33188637 DOI: 10.1007/s12602-020-09720-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/13/2020] [Indexed: 12/18/2022]
Abstract
Lactobacillus plantarum KC28 showed a beneficial (anti-obesity) effect in a diet-induced obese (DIO) C57BL/6 murine model receiving an intermediate high-fat diet (IF). This diet was selected for probiotic studies by prior comparisons of different combinations of basic (carbohydrate, protein and fat) components for optimized induction of dietary obesity in a murine model. Prior selection of Lact. plantarum strain KC28 was based on different physiological tests for safety and functionality including cell line adhesion and anti-adipogenic activity. The strain was administered at 5.0 × 109 CFU/mouse/day to the DIO mice (control mice received a normal diet). The anti-obesity effect of KC28 and the well-known probiotic strains Lact. rhamnosus GG (LGG) and Lact. plantarum 299v was assessed over 12 weeks. Xenical served as anti-obesity control. The high-fat diet groups receiving strains KC28 and LGG and the control Xenical group showed significant weight loss and notable changes in some obesity-related biomarkers in the liver (significant up-regulation of PGC1-α and CPT1-α only by KC28; p < 0.05) and mesenteric adipose tissue (significant down-regulation of ACOX-1, PPAR-γ, and FAS; KC28 p < 0.001 for PPAR-γ and FAS), compared with the IF control. Favourable changes in the studied biomarkers suggest a similar beneficial influence of Lact. plantarum KC28 on the alleviation of obesity comparable with that of the two well-studied probiotic strains, LGG and 299v. This probably resulted from a modulation in the cecal microbiota of the IF group by either probiotic strain, yet in a different manner, showing a highly significant increase in the families Desulfovibrionaceae and Lactobacillaceae only in the group receiving Lact. plantarum KC28.
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Affiliation(s)
- Eunchong Huang
- Department of Advanced Green Energy and Environment, Handong Global University, Pohang, Gyeongbuk, 37554, South Korea
| | - Seulki Kim
- Korea Food Research Institute, Wanju, 55365, South Korea
| | - Haryung Park
- Department of Advanced Green Energy and Environment, Handong Global University, Pohang, Gyeongbuk, 37554, South Korea.,Techno-Business Center, HEM Inc, Pohang, 37673, South Korea
| | - Soyoung Park
- Department of Advanced Green Energy and Environment, Handong Global University, Pohang, Gyeongbuk, 37554, South Korea.,Techno-Business Center, HEM Inc, Pohang, 37673, South Korea
| | - Yosep Ji
- Department of Advanced Green Energy and Environment, Handong Global University, Pohang, Gyeongbuk, 37554, South Korea.,Techno-Business Center, HEM Inc, Pohang, 37673, South Korea
| | - Svetoslav Dimitrov Todorov
- Department of Advanced Green Energy and Environment, Handong Global University, Pohang, Gyeongbuk, 37554, South Korea
| | - Sang-Dong Lim
- Korea Food Research Institute, Wanju, 55365, South Korea
| | - Wilhelm Heinrich Holzapfel
- Department of Advanced Green Energy and Environment, Handong Global University, Pohang, Gyeongbuk, 37554, South Korea. .,Techno-Business Center, HEM Inc, Pohang, 37673, South Korea.
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