The Complex Role of Gut Microbiota in Systemic Lupus Erythematosus and Lupus Nephritis: From Pathogenetic Factor to Therapeutic Target
The role of gut microbiota (GM) and intestinal dysbiosis in triggering the onset and/or modulating the severity and progression of lupus nephritis (LN) has been the object of intense research over the last few years. Some alterations at the phyla level, such as the abundance of Proteobacteria and re...
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MDPI AG
2025-02-01
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| author | Emanuele Parodi Marialuisa Novi Paolo Bottino Edoardo La Porta Guido Merlotti Luigi Mario Castello Franca Gotta Andrea Rocchetti Marco Quaglia |
| author_facet | Emanuele Parodi Marialuisa Novi Paolo Bottino Edoardo La Porta Guido Merlotti Luigi Mario Castello Franca Gotta Andrea Rocchetti Marco Quaglia |
| author_sort | Emanuele Parodi |
| collection | DOAJ |
| description | The role of gut microbiota (GM) and intestinal dysbiosis in triggering the onset and/or modulating the severity and progression of lupus nephritis (LN) has been the object of intense research over the last few years. Some alterations at the phyla level, such as the abundance of Proteobacteria and reduction in Firmicutes/Bacteroidetes (F/B) ratio and in α-diversity have been consistently reported in systemic lupus erythematosus (SLE), whereas a more specific role has been ascribed to some species (<i>Bacteroides thetaiotaomicron</i> and <i>Ruminococcus gnavus</i>) in LN. Underlying mechanisms include microbial translocation through a “leaky gut” and subsequent molecular mimicry, immune dysregulation (alteration of IFNγ levels and of balance between Treg and Th17 subsets), and epigenetic interactions. Levels of bacterial metabolites, such as butyrate and other short-chain fatty acids (SCFAs), appear to play a key role in modulating LN. Beyond bacterial components of GM, virome and mycobiome are also increasingly recognized as important players in the modulation of an immune response. On the other hand, microbiota-based therapy appears promising and includes diet, prebiotics, probiotics, symbiotics, and fecal microbiota transplantation (FMT). The modulation of microbiota could correct critical alterations, such as F/B ratio and Treg/Th17 imbalance, and blunt production of autoantibodies and renal damage. Despite current limits, GM is emerging as a powerful environmental factor that could be harnessed to interfere with key mechanisms leading to SLE, preventing flares and organ damage, including LN. The aim of this review is to provide a state-of-the-art analysis of the role of GM in triggering and modulating SLE and LN on the one hand, while exploring possible therapeutic manipulation of GM to control the disease on the other hand. |
| format | Article |
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| institution | OA Journals |
| issn | 2076-2607 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | MDPI AG |
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| series | Microorganisms |
| spelling | doaj-art-dd79f6e091464f4e826a9544de42abf32025-08-20T02:01:23ZengMDPI AGMicroorganisms2076-26072025-02-0113244510.3390/microorganisms13020445The Complex Role of Gut Microbiota in Systemic Lupus Erythematosus and Lupus Nephritis: From Pathogenetic Factor to Therapeutic TargetEmanuele Parodi0Marialuisa Novi1Paolo Bottino2Edoardo La Porta3Guido Merlotti4Luigi Mario Castello5Franca Gotta6Andrea Rocchetti7Marco Quaglia8Nephrology and Dialysis Unit, SS. Antonio e Biagio e Cesare Arrigo University Hospital, 15121 Alessandria, ItalyGastroenterology Unit, SS. Antonio e Biagio e Cesare Arrigo University Hospital, 15121 Alessandria, ItalyMicrobiology Unit, SS. Antonio e Biagio e Cesare Arrigo University Hospital, 15121 Alessandria, ItalyNephrology and Dialysis Unit, IRCCS Istituto Giannina Gaslini, 16147 Genoa, ItalyDepartment of Primary Care, Azienda Socio Sanitaria Territoriale (ASST) of Pavia, 27100 Pavia, ItalyInternal Medicine Unit, SS. Antonio e Biagio e Cesare Arrigo University Hospital, 15121 Alessandria, ItalyMicrobiology Unit, SS. Antonio e Biagio e Cesare Arrigo University Hospital, 15121 Alessandria, ItalyMicrobiology Unit, SS. Antonio e Biagio e Cesare Arrigo University Hospital, 15121 Alessandria, ItalyNephrology and Dialysis Unit, SS. Antonio e Biagio e Cesare Arrigo University Hospital, 15121 Alessandria, ItalyThe role of gut microbiota (GM) and intestinal dysbiosis in triggering the onset and/or modulating the severity and progression of lupus nephritis (LN) has been the object of intense research over the last few years. Some alterations at the phyla level, such as the abundance of Proteobacteria and reduction in Firmicutes/Bacteroidetes (F/B) ratio and in α-diversity have been consistently reported in systemic lupus erythematosus (SLE), whereas a more specific role has been ascribed to some species (<i>Bacteroides thetaiotaomicron</i> and <i>Ruminococcus gnavus</i>) in LN. Underlying mechanisms include microbial translocation through a “leaky gut” and subsequent molecular mimicry, immune dysregulation (alteration of IFNγ levels and of balance between Treg and Th17 subsets), and epigenetic interactions. Levels of bacterial metabolites, such as butyrate and other short-chain fatty acids (SCFAs), appear to play a key role in modulating LN. Beyond bacterial components of GM, virome and mycobiome are also increasingly recognized as important players in the modulation of an immune response. On the other hand, microbiota-based therapy appears promising and includes diet, prebiotics, probiotics, symbiotics, and fecal microbiota transplantation (FMT). The modulation of microbiota could correct critical alterations, such as F/B ratio and Treg/Th17 imbalance, and blunt production of autoantibodies and renal damage. Despite current limits, GM is emerging as a powerful environmental factor that could be harnessed to interfere with key mechanisms leading to SLE, preventing flares and organ damage, including LN. The aim of this review is to provide a state-of-the-art analysis of the role of GM in triggering and modulating SLE and LN on the one hand, while exploring possible therapeutic manipulation of GM to control the disease on the other hand.https://www.mdpi.com/2076-2607/13/2/445gut microbiotadysbiosisautoimmunitysystemic lupus erythematosuslupus nephritisprobiotic |
| spellingShingle | Emanuele Parodi Marialuisa Novi Paolo Bottino Edoardo La Porta Guido Merlotti Luigi Mario Castello Franca Gotta Andrea Rocchetti Marco Quaglia The Complex Role of Gut Microbiota in Systemic Lupus Erythematosus and Lupus Nephritis: From Pathogenetic Factor to Therapeutic Target Microorganisms gut microbiota dysbiosis autoimmunity systemic lupus erythematosus lupus nephritis probiotic |
| title | The Complex Role of Gut Microbiota in Systemic Lupus Erythematosus and Lupus Nephritis: From Pathogenetic Factor to Therapeutic Target |
| title_full | The Complex Role of Gut Microbiota in Systemic Lupus Erythematosus and Lupus Nephritis: From Pathogenetic Factor to Therapeutic Target |
| title_fullStr | The Complex Role of Gut Microbiota in Systemic Lupus Erythematosus and Lupus Nephritis: From Pathogenetic Factor to Therapeutic Target |
| title_full_unstemmed | The Complex Role of Gut Microbiota in Systemic Lupus Erythematosus and Lupus Nephritis: From Pathogenetic Factor to Therapeutic Target |
| title_short | The Complex Role of Gut Microbiota in Systemic Lupus Erythematosus and Lupus Nephritis: From Pathogenetic Factor to Therapeutic Target |
| title_sort | complex role of gut microbiota in systemic lupus erythematosus and lupus nephritis from pathogenetic factor to therapeutic target |
| topic | gut microbiota dysbiosis autoimmunity systemic lupus erythematosus lupus nephritis probiotic |
| url | https://www.mdpi.com/2076-2607/13/2/445 |
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