Gut Microbiota between Environment and Genetic Background in Familial Mediterranean Fever (FMF)

Ciaula, Agostino Di; Stella, Alessandro; Bonfrate, Leonilde; Wang, David Q.–H.; Portincasa, Piero

doi:10.3390/genes11091041

Cited by 18 publications

(14 citation statements)

References 188 publications

(254 reference statements)

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“…Studies have demonstrated that gut microbiota plays a certain role in the pathogenesis of febrile diseases, such as familial Mediterranean fever 23 and typhoid fever. 24 However, whether gut microbiota affects the presence of fever in COVID-19 patients is currently unknown.…”

Section: Discussionmentioning

confidence: 99%

Gut Microbiota Dysbiosis Correlates with Abnormal Immune Response in Moderate COVID-19 Patients with Fever

Zhou¹,

Shi²,

Fu³

et al. 2021

JIR

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Background Most COVID-19 patients are moderate, and fever is the most common clinical manifestation and associated with poorer prognosis. Gut microbiota may also play important roles in COVID-19 pathogenesis. However, the association between gut microbiota and fever in individuals with moderate COVID-19 remains unclear. Methods We compared the clinical features and laboratory results of 187 moderate COVID-19 patients with fever and without fever and identified several inflammatory markers in patients with fever. Then, we performed gut metagenome-wide association study for 31 individuals to identify the microbes and their epitopes which have potential role in fever and hyperinflammation. Results Among 187 moderate COVID-19 patients, 127 (67.9%) patients presented with fever. Lymphocytes, CD3+ T cells, CD4+ T cells and the ratio of CD4+ T cells to CD8+ T cells were significantly reduced, while AST, LDH, CRP, IL-6 and IL-10 were significantly elevated in patients with fever. Gut microbiome composition was significantly altered in patients with fever compared with those with non-fever. Opportunistic pathogens such as Enterococcus faecalis and Saccharomyces cerevisiae were enriched in patients with fever. E. faecalis was positively correlated with LDH and D-dimer and negatively correlated with CD8+T cells and IL-4, while S. cerevisiae was positively correlated with diarrhea symptom. Furthermore, several species with anti-inflammatory and protective effects, such as Bacteroides fragilis and Eubacterium ramulus , were enriched in patients with non-fever. B. fragilis was positively correlated with lymphocytes, and E. ramulus was negatively correlated with LDH, AST and IL-6. Finally, we found that several bacterial epitopes of GroEL, a homolog of human HSP60, were enriched in patients with fever and positively correlated with IL-6, IL-10, WBC, neutrophils, D-dimer, LDH, CRP, and E. faecalis . Conclusion Gut microbiota dysbiosis correlates with abnormal immune response in moderate COVID-19 patients with fever.

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Section: Discussionmentioning

confidence: 99%

Gut Microbiota Dysbiosis Correlates with Abnormal Immune Response in Moderate COVID-19 Patients with Fever

Zhou¹,

Shi²,

Fu³

et al. 2021

JIR

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“…The most well-studied example is the disorder familial Mediterranean fever (FMF), a genetic autoinflammatory disorder that causes recurrent fevers and painful inflammation in the abdomen, lungs, and joints. FMF is linked to a mutation in the human MEFV (Mediterranean fever) gene, which encodes the pyrin protein, a regulator of the innate immune system (Di Ciaula et al 2020). MEFV, through its innate immune function, also controls the gut microbiome composition (Di Ciaula et al 2020).…”

Section: Host Genetic Control Of the Microbiome Impacts Health And Diseasementioning

confidence: 99%

“…FMF is linked to a mutation in the human MEFV (Mediterranean fever) gene, which encodes the pyrin protein, a regulator of the innate immune system (Di Ciaula et al 2020). MEFV, through its innate immune function, also controls the gut microbiome composition (Di Ciaula et al 2020). During times of active FMF, the gut microbiome exhibits a depletion of total numbers of bacteria, loss of diversity, and shifts in relative abundance of populations of Bacteroidetes, Firmicutes, and Proteobacteria phyla (Khachatryan et al 2008).…”

Section: Host Genetic Control Of the Microbiome Impacts Health And Diseasementioning

confidence: 99%

Host genetic control of gut microbiome composition

2021

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The gut microbiome plays a significant role in health and disease, and there is mounting evidence indicating that the microbial composition is regulated in part by host genetics. Heritability estimates for microbial abundance in mice and humans range from (0.05–0.45), indicating that 5–45% of inter-individual variation can be explained by genetics. Through twin studies, genetic association studies, systems genetics, and genome-wide association studies (GWAS), hundreds of specific host genetic loci have been shown to associate with the abundance of discrete gut microbes. Using genetically engineered knock-out mice, at least 30 specific genes have now been validated as having specific effects on the microbiome. The relationships among of host genetics, microbiome composition, and abundance, and disease is now beginning to be unraveled through experiments designed to test causality. The genetic control of disease and its relationship to the microbiome can manifest in multiple ways. First, a genetic variant may directly cause the disease phenotype, resulting in an altered microbiome as a consequence of the disease phenotype. Second, a genetic variant may alter gene expression in the host, which in turn alters the microbiome, producing the disease phenotype. Finally, the genetic variant may alter the microbiome directly, which can result in the disease phenotype. In order to understand the processes that underlie the onset and progression of certain diseases, future research must take into account the relationship among host genetics, microbiome, and disease phenotype, and the resources needed to study these relationships.

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“…Guardia-Escote et al 101 also showed that the composition of gut microbiota in early life can be modulated by the APOE genetic background. Environmental factors such as dietary habits, living conditions, and contamination of environmental matrices can also interact with genetic profiles to affect gut microbiota composition 93 , 102 .…”

Section: Genetic and Environmental Factors Affect Gut Microbiotamentioning

confidence: 99%

Genetic and environmental factors in Alzheimer’s and Parkinson’s diseases and promising therapeutic intervention via fecal microbiota transplantation

Wang

Feng

Zhang

et al. 2021

npj Parkinsons Dis.

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Neurodegenerative diseases are characterized by neuronal impairment and loss of function, and with the major shared histopathological hallmarks of misfolding and aggregation of specific proteins inside or outside cells. Some genetic and environmental factors contribute to the promotion of the development and progression of neurodegenerative diseases. Currently, there are no effective treatments for neurodegenerative diseases. It has been revealed that bidirectional communication exists between the brain and the gut. The gut microbiota is a changeable and experience-dependent ecosystem and can be modified by genetic and environmental factors. The gut microbiota provides potential therapeutic targets that can be regulated as new interventions for neurodegenerative diseases. In this review, we discuss genetic and environmental risk factors for neurodegenerative diseases, summarize the communication among the components of the microbiota-gut-brain axis, and discuss the treatment strategy of fecal microbiota transplantation (FMT). FMT is a promising treatment for neurodegenerative diseases, and restoration of the gut microbiota to a premorbid state is a novel goal for prevention and treatment strategies.

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Gut Microbiota between Environment and Genetic Background in Familial Mediterranean Fever (FMF)

Cited by 18 publications

References 188 publications

Gut Microbiota Dysbiosis Correlates with Abnormal Immune Response in Moderate COVID-19 Patients with Fever

Gut Microbiota Dysbiosis Correlates with Abnormal Immune Response in Moderate COVID-19 Patients with Fever

Host genetic control of gut microbiome composition

Genetic and environmental factors in Alzheimer’s and Parkinson’s diseases and promising therapeutic intervention via fecal microbiota transplantation

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