A Gut Microbial Peptide and Molecular Mimicry in the Pathogenesis of Type 1 Diabetes

Girdhar, Khyati; Huang, Qian; Chow, I-Ting; Brady, Claudia; Raisingani, Amol; Autissier, Patrick; Atkinson, Mark A.; Kwok, William W.; Kahn, C. Ronald; Altındiş, Emrah

doi:10.1101/2020.10.22.350801

Cited by 3 publications

(5 citation statements)

References 112 publications

(150 reference statements)

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“…Table 2 summarizes the results of searching for molecular mimicry in the analyzed genomes to identify the presence of insulin B chain insB:9–23 peptide mimics (SHLVEALYLVCGERG) [ 48 ], and the two microbial altered peptide ligands (MVWGPDPLYV and RQFGPDWIVA) from the natural preproinsulin (ALWGPDPAAA) [ 50 ]. A variant of the insB:9–23 peptide (HL L EALY MTY GE) was identified only in the genome of B. uniformis PtF Sb3P5.…”

Section: Resultsmentioning

confidence: 99%

“…Interestingly, Falony et al [ 62 ] found an increase in Parabacteroides in individuals with low microbiome diversity that exhibited a preference for white, low fiber bread, and predominance of recent amoxicillin treatment. The recent reported molecular mimics of the human insulin B:9–23 peptide in P. distasonis 33B (from the human gut microbiome) [ 48 ] is an important warning for hidden autoimmune triggers. The genome of P. distasonis PtFD14MH1 did not show the presence of any variant of insB:9–23, however a variant of the Human Natural preproinsulin AWL, that is very similar to a previously described variant in C. asparagiforme, was identified [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

“…The genome of P. distasonis PtFD14MH1 did not show the presence of any variant of insB:9–23, however a variant of the Human Natural preproinsulin AWL, that is very similar to a previously described variant in C. asparagiforme, was identified [ 49 ]. The role of P. distasonis in host health is still controversial, namely while Huang et al [ 48 ] reported the stimulation by P. distasonis 33B of the human T cell clones specific to insB:9–23 and the colonization of the gut of female NOD mice with P. distasonis 33B stimulate T1D onset, Wang et al [ 63 ] reported that the treatment of obese mice with live P. distasonis resulted in an increase in the concentration of succinate in the jejunum, together with the activation of intestinal gluconeogenesis, diminishing food intake, and amelioration of glucose homeostasis. Other beneficial features of P. distasonis, is its ability to mitigate obesity-driven colorectal tumorigenesis and attenuate intestinal inflammation [ 64 , 65 ].…”

Section: Discussionmentioning

confidence: 99%

“…The identification of the potential pathogenicity to human host was conducted using the software PathogenFinder 1.1 [ 47 ]. The molecular mimicry identification was conducted using BLASTP (version 2.2.26) through SEED Viewer (version 2.0) by searching the presence of the insulin B chain insB:9–23 peptide mimics (SHLVEALYLVCGERG) described in P. distasonis 33B, which was found in the Human Gut Microbiome [ 48 ], and the two microbial altered peptides ligands (MVWGPDPLYV and RQFGPDWIVA) of the natural preproinsulin (ALWGPDPAAA) reported in Bacteroides fragilis / thetaiotaomicron and Clostridium asparagiforme , respectively [ 49 ].…”

Section: Methodsmentioning

confidence: 99%

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Insights from Bacteroides Species in Children with Type 1 Diabetes

Matos

Calha

et al. 2021

Microorganisms

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In our previous study the enrichment of the intestinal proteome of type 1 diabetes (T1D) children with Bacteroides proteins was observed, which led us to our current study that aimed to isolate and characterize Bacteroides species from fecal samples of T1D and control children. Repetitive sequence-based PCR (rep-PCR) was used for typing the isolated Bacteroides species. The antibiotic susceptibility and mucinolytic activity of the isolates was determined. The quantification of specific bacterial groups in the fecal samples was determined by qPCR. The ability to adhere and invade the human colonic cell line HT29-MTX-E12 of strains of P. dorei, B. uniformis and P. distasonis was determined and their whole genome sequencing was performed. The results showed similar numbers of Bacteroides species in T1D and control samples, but unique Bacteroides species and a higher recovery of P. distasonis from T1D samples was observed. Rep-PCR grouped the different Bacteroides species, but no discrimination by origin was achieved. T1D children showed a significant increase in Proteobacteria and a depletion in Lactobacillus sp. All tested P. dorei, B. uniformis and P. distasonis were able to adhere to HT29-MTX-E12 cells but significant differences (p < 0.05) in the ability to invade was observed. The highest ability to invade was exhibited by P. distasonis PtF D14MH1 and P. dorei PtFD16P1, while B. uniformis strains were unable to invade. The damage to tight junctions was also observed. The presence of Lactobacillus sp. inhibited the invasion ability of P. distasonis PtF D14MH1 but not P. dorei PtFD16P1. Sequences of agonist peptides of the human natural preproinsulin and the insulin B chain insB:9-23 peptide mimics were identified. The results reported in our study stresses the continued efforts required to clarify the link between T1D and gut microbiota.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Insights from Bacteroides Species in Children with Type 1 Diabetes

Matos

Calha

et al. 2021

Microorganisms

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“…Using a local BlastP library, we searched for the presence of peptide sequences with high sequence similarity to 62 human peptide hormones and regulatory proteins (88). We identified viral sequences that showed significant similarity with 16 different human peptide hormones, including insulin, insulin-like growth factors 1 and 2 (IGF-1 and IGF-2), tumor necrosis factor, endothelin-1 and -2, interleukin 6, and adiponectin (88,89). Until we discovered viral hormones, viral mimicry examples were limited to immunomodulatory proteins and growth factors (90)(91)(92)(93)(94)(95).…”

Section: A Novel Mechanism To Manipulate Host Metabolism: Discovery Of Viral Insulin and Insulin-like Growth Factor-like Peptidesmentioning

confidence: 99%

Viruses and Metabolism: The Effects of Viral Infections and Viral Insulins on Host Metabolism

et al. 2021

Self Cite

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Over the past decades, there have been tremendous efforts to understand the cross-talk between viruses and host metabolism. Several studies have elucidated the mechanisms through which viral infections manipulate metabolic pathways including glucose, fatty acid, protein, and nucleotide metabolism. These pathways are evolutionarily conserved across the tree of life and extremely important for the host's nutrient utilization and energy production. In this review, we focus on host glucose, glutamine, and fatty acid metabolism and highlight the pathways manipulated by the different classes of viruses to increase their replication. We also explore a new system of viral hormones in which viruses mimic host hormones to manipulate the host endocrine system. We discuss viral insulin/IGF-1-like peptides and their potential effects on host metabolism. Together, these pathogenesis mechanisms targeting cellular signaling pathways create a multidimensional network of interactions between host and viral proteins. Defining and better understanding these mechanisms will help us to develop new therapeutic tools to prevent and treat viral infections.

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Exploring the Triple Interaction between the Host Genome, the Epigenome, and the Gut Microbiome in Type 1 Diabetes

Elhag

Kumar

Khodor

2020

IJMS

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Type 1 diabetes (T1D) is an auto-immune disorder characterized by a complex interaction between the host immune system and various environmental factors in genetically susceptible individuals. Genome-wide association studies (GWAS) identified different T1D risk and protection alleles, however, little is known about the environmental factors that can be linked to these alleles. Recent evidence indicated that, among those environmental factors, dysbiosis (imbalance) in the gut microbiota may play a role in the pathogenesis of T1D, affecting the integrity of the gut and leading to systemic inflammation and auto-destruction of the pancreatic β cells. Several studies have identified changes in the gut microbiome composition in humans and animal models comparing T1D subjects with controls. Those changes were characterized by a higher abundance of Bacteroides and a lower abundance of the butyrate-producing bacteria such as Clostridium clusters IV and XIVa. The mechanisms by which the dysbiotic bacteria and/or their metabolites interact with the genome and/or the epigenome of the host leading to destructive autoimmunity is still not clear. As T1D is a multifactorial disease, understanding the interaction between different environmental factors such as the gut microbiome, the genetic and the epigenetic determinants that are linked with the early appearance of autoantibodies can expand our knowledge about the disease pathogenesis. This review aims to provide insights into the interaction between the gut microbiome, susceptibility genes, epigenetic factors, and the immune system in the pathogenesis of T1D.

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A Gut Microbial Peptide and Molecular Mimicry in the Pathogenesis of Type 1 Diabetes

Cited by 3 publications

References 112 publications

Insights from Bacteroides Species in Children with Type 1 Diabetes

Insights from Bacteroides Species in Children with Type 1 Diabetes

Viruses and Metabolism: The Effects of Viral Infections and Viral Insulins on Host Metabolism

Exploring the Triple Interaction between the Host Genome, the Epigenome, and the Gut Microbiome in Type 1 Diabetes

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