Individuals at risk for rheumatoid arthritis harbor differential intestinal bacteriophage communities with distinct metabolic potential

Mangalea, Mihnea R.; Páez-Espino, David; Kieft, Kristopher; Chatterjee, Anushila; Chriswell, Meagan E.; Seifert, Jennifer; Feser, Marie L.; Demoruelle, M. Kristen; Sakatos, Alexandra; Anantharaman, Karthik; Deane, Kevin D.; Kuhn, Kristine A.; Holers, V. Michael; Duerkop, Breck A.

doi:10.1016/j.chom.2021.03.020

Cited by 59 publications

(48 citation statements)

References 104 publications

(115 reference statements)

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“…The standard DESeq2 workflow was performed, using "poscounts" for estimation of size factors. In each comparison, scaffolds with adjusted p-values < 0.001 and with log 2 fold changes greater or less than 1 were considered differentially abundant 85 . Bray-Curtis dissimilarity and Jaccard distances for diversity analyses were performed on matrices normalized by total coverage using Vegan v2.5-7.…”

Section: Bioinformatic Analysis Of Vlp Sequence Datamentioning

confidence: 99%

“…Dots shown in the volcano plots represent the differentially abundant scaffolds found during the VLP gavage period. Scaffolds with adjusted p-values < 0.001 and with log2fold changes greater or less than 1 were considered differentially abundant using a two-tailed wald test85 . Data shown are from the first of two independent trials represented in Fig.1B(trial #1).…”

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confidence: 99%

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Transplantation of bacteriophages from ulcerative colitis patients shifts the gut bacteriome and exacerbates severity of DSS-colitis

Sinha

Mirzaei

et al. 2021

Preprint

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Inflammatory bowel diseases (IBDs) including Crohn's disease (CD) and ulcerative colitis (UC) are characterized by chronic and debilitating gut inflammation. Altered bacterial communities of the intestine are strongly associated with IBD initiation and progression. The gut virome, which is primarily composed of bacterial viruses (bacteriophages, phages) is thought to be an important factor regulating and shaping microbial communities in the gut. While alterations in the gut virome have been observed in IBD patients, the contribution of these viruses to alterations in the bacterial community and heightened inflammatory responses associated with IBD patients remains largely unknown. Here, we performed in vivo microbial cross-infection experiments to follow the effects of fecal virus-like particles (VLPs) isolated from UC patients and healthy controls on bacterial diversity and severity of experimental colitis in human microbiota-associated (HMA) mice. Shotgun metagenomics confirmed that several phages were transferred to HMA mice, resulting in treatment-specific alterations in the gut virome. VLPs from healthy and UC patients also shifted gut bacterial diversity of these mice, an effect that was amplified during experimental colitis. VLPs isolated from UC patients specifically altered the relative abundance of several bacterial taxa previously implicated in IBD progression. Additionally, UC VLP administration heightened colitis severity in HMA mice, as indicated by shortened colon length and increased pro-inflammatory cytokine production. Importantly, this effect was dependent on intact VLPs. Our findings build on recent literature indicating that phages are dynamic regulators of bacterial communities in the gut and implicate the intestinal virome in modulating intestinal inflammation and disease.

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Section: Bioinformatic Analysis Of Vlp Sequence Datamentioning

confidence: 99%

mentioning

confidence: 99%

Transplantation of bacteriophages from ulcerative colitis patients shifts the gut bacteriome and exacerbates severity of DSS-colitis

Sinha

Mirzaei

et al. 2021

Preprint

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“…The role of phages in the mammalian gut is an emergent area of research relevant to diseases including inflammatory bowel disease ( 2 ), rheumatoid arthritis ( 3 ), colorectal cancer ( 4 ), and Clostridioides difficile infections (CDI) ( 5 ). A key consideration is whether alterations in the phage community contribute to or result from disease.…”

Section: Bacteriophages—bacterial Grazing or Devouringmentioning

confidence: 99%

Towards the Characterization and Engineering of Bacteriophages in the Gut Microbiome

Hsu

2021

mSystems

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“…Though the virome consists of both bacteriophages (phages), as well as eukaryotic viruses, we will refer to phages only when talking about the virome here. Shifts in the phage composition of the gut have been associated with an increasing number of diseases such as Crohn's disease and Ulcerative Colitis [17] as well as other conditions such as arthritis [18]. These phages are thought to be virulent, but previous work has suggested that the gut virome contains a significant proportion of temperate phages as well [19,20].…”

Section: Introductionmentioning

confidence: 99%

Prophages in the infant gut are largely induced, and may be functionally relevant to their hosts

Redgwell

Thorsen

Petit

et al. 2021

Preprint

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Background: Bacteriophages are the most abundant biological entity on the planet, and are key components of any ecosystem they are present in. The gut virome is increasingly being implicated in disease states although these studies largely focus on lytic phages in adults. Here we identify prophages from a large infant cohort and investigate their potential functions. Results: We identified 10645 vOTUs from 662 metagenomes. No core virome was found: the most prevalent vOTU was identified in 70% of the samples. The most abundant and prevalent group of phages are a novel group closely related to Bacteroides phage Hanky p00. Functional annotation of this group revealed the presence of genes in the dDTP-L-rhamnose pathway, possibly involved in the production of capsular polysaccharides. We also found an abundance of diversity generating retroelements in the phages. Additionally, paired virome data allowed us to show that the majority of prophages are induced in at least one sample and that this is not affected by the use of antibiotics in the 4 weeks prior to sampling. Conclusions: Prophages in the infant gut are largely unique to the individual and not shared. Most of them appear to be induced and so may be key drivers in shaping the bacterial microbiome. The most abundant group of phages are novel, and possess elements that may allow them to maintain differentially susceptible subpopulations of their host bacterium; whilst also containing diversity generating retroelements that could expand their host range. Prophages are important components of the infant gut that may have far reaching influences on the composition and function of the microbiome.

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Individuals at risk for rheumatoid arthritis harbor differential intestinal bacteriophage communities with distinct metabolic potential

Cited by 59 publications

References 104 publications

Transplantation of bacteriophages from ulcerative colitis patients shifts the gut bacteriome and exacerbates severity of DSS-colitis

Transplantation of bacteriophages from ulcerative colitis patients shifts the gut bacteriome and exacerbates severity of DSS-colitis

Towards the Characterization and Engineering of Bacteriophages in the Gut Microbiome

Prophages in the infant gut are largely induced, and may be functionally relevant to their hosts

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