Fecal Viral Community Responses to High-Fat Diet in Mice.

Alterations in diet can have significant impact on the host, with high-fat diet (HFD) leading to obesity, diabetes, and inflammation of the gut. Although membership and abundances in gut bacterial communities are strongly influenced by diet, substantially less is known about how viral communities respond to dietary changes. Examining fecal contents of mice as the mice were transitioned from normal chow to HFD, we found significant changes in the relative abundances and the diversity in the gut of bacteria and their viruses. Alpha diversity of the bacterial community was significantly diminished in response to the diet change but did not change significantly in the viral community. However, the diet shift significantly impacted the beta diversity in both the bacterial and viral communities. There was a significant shift away from the relatively abundant Siphoviridae accompanied by increases in bacteriophages from the Microviridae family. The proportion of identified bacteriophage structural genes significantly decreased after the transition to HFD, with a conserved loss of integrase genes in all four experimental groups. In total, this study provides evidence for substantial changes in the intestinal virome disproportionate to bacterial changes, and with alterations in putative viral lifestyles related to chromosomal integration as a result of shift to HFD.IMPORTANCE Prior studies have shown that high-fat diet (HFD) can have profound effects on the gastrointestinal (GI) tract microbiome and also demonstrate that bacteria in the GI tract can affect metabolism and lean/obese phenotypes. We investigated whether the composition of viral communities that also inhabit the GI tract are affected by shifts from normal to HFD. We found significant and reproducible shifts in the content of GI tract viromes after the transition to HFD. The differences observed in virome community membership and their associated gene content suggest that these altered viral communities are populated by viruses that are more virulent toward their host bacteria. Because HFD also are associated with significant shifts in GI tract bacterial communities, we believe that the shifts in the viral community may serve to drive the changes that occur in associated bacterial communities

A eudicot MIXTA family ancestor likely functioned in both conical cells and trichomes

The MIXTA family of MYB transcription factors modulate the development of diverse epidermal features in land plants. This study investigates the evolutionary history and function of the MIXTA gene family in the early-diverging eudicot model lineage Thalictrum (Ranunculaceae), with R2R3 SBG9-A MYB transcription factors representative of the pre-core eudicot duplication and thus hereby referred to as “paleoMIXTA” (PMX). Cloning and phylogenetic analysis of Thalictrum paleoMIXTA (ThPMX) orthologs across 23 species reveal a genus-wide duplication coincident with a whole-genome duplication. Expression analysis by qPCR confirmed that the highest expression is found in carpels, while newly revealing high expression in leaves and nuanced differences between paralogs in representative polyploid species. The single-copy ortholog from the diploid species T. thalictroides (TthPMX, previously TtMYBML2), which has petaloid sepals with conical–papillate cells and trichomes on leaves, was functionally characterized by virus-induced gene silencing (VIGS), and its role in leaves was also assessed from heterologous overexpression in tobacco. Another ortholog from a species with conical–papillate cells on stamen filaments, TclPMX, was also targeted for silencing. Overexpression assays in tobacco provide further evidence that the paleoMIXTA lineage has the potential for leaf trichome function in a core eudicot. Transcriptome analysis by RNA-Seq on leaves of VIGS-treated plants suggests that TthPMX modulates leaf trichome development and morphogenesis through microtubule-associated mechanisms and that this may be a conserved pathway for eudicots. These experiments provide evidence for a combined role for paleoMIXTA orthologs in (leaf) trichomes and (floral) conical–papillate cells that, together with data from other systems, makes the functional reconstruction of a eudicot ancestor most likely as also having a combined function

Intergenerational transfer of antibiotic-perturbed microbiota enhances colitis in susceptible mice

Antibiotic exposure in children has been associated with the risk of Inflammatory Bowel Disease (IBD). Since antibiotic use in children or in their pregnant mother can affect how the intestinal microbiome develops, we asked whether the transfer of an antibiotic-perturbed microbiota from mothers to their children could affect their risk of developing IBD. Here we demonstrate that germ-free adult pregnant mice inoculated with a gut microbial community shaped by antibiotic exposure transmitted their perturbed microbiota to their offspring with high fidelity. Without any direct or continued exposure to antibiotics, this dysbiotic microbiota in the offspring remained distinct from controls for at least 21 weeks. By using both IL-10-deficient and wild type mothers, we showed that both inoculum and genotype shape the microbiota populations in the offspring. Since IL10−/− mice are genetically susceptible to colitis, we could assess the risk due to maternal transmission of an antibiotic-perturbed microbiota. We found that the IL10−/− offspring that had received the perturbed gut microbiota developed markedly increased colitis. Taken together, our findings indicate that antibiotic exposure shaping the maternal gut microbiota has effects that extend to their offspring with both ecological and long-term disease consequences

Antibiotic use and the risk of rheumatoid arthritis: a population-based case-control study

Background: Antibiotic-induced disturbances of the human microbiota have been implicated in the development of chronic autoimmune conditions. This study aimed to assess whether antibiotic use is associated with the onset of rheumatoid arthritis (RA). Methods: A nested case-control study was conducted utilising data from the primary care Clinical Practice Research Datalink (CPRD). Patients with an incident diagnosis of RA were identified (1995–2017). Each case was matched on age, gender, and general practice to ≥ 5 controls without RA. Conditional logistic regression was used to examine previous antibiotic prescriptions and RA onset after controlling for confounding factors. Results: We identified 22,677 cases of RA, matched to 90,013 controls, with a median follow-up of 10 years before RA diagnosis. The odds of developing RA were 60% higher in those exposed to antibiotics than in those not exposed (OR 1.60; 95% CI 1.51–1.68). A dose- or frequency-dependent association was observed between the number of previous antibiotic prescriptions and RA. All classes of antibiotics were associated with higher odds of RA, with bactericidal antibiotics carrying higher risk than bacteriostatic (45% vs. 31%). Those with antibiotic-treated upper respiratory tract (URT) infections were more likely to be RA cases. However, this was not observed for URT infections not treated with antibiotics. Antifungal (OR = 1.27; 95% CI 1.20–1.35) and antiviral (OR = 1.19; 95% CI 1.14–1.24) prescriptions were also associated with increased odds of RA. Conclusion: Antibiotic prescriptions are associated with a higher risk of RA. This may be due to microbiota disturbances or underlying infections driving risk. Further research is needed to explore these mechanisms

Impact of antibiotics on long-term physiology through microbiota changes.

<p>The gut microbiota has been shown to influence the development of the host’s immune system in addition to being implicated in adipose, muscle, and bone tissue growth. New evidence indicating the gut microbiota may impact stem-like cell populations suggests a new way in which the gut microbiota may be regulating tissue development. Antibiotics alter the gut microbiota, which may change the course of these developmental pathways, leading to variations in long-term physiology.</p

Fecal Viral Community Responses to High-Fat Diet in Mice.

Alterations in diet can have significant impact on the host, with high-fat diet (HFD) leading to obesity, diabetes, and inflammation of the gut. Although membership and abundances in gut bacterial communities are strongly influenced by diet, substantially less is known about how viral communities respond to dietary changes. Examining fecal contents of mice as the mice were transitioned from normal chow to HFD, we found significant changes in the relative abundances and the diversity in the gut of bacteria and their viruses. Alpha diversity of the bacterial community was significantly diminished in response to the diet change but did not change significantly in the viral community. However, the diet shift significantly impacted the beta diversity in both the bacterial and viral communities. There was a significant shift away from the relatively abundant Siphoviridae accompanied by increases in bacteriophages from the Microviridae family. The proportion of identified bacteriophage structural genes significantly decreased after the transition to HFD, with a conserved loss of integrase genes in all four experimental groups. In total, this study provides evidence for substantial changes in the intestinal virome disproportionate to bacterial changes, and with alterations in putative viral lifestyles related to chromosomal integration as a result of shift to HFD.IMPORTANCE Prior studies have shown that high-fat diet (HFD) can have profound effects on the gastrointestinal (GI) tract microbiome and also demonstrate that bacteria in the GI tract can affect metabolism and lean/obese phenotypes. We investigated whether the composition of viral communities that also inhabit the GI tract are affected by shifts from normal to HFD. We found significant and reproducible shifts in the content of GI tract viromes after the transition to HFD. The differences observed in virome community membership and their associated gene content suggest that these altered viral communities are populated by viruses that are more virulent toward their host bacteria. Because HFD also are associated with significant shifts in GI tract bacterial communities, we believe that the shifts in the viral community may serve to drive the changes that occur in associated bacterial communities