scholarly journals Phages in the Gut Ecosystem

Author(s):  
Michele Zuppi ◽  
Heather L. Hendrickson ◽  
Justin M. O’Sullivan ◽  
Tommi Vatanen

Phages, short for bacteriophages, are viruses that specifically infect bacteria and are the most abundant biological entities on earth found in every explored environment, from the deep sea to the Sahara Desert. Phages are abundant within the human biome and are gaining increasing recognition as potential modulators of the gut ecosystem. For example, they have been connected to gastrointestinal diseases and the treatment efficacy of Fecal Microbiota Transplant. The ability of phages to modulate the human gut microbiome has been attributed to the predation of bacteria or the promotion of bacterial survival by the transfer of genes that enhance bacterial fitness upon infection. In addition, phages have been shown to interact with the human immune system with variable outcomes. Despite the increasing evidence supporting the importance of phages in the gut ecosystem, the extent of their influence on the shape of the gut ecosystem is yet to be fully understood. Here, we discuss evidence for phage modulation of the gut microbiome, postulating that phages are pivotal contributors to the gut ecosystem dynamics. We therefore propose novel research questions to further elucidate the role(s) that they have within the human ecosystem and its impact on our health and well-being.

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1015-1015
Author(s):  
Julie Jeon ◽  
Xi Fang ◽  
Jeferson Lourenco ◽  
Srujana Rayalam ◽  
Michael Rothrock ◽  
...  

Abstract Objectives Microbial programming in early life is associated with gut health and overall well-being in adulthood. The establishment of the nascent gut microbiome is substantially influenced by both maternal nutrition and the native maternal microbiome. Pig is recognized as a valuable model in gastrointestinal track research due to its remarkable similarity to humans in gastrointestinal anatomy, physiology, biochemistry, immunology, and pathology. This study examined the characteristics of the gut microflora in the sow-piglet dyad. Methods Fecal samples were collected from sows (n = 6) and piglets (n = 24) at weaning. Bacterial DNA was isolated from the feces and the V3-V4 region of 16 s rRNA gene was amplified and sequenced using the Illumina Miseq platform and analyzed by QIIME pipeline. Results Sows had a twice higher abundance of Firmicutes than piglets (84.28% vs 40.19%, P < 0.0001), although Firmicutes was the most abundant phyla in both sows and piglets. Instead, piglets had higher abundances of Bacteroidetes (36.41% vs 9.61%, P < 0.0001) and Proteobacteria (11.31% vs 0.87%, P = 0.005) than sows. Early colonization of Proteobacteria has been suggested to be important for development of neonatal immunity. Firmicutes to Bacteroidetes ratio was higher in sows than in piglets (16.32 vs 1.36, P < 0.0001), which is consistent with previous reports in humans. The five most abundant families in sows were Clostridiaceae (30.43%), Turicibacteraceae (17.13%), Ruminococcaceae (11.29%), Lactobacillaceae (8.27%), and Lachnospiraceae (4.99%), while those in piglets were Bacteroidaceae (23.96%), Lachnospiraceae (9.13%), Clostridiaceae (7.52%), Ruminococcaceae (6.80%), and Enterobacteriaceae (6.63%). Observed OTUs in sows were higher (P = 0.02) than those in piglets, suggesting that piglets at early stage of life have lower fecal α-diversity. Moreover, β-diversity was very different between sows and piglets (P = 0.01). Conclusions Sows and piglets showed distinctive pattern of fecal microflora, and piglets had fewer species numbers at weaning compared to that of sows. This finding will provide a valuable information for future transgenerational studies on the gut microbiome and its consequences for health using a sow-piglet dyad. Funding Sources Georgia Experimental Agricultural Station, UGA Faculty research grant, and Center for Chronic Disorders of Aging at the PCOM.


2016 ◽  
Vol 30 (1) ◽  
pp. 191-231 ◽  
Author(s):  
Lauren E. Hudson ◽  
Sarah E. Anderson ◽  
Anita H. Corbett ◽  
Tracey J. Lamb

SUMMARY Beneficial microorganisms hold promise for the treatment of numerous gastrointestinal diseases. The transfer of whole microbiota via fecal transplantation has already been shown to ameliorate the severity of diseases such as Clostridium difficile infection, inflammatory bowel disease, and others. However, the exact mechanisms of fecal microbiota transplant efficacy and the particular strains conferring this benefit are still unclear. Rationally designed combinations of microbial preparations may enable more efficient and effective treatment approaches tailored to particular diseases. Here we use an infectious disease, C. difficile infection, and an inflammatory disorder, the inflammatory bowel disease ulcerative colitis, as examples to facilitate the discussion of how microbial therapy might be rationally designed for specific gastrointestinal diseases. Fecal microbiota transplantation has already shown some efficacy in the treatment of both these disorders; detailed comparisons of studies evaluating commensal and probiotic organisms in the context of these disparate gastrointestinal diseases may shed light on potential protective mechanisms and elucidate how future microbial therapies can be tailored to particular diseases.


Science ◽  
2021 ◽  
Vol 371 (6529) ◽  
pp. 595-602 ◽  
Author(s):  
Diwakar Davar ◽  
Amiran K. Dzutsev ◽  
John A. McCulloch ◽  
Richard R. Rodrigues ◽  
Joe-Marc Chauvin ◽  
...  

Anti–programmed cell death protein 1 (PD-1) therapy provides long-term clinical benefits to patients with advanced melanoma. The composition of the gut microbiota correlates with anti–PD-1 efficacy in preclinical models and cancer patients. To investigate whether resistance to anti–PD-1 can be overcome by changing the gut microbiota, this clinical trial evaluated the safety and efficacy of responder-derived fecal microbiota transplantation (FMT) together with anti–PD-1 in patients with PD-1–refractory melanoma. This combination was well tolerated, provided clinical benefit in 6 of 15 patients, and induced rapid and durable microbiota perturbation. Responders exhibited increased abundance of taxa that were previously shown to be associated with response to anti–PD-1, increased CD8+ T cell activation, and decreased frequency of interleukin-8–expressing myeloid cells. Responders had distinct proteomic and metabolomic signatures, and transkingdom network analyses confirmed that the gut microbiome regulated these changes. Collectively, our findings show that FMT and anti–PD-1 changed the gut microbiome and reprogrammed the tumor microenvironment to overcome resistance to anti–PD-1 in a subset of PD-1 advanced melanoma.


2018 ◽  
Author(s):  
Cristina M. Herren ◽  
Michael Baym

AbstractBacterial infection in the gut is often due to successful invasion of the host microbiome by an introduced pathogen. Ecological theory indicates that resident community members and their interactions should be strong determinants of whether an invading taxon can persist in a community. In the context of the gut microbiome, this suggests colonization resistance against newly introduced bacteria should depend on the instantaneous bacterial community composition within the gut and interactions between these constituent members. Here we develop a mathematical model of how metabolite-dependent biotic interactions between resident bacteria mediate invasion, and find that stronger biotic connectivity from metabolite cross-feeding and competition increases colonization resistance. We then introduce a statistical method for identifying invasive taxa in the human gut, and show empirically that greater connectivity of the resident gut microbiome is related to increased resistance to invading bacteria. Finally, we examined patient outcomes after fecal microbiota transplant (FMT) for recurring Clostridium difficile infection. Patients with lower connectivity of the gut microbiome after treatment were more likely to relapse, experiencing a later infection. Thus, simulation models and data from human subjects support the hypothesis that stronger interactions between bacteria in the gut repel invaders. These results demonstrate how ecological invasion theory can be applied to the gut microbiome, which might inform targeted microbiome manipulations and interventions. More broadly, this study provides evidence that low connectivity in gut microbial communities is a hallmark of community instability and susceptibility to invasion.


2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Wei-jie Lv ◽  
Xiao-ling Wu ◽  
Wen-qian Chen ◽  
Yue-fei Li ◽  
Gui-feng Zhang ◽  
...  

Generally, depression is the result of complex gene-environment interactions. Recent studies have showed that the gut microbiota can affect brain function through the microbiota-gut-brain axis. However, the underlying mechanism of the microbiota and potential influence of depression remain elusive. We aimed to determine how gut microbiome contributes to the process of depression and further influences the host. Chronic unpredictable mild stress (CUMS) is used to establish a depression model. Fecal microbiota transplant (FMT) is applied to illustrate that depression can be transmitted via microbiota, and metabolism of liver analysis is applied to demonstrate further influence to the liver. We also analyzed the astrocyte activation in the brain by immunofluorescence (IF). Here, we show that the structure of the gut microbiome changes markedly after rats undergo CUMS. Notably, we found that the ratio of Lactobacillus to Clostridium can be a vital index for the development of depression. Depression-like behavior can be duplicated through FMT. Moreover, increased zonulin and fatty acid binding protein-2 indicates that gut barrier integrity is broken after FMT. Subsequently, metabolomics shows that liver metabolic disorder occurs and leads to liver coagulative necrosis. In addition, increased inflammatory cytokine expression and higher astrocyte activation indicate an inflammatory process in the brain. These findings suggest that dysbiosis gut microbiome contributes to development of depression and further causes liver metabolic disorders in a way that may be relevant to the Lactobacillus to Clostridium ratio.


2019 ◽  
Vol 30 (8) ◽  
pp. 795-805 ◽  
Author(s):  
Andrew Octavian Sasmita

Abstract The gut microbiome was extensively researched for its biological variety and its potential role in propagating diseases outside of the gastrointestinal (GI) tract. Recently, a lot of effort was focused on comprehending the gut-brain axis and the bizarre communication between the GI system and the nervous system. Ample amount of studies being carried out also revealed the involvement of the gut microbiome in enhancing the degree of many neurological disorders, including neurodegenerative diseases. It was widely observed that there were distinct microbiome profiles and dysbiosis within patients suffering from Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis. Various approaches to re-establish the balance of the gut microbiome, from antibiotic therapy, fecal microbiota transplant, or ingestion of psychobiotics, are discussed within this review within the specific context of combating neurodegenerative diseases. Present studies and clinical trials indicate that although there is an immense potential of gut microbiome modification to be preventive or therapeutic, there are still many intercalated components of the gut-brain axis at play and thus, more research needs to be carried out to delineate microbiome factors that may potentially alleviate symptoms of neurodegeneration.


2021 ◽  
Vol 22 (22) ◽  
pp. 12506
Author(s):  
Adi Eindor-Abarbanel ◽  
Genelle R. Healey ◽  
Kevan Jacobson

There is mounting evidence that the gut microbiota plays an important role in the pathogenesis of inflammatory bowel disease (IBD). For the past decade, high throughput sequencing-based gut microbiome research has identified characteristic shifts in the composition of the intestinal microbiota in patients with IBD, suggesting that IBD results from alterations in the interactions between intestinal microbes and the host’s mucosal immune system. These studies have been the impetus for the development of new therapeutic approaches targeting the gut microbiome, such as nutritional therapies, probiotics, fecal microbiota transplant and beneficial metabolic derivatives. Innovative technologies can further our understanding of the role the microbiome plays as well as help to evaluate how the different approaches in microbiome modulation impact clinical responses in adult and pediatric patients. In this review, we highlight important microbiome studies in patients with IBD and their response to different microbiome modulation therapies, and describe the differences in therapeutic response between pediatric and adult patient cohorts.


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