Microbiota, Disease, and Back to Health: A Metastable Journey

Blumberg, Richard S.; Powrie, Fiona

doi:10.1126/scitranslmed.3004184

Cited by 258 publications

(219 citation statements)

References 98 publications

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“…1 Although the host provides the microbiota with the ecological niche and nutrients required of its survival, the indigenous microbiota, in turn, provides the host with full maturation of the innate and adaptive arms of the immune system, modulation of the nervous system function, nutrient absorption and fat distribution, contribution to digestion (eg, the ability of microbes to break down host nondigestible polysaccharides), the generation of short-chain fatty acids (SCFAs), metabolism of xenobiotics (which aids in protection from environmental toxins), and regulation of the gut motility. 2,[22][23][24][25] Colonization resistance is another protective function that the microbes provide to their host. This protective function results from a combination of various functions of commensals, which include their metabolic competition with the pathogen for the available nutrient resources.…”

Section: The Host-microbiota Dialoguementioning

confidence: 99%

Gut Microbiota: The Conductor in the Orchestra of Immune–Neuroendocrine Communication

Aidy

Dinan

Cryan

2015

Clinical Therapeutics

175

100

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Section: The Host-microbiota Dialoguementioning

confidence: 99%

Gut Microbiota: The Conductor in the Orchestra of Immune–Neuroendocrine Communication

Aidy

Dinan

Cryan

2015

Clinical Therapeutics

175

100

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“…The above studies suggest that gut dysbiosis and the related increased permeability of the gut could serve as environmental factors for the development of obesity before the development of diabetes. While data from mice are convincing, the functional links between human gut microbiota and disease are less well-understood because of various confounding factors, including age, sex, diet, genetics, and race (14,15).…”

mentioning

confidence: 99%

Gut Dysbiosis and Detection of “Live Gut Bacteria” in Blood of Japanese Patients With Type 2 Diabetes

et al. 2014

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OBJECTIVEMounting evidence indicates that the gut microbiota are an important modifier of obesity and diabetes. However, so far there is no information on gut microbiota and "live gut bacteria" in the systemic circulation of Japanese patients with type 2 diabetes. RESEARCH DESIGN AND METHODSUsing a sensitive reverse transcription-quantitative PCR (RT-qPCR) method, we determined the composition of fecal gut microbiota in 50 Japanese patients with type 2 diabetes and 50 control subjects, and its association with various clinical parameters, including inflammatory markers. We also analyzed the presence of gut bacteria in blood samples. RESULTSThe counts of the Clostridium coccoides group, Atopobium cluster, and Prevotella (obligate anaerobes) were significantly lower (P < 0.05), while the counts of total Lactobacillus (facultative anaerobes) were significantly higher (P < 0.05) in fecal samples of diabetic patients than in those of control subjects. Especially, the counts of Lactobacillus reuteri and Lactobacillus plantarum subgroups were significantly higher (P < 0.05). Gut bacteria were detected in blood at a significantly higher rate in diabetic patients than in control subjects (28% vs. 4%, P < 0.01), and most of these bacteria were Gram-positive.

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“…28 In this work, motivated by the burgeoning interest in the impact of the gut microbiome on human health and disease, [40][41][42][43] we extracted a large spacer catalog from metagenomic sequences of gut-residing bacteria. 44 Using these spacers as "baits" to identify contigs derived from phage DNA, we detected almost 1,000 gut-associated phage genomes, many of which appeared in multiple individuals and also across gut samples taken from Americans and Japanese.…”

Section: Holding a Grudgementioning

confidence: 99%

Holding a grudge

2013

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T he CRISPR (clustered regularlyinterspaced short palindromic repeats)/Cas (CRISPR-associated) system of bacteria and archaea constitutes a mechanism of acquired adaptive immunity against phages, which is based on genome-encoded markers of previously infecting phage sequences ("spacers"). As a repository of phage sequences, these spacers make the system particularly suitable for elucidating phage-bacteria interactions in metagenomic studies. Recent metagenomic analyses of CRISPRs associated with the human microbiome intriguingly revealed conserved "memory spacers" shared by bacteria in multiple unrelated, geographically separated individuals. Here, we discuss possible avenues for explaining this phenomenon by integrating insights from CRISPR biology and phage-bacteria ecology, with a special focus on the human gut. We further explore the growing body of evidence for the role of CRISPR/Cas in regulating the interplay between bacteria and lysogenic phages, which may be intimately related to the presence of memory spacers and sheds new light on the multifaceted biological and ecological modes of action of CRISPR/Cas. IntroductionBacteriophages are known to play a crucial role in shaping the structure, diversity and evolution of microbial communities in various ecological niches. [1][2][3][4] The CRISPR (clustered regularly interspaced short palindromic repeats)/Cas Holding a grudgePersisting anti-phage CRISPR immunity in multiple human gut microbiomes (CRISPR-associated) system of bacteria and archaea constitutes a mechanism of acquired adaptive immunity against phages, which is based on genomeencoded markers of past infections. 5 The unique biology of this system has opened a window into the multifaceted interactions that take place in natural environments between microbial populations and their associated phages. At the same time, observation of these interactions raises intriguing questions about the underlying mechanistic activity of CRISPR/Cas. Here, we explore this reciprocity with a focus on the microbial community resident in the human gut.CRISPR loci are composed of a succession of short repeat sequences separated by unique "spacer" sequences, usually sized 24-50 bp. While the mechanism of action of the CRISPR/Cas system is not yet fully characterized and some specifics vary by subtype, it generally entails three processes: incorporation of fragments of phage or plasmid genomes as novel spacers in bacterial CRISPR arrays; transcription and processing of the array into small RNAs (crRNAs) and formation of a crRNA/Cas protein complex that recognizes foreign nucleic acids through sequence complementarity and interferes with phage replication. [6][7][8][9][10][11] Elucidation of the function of the CRISPR/Cas system has led to theoretical and experimental efforts at exploring the ecological impacts of CRISPR-mediated immunity, as well as the conditions under which its emergence would be favored. [12][13][14] However, this system provided an ©2012 Landes Bioscience. Do not distribute.

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Microbiota, Disease, and Back to Health: A Metastable Journey

Cited by 258 publications

References 98 publications

Gut Microbiota: The Conductor in the Orchestra of Immune–Neuroendocrine Communication

Gut Microbiota: The Conductor in the Orchestra of Immune–Neuroendocrine Communication

Gut Dysbiosis and Detection of “Live Gut Bacteria” in Blood of Japanese Patients With Type 2 Diabetes

Holding a grudge

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