Rapid advances in DNA sequencing, metabolomics, proteomics and computational tools are dramatically increasing access to the microbiome and identification of its links with disease. In particular, time-series studies and multiple molecular perspectives are facilitating microbiome-wide association studies, which are analogous to genome-wide association studies. Early findings point to actionable outcomes of microbiome-wide association studies, although their clinical application has yet to be approved. An appreciation of the complexity of interactions among the microbiome and the host's diet, chemistry and health, as well as determining the frequency of observations that are needed to capture and integrate this dynamic interface, is paramount for developing precision diagnostics and therapies that are based on the microbiome.
At a glance
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This study linked the microbiota to IBD and also demonstrated that various forms of the condition have distinct signatures of microbiota.
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- Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res. 22, 292–298 (2012).
This study identified high levels of Fusobacterium nucleatum in tissue from human tumours; the bacterium was later confirmed to cause tumours in experiments in animals.
- Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. eLife 2, e01202 (2013).
This paper provided the first evidence to directly link the gut microbiota to rheumatoid arthritis in people.
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This study provided a mechanism to underpin the high variation between individuals in efficacy of the cardiac drug digoxin, which was suspected (but not yet proven) to be linked to its metabolism by Eggerthella lenta.
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This study of treatment-naive children who had been freshly diagnosed with Crohn's disease enabled the effects of treatment to be separated from those of the condition.
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This paper demonstrated how careful analysis of exact 16S rRNA sequences that avoids clustering into OTUs can reveal fine-grained information that can be useful for forensic matching.
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This study showed that the phenotype of a mouse model of autism spectrum disorder could be traced, in part, to a single molecule (4-ethylphenylsulfate) and a shift in the microbiota that can be partially restored using a probiotic.
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This paper compared two discordant studies of microbiomes in type 2 diabetes and showed that the alleged effect of diabetes could be attributed mostly to differences in use of metformin, which has an unexpectedly large effect on the microbiome, between the two populations.
- Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 341, 1241214 (2013).
This study demonstrated that phenotypes such as increased adiposity could be transferred from people to mice using personalized culture collections.
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- A systematic analysis of biosynthetic gene clusters in the human microbiome reveals a common family of antibiotics. Cell 158, 1402–1414 (2014).
This paper showed that the human microbiome harbours many biosynthetic gene clusters, including those required for the production of antibiotics.
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- Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nature Biotechnol. 31, 814–821 (2013). et al.
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- Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science 330, 831–835 (2010).
This paper demonstrated that the cancer therapeutic drug irinotecan causes severe diarrhoea because of its reactivation and metabolism by bacterial β-glucuronidases; inhibiting these enzymes with a drug that targets the bacteria, rather than the host, reduces toxicity.
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This study provided the first link between the toxicity of a drug (in this case, acetaminophen, a widely used analgesic) and microbial metabolism.
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- Ecological succession and viability of human-associated microbiota on restroom surfaces. Appl. Environ. Microbiol. 81, 765–773 (2015). et al.
- Growth dynamics of gut microbiota in health and disease inferred from single metagenomic samples. Science 349, 1101–1106 (2015). et al.
- Rapid draft sequencing and real-time nanopore sequencing in a hospital outbreak of Salmonella. Genome Biol. 16, 114 (2015). et al.
- Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. Nature Med. 22, 250–253 (2016). et al.
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- Network analysis suggests a potentially 'evil' alliance of opportunistic pathogens inhibited by a cooperative network in human milk bacterial communities. Sci. Rep. 5, 8275 (2015). et al.
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- EMPeror: a tool for visualizing high-throughput microbial community data. Gigascience 2, 16 (2013). , , &
- Dynamic changes in short- and long-term bacterial composition following fecal microbiota transplantation for recurrent Clostridium difficile infection. Microbiome 3, 10 (2015).
This paper introduced animation techniques that revealed the transformation of the whole microbiota during faecal microbiota transplantation for C. difficile infection.
- Succession of microbial consortia in the developing infant gut microbiome. Proc. Natl Acad. Sci. USA 108 (suppl. 1), 4578–4585 (2011). et al.
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- Temporal variability is a personalized feature of the human microbiome. Genome Biol. 15, 531 (2014). et al.
- Conditionally rare taxa disproportionately contribute to temporal changes in microbial diversity. mBio 5, e01371-14 (2014). et al.
- Temporal and spatial variation of the human microbiota during pregnancy. Proc. Natl Acad. Sci. USA 112, 11060–11065 (2015). et al.
- Host remodeling of the gut microbiome and metabolic changes during pregnancy. Cell 150, 470–480 (2012). et al.
- Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide. Eur. Heart J. 35, 904–910 (2014). et al.
- Personalized nutrition by prediction of glycemic responses. Cell 163, 1079–1094 (2015).
This study showed that individual glycaemic responses could be predicted using the microbiome; it also revealed that although population averages match conventional glycaemic-index values, the responses of individuals are highly idiosyncratic and dependent on the microbiome.
- Prediction of early childhood caries via spatial-temporal variations of oral microbiota. Cell Host Microbe 18, 296–306 (2015). et al.
- Predictive modeling of gingivitis severity and susceptibility via oral microbiota. ISME J. 8, 1768–1780 (2014). et al.
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- Vitamin B12 modulates the transcriptome of the skin microbiota in acne pathogenesis. Sci. Transl. Med. 7, 293ra103 (2015). , , , &
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- Fecal microbiota composition differs between children with β-cell autoimmunity and those without. Diabetes 62, 1238–1244 (2013). et al.
- Toward defining the autoimmune microbiome for type 1 diabetes. ISME J. 5, 82–91 (2011). et al.
- The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes. Cell Host Microbe 17, 260–273 (2015). et al.
- Periodontal disease and the oral microbiota in new-onset rheumatoid arthritis. Arthritis Rheum. 64, 3083–3094 (2012). et al.
- Human oral, gut, and plaque microbiota in patients with atherosclerosis. Proc. Natl Acad. Sci. USA 108 (suppl. 1), 4592–4598 (2011). et al.
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- Gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease. Circ. Res. 116, 448–455 (2015). et al.
- A genome-wide systems analysis reveals strong link between colorectal cancer and trimethylamine N-oxide (TMAO), a gut microbial metabolite of dietary meat and fat. BMC Genomics 16 (suppl. 7), S4 (2015). , &
- Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N. Engl. J. Med. 368, 1575–1584 (2013). et al.
- Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk. Cell 165, 111–124 (2016). et al.
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- Metagenomic analysis of the human distal gut microbiome. Science 312, 1355–1359 (2006).
This study provided the first metagenomic gene catalogue of the human gut.
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