Numerical ecology validates a biogeographical distribution and gender-based effect on mucosa-associated bacteria along the human colon

Cárcer, Daniel Aguirre de; Cuív, Páraic Ó; Wang, Tingtin; Kang, Seungha; Worthley, Daniel L.; Whitehall, Vicki; Gordon, Iain J.; McSweeney, Christopher S.; Leggett, Barbara A.; Morrison, Mark

doi:10.1038/ismej.2010.177

Cited by 80 publications

(44 citation statements)

References 58 publications

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“…The general diversity of the gut microbiome is matched by the observed high level of variance in its composition between individuals (Turnbaugh et al, 2009;Yatsunenko et al, 2012;Schloissnig et al, 2013). Similarly, significant latitudinal variation between surface-adherent and luminal microbial populations has been confirmed by both DNA fingerprinting method (Zoetendal et al, 2002) and polymerase chain reaction-based clone library sequencing, (Eckburg et al, 2005) and plenty of other studies found longitudinal variations of microbial components along the length of the intestinal tract based on cultivation approaches, (Moore and Holdeman, 1974;Hayashi et al, 2002) molecular fingerprinting methods, (Zoetendal et al, 2002;Hayashi et al, 2005;de Carcer et al, 2011) as well as polymerase chain reaction-based clone library sequencing analyses (Hayashi et al, 2002;Hold et al, 2002;Wang et al, 2003Wang et al, , 2005Eckburg et al, 2005;Frank et al, 2007). Despite a rather well-rounded view of the gut microbiome taken from many viewpoints, to date there has been no quantitative illustration or feasible explanations that help explain the observed longitudinal variations in the intestine, largely due to a dearth of large-scale data.…”

Section: Introductionmentioning

confidence: 72%

“…Along the length of the human intestinal tract, spatial heterogeneity of mucosa microbiota remains poorly elucidated, despite previously observed spatial variations of mucosa microbiota (Zoetendal et al, 2002;Eckburg et al, 2005;de Carcer et al, 2011;Hong et al, 2011;Nava et al, 2012). The results of this study allowed us to conclude that there are clear, significant spatial heterogeneities existing in the human intestinal mucosa microbiota within a single individual based on a quantitative Taylor's power law analyses, which is in accordance with classical phylogenetic beta-diversity metrics of mucosa-associated microbial community diversities across seven sampling sites.…”

Section: Discussionmentioning

confidence: 99%

“…This finding was consistent with two facets linked with human gut health or disease. The members of the Enterobacteriaceae were the most abundant in the distal regions of the intestine in health subjects (de Carcer et al, 2011). Otherwise, a large increase in Enterobacteriaceae was found potentially associated with the ileocecal form of Crohn's disease (CD) (Willing et al, 2009(Willing et al, , 2010.…”

Section: Discussionmentioning

confidence: 99%

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Spatial heterogeneity and co-occurrence patterns of human mucosal-associated intestinal microbiota

et al. 2013

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Human gut microbiota shows high inter-subject variations, but the actual spatial distribution and co-occurrence patterns of gut mucosa microbiota that occur within a healthy human instestinal tract remain poorly understood. In this study, we illustrated a model of this mucosa bacterial communities' biogeography, based on the largest data set so far, obtained via 454-pyrosequencing of bacterial 16S rDNAs associated with 77 matched biopsy tissue samples taken from terminal ileum, ileocecal valve, ascending colon, transverse colon, descending colon, sigmoid colon and rectum of 11 healthy adult subjects. Borrowing from macro-ecology, we used both Taylor's power law analysis and phylogeny-based beta-diversity metrics to uncover a highly heterogeneous distribution pattern of mucosa microbial inhabitants along the length of the intestinal tract. We then developed a spatial dispersion model with an R-squared value greater than 0.950 to map out the gut mucosa-associated flora's non-linear spatial distribution pattern for 51.60% of the 188 most abundant gut bacterial species. Furthermore, spatial co-occurring network analysis of mucosa microbial inhabitants together with occupancy (that is habitat generalists, specialists and opportunist) analyses implies that ecological relationships (both oppositional and symbiotic) between mucosa microbial inhabitants may be important contributors to the observed spatial heterogeneity of mucosa microbiota along the human intestine and may even potentially be associated with mutual cooperation within and functional stability of the gut ecosystem.

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Section: Introductionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Spatial heterogeneity and co-occurrence patterns of human mucosal-associated intestinal microbiota

et al. 2013

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“…91 In contrast, significant differences have been found in a number of studies between the ileum and colon, 221,224 and a proximal to distal gradient described between ileum and proximal to distal colon. 225,226 In both CD and UC no significant difference has been identified between the ileum and colon. 220,222,223 This observation has been confirmed in CD in a recent study using microarray 227 as well as a study which involved pyrosequencing on biopsies of nine twin pairs.…”

Section: Stability Along the Gastrointestinal (Gi) Tractmentioning

confidence: 92%

Characterization of the Gastrointestinal Microbiota in Health and Inflammatory Bowel Disease

Cruz

Prideaux

Wagner

et al. 2012

Inflammatory Bowel Diseases

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The enteric bacterial flora play a key role in maintaining health. Inflammatory bowel disease is associated with quantitative and qualitative alterations in the microbiota. Early characterization of the microbiota involved culture-dependent techniques. The advent of metagenomic techniques, however, allows for structural and functional characterization using culture-independent methods. Changes in diversity, together with quantitative alterations in specific bacterial species, have been identified. The functional significance of these changes, and their pathogenic role, remain to be elucidated.

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“…Constrained ordination methods, such as analysis with respect to instrumental variables, will also be carried out [59]. …”

Section: Methodsmentioning

confidence: 99%

SYNbiotics Easing Renal failure by improving Gut microbiologY (SYNERGY): a protocol of placebo-controlled randomised cross-over trial

et al. 2014

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BackgroundEmerging evidence suggests modulating the microbiota in the large bowel of patients with chronic kidney disease (CKD) through pre- and/probiotic supplementation may inhibit the development of key nephrovascular toxins. To date, quality intervention trials investigating this novel treatment in CKD are lacking. The aim of SYNERGY is to assess the effectiveness of synbiotics (co-administration of pre- and probiotics) as a potential treatment targeting the synthesis of uremic toxins, specifically, indoxyl sulphate (IS) and p-cresyl sulphate (PCS).Methods/designThirty-seven patients with moderate to severe CKD (Stage IV and V, pre-dialysis) will be recruited to a double-blind, placebo-controlled, randomised cross-over trial. Patients will be provided with synbiotic therapy or placebo for 6 weeks, with a 4 week washout before cross-over. The primary outcome is serum IS, total and free (unbound) concentrations, measured using ultra-performance liquid chromatography. Secondary outcomes include serum PCS, total and free (unbound) concentrations; cardiovascular risk, measured by serum lipopolysaccharides, serum trimethylamine-N-oxide (TMAO) and inflammation and oxidative stress markers; kidney damage, measured by 24 hour proteinuria and albuminuria, estimated glomerular filtration rate and renal tubule damage (urinary kidney injury molecule-1); patients’ self assessed quality of life; and gastrointestinal symptoms. In addition, the effects on the community structure of the stool microbiota will be explored in a subset of patients to validate the mechanistic rationale underpinning the synbiotic therapy.DiscussionIS and PCS are two novel uremic toxins implicated in both cardiovascular disease (CVD) and progression of CKD. Preliminary studies indicate that synbiotic therapy maybe a promising strategy when considering a targeted, tolerable and cost-efficient therapy for lowering serum IS and PCS concentrations. This trial will provide high quality ‘proof-of-concept’ data to elucidate both the efficacy of synbiotic therapy for lowering the toxins and whether reductions in serum IS and PCS translate into clinical benefits. Considering the potential of pre- and probiotics to not only shift toxin levels, but to also impede CVD and CKD progression, SYNERGY will provide vital insight into the effectiveness of this innocuous nutritional therapy.Trial RegistrationUniversal Trial Number: U1111-1142-4363. Australian New Zealand Clinical Trials Registry Number: ACTRN12613000493741, date registered: 2nd May 2013.

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Numerical ecology validates a biogeographical distribution and gender-based effect on mucosa-associated bacteria along the human colon

Cited by 80 publications

References 58 publications

Spatial heterogeneity and co-occurrence patterns of human mucosal-associated intestinal microbiota

Spatial heterogeneity and co-occurrence patterns of human mucosal-associated intestinal microbiota

Characterization of the Gastrointestinal Microbiota in Health and Inflammatory Bowel Disease

SYNbiotics Easing Renal failure by improving Gut microbiologY (SYNERGY): a protocol of placebo-controlled randomised cross-over trial

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