Ref GIT

[Jo Bowyer]

For consideration in assessment treatment and management of infantile colic, IBS, fibromyalgia and rheumatological conditions where there is gut involvement.

The Role of Visceral Afferents in Disease
http://www.ncbi.nlm.nih.gov/books/NBK57266/

https://www.somasimple.com/forums/sh...h%3A+Mouse+Man.

https://www.somasimple.com/forums/sh...81&postcount=1

British Osteopaths should be mindful of the recent ASA review and guidance from GOsC

[Jo Bowyer]

Microbiome (....how does your garden grow?)

[Sharkey, Savidge 2014] Reprint of: Role of enteric neurotransmission in host defense and protection of the gastrointestinal tract
https://www.somasimple.com/forums/sh...9&postcount=13

The human microbiome: Me, myself, us
https://www.somasimple.com/forums/sh...92&postcount=1

Carl Zimmer, the microbiome
https://www.somasimple.com/forums/sh...ght=microbiome

[Jo Bowyer]

Use of the Analysis of the Volatile Faecal Metabolome in Screening for Colorectal Cancer

http://journals.plos.org/plosone/art...l.pone.0130301

Abstract

Diagnosis of colorectal cancer is an invasive and expensive colonoscopy, which is usually carried out after a positive screening test. Unfortunately, existing screening tests lack specificity and sensitivity, hence many unnecessary colonoscopies are performed. Here we report on a potential new screening test for colorectal cancer based on the analysis of volatile organic compounds (VOCs) in the headspace of faecal samples. Faecal samples were obtained from subjects who had a positive faecal occult blood sample (FOBT). Subjects subsequently had colonoscopies performed to classify them into low risk (non-cancer) and high risk (colorectal cancer) groups. Volatile organic compounds were analysed by selected ion flow tube mass spectrometry (SIFT-MS) and then data were analysed using both univariate and multivariate statistical methods. Ions most likely from hydrogen sulphide, dimethyl sulphide and dimethyl disulphide are statistically significantly higher in samples from high risk rather than low risk subjects. Results using multivariate methods show that the test gives a correct classification of 75% with 78% specificity and 72% sensitivity on FOBT positive samples, offering a potentially effective alternative to FOBT.

This post may seem a bit spurious but it is relevent to gas emitted by the microbiome. I suspect that in the future rheumatologists will take a greater interest. One I worked with in the '80s was often called in for second opinion by GI physicians. I have several long term patients (15 years +) whose rheumatological issues were thought to have started with bacterial food poisoning.



Leveraging sequence-based faecal microbial community survey data to identify a composite biomarker for colorectal cancer

Abstract

Objective Colorectal cancer (CRC) is the second leading cause of cancer-associated mortality in the USA. The faecal microbiome may provide non-invasive biomarkers of CRC and indicate transition in the adenoma–carcinoma sequence. Re-analysing raw sequence and metadata from several studies uniformly, we sought to identify a composite and generalisable microbial marker for CRC.

Design Raw 16S rRNA gene sequence data sets from nine studies were processed with two pipelines, (1) QIIME closed reference (QIIME-CR) or (2) a strain-specific method herein termed SS-UP (Strain Select, UPARSE bioinformatics pipeline). A total of 509 samples (79 colorectal adenoma, 195 CRC and 235 controls) were analysed. Differential abundance, meta-analysis random effects regression and machine learning analyses were carried out to determine the consistency and diagnostic capabilities of potential microbial biomarkers.

Results Definitive taxa, including Parvimonas micra ATCC 33270, Streptococcus anginosus and yet-to-be-cultured members of Proteobacteria, were frequently and significantly increased in stools from patients with CRC compared with controls across studies and had high discriminatory capacity in diagnostic classification. Microbiome-based CRC versus control classification produced an area under receiver operator characteristic (AUROC) curve of 76.6% in QIIME-CR and 80.3% in SS-UP. Combining clinical and microbiome markers gave a diagnostic AUROC of 83.3% for QIIME-CR and 91.3% for SS-UP.

Conclusions Despite technological differences across studies and methods, key microbial markers emerged as important in classifying CRC cases and such could be used in a universal diagnostic for the disease. The choice of bioinformatics pipeline influenced accuracy of classification. Strain-resolved microbial markers might prove crucial in providing a microbial diagnostic for CRC.

Update 20/04/2017

[Jo Bowyer]

Digested wheat gluten inhibits binding between leptin and its receptor

http://www.biomedcentral.com/1471-2091/16/3

Abstract

Background
Leptin resistance is considered a primary risk factor for obesity. It has been hypothesized that dietary cereal grain protein could cause leptin resistance by preventing leptin from binding to its receptor. Non-degraded dietary wheat protein has been found in human serum at a mean level of 41 ng/mL. Here, we report our findings from testing whether enzymatically digested gluten from wheat prevents leptin from binding to the leptin receptor in vitro.

Gluten from wheat was digested with pepsin and trypsin under physiological conditions. Pepsin and trypsin activity was removed from the gluten digest with a 10 kDa spin-filter or by heat treatment at 100°C for 30 min. Binding to the leptin receptor of leptin mixed with gluten digest at a series of concentrations was measured using surface plasmon resonance technology.

Results
Binding of the gluten digest to the leptin receptor was not detected. Spin-filtered gluten digest inhibited binding of leptin to the leptin receptor, with 50% inhibition at a gluten digest concentration of ~10 ng/mL. Heat-treated gluten digest did not inhibit leptin binding.

Conclusions
Digested wheat gluten inhibits binding of leptin to the leptin receptor, with half-maximal inhibition at 10 ng/mL. The inhibition is significant at clinically relevant concentrations and could therefore serve as a novel pathway to investigate to understand the molecular basis of leptin resistance, obesity and associated disorders.

Keywords: Gluten; Leptin; Leptin resistance; Obesity
Background

[Jo Bowyer]

The Evolution of Stomach Acidity and Its Relevance to the Human Microbiome

http://journals.plos.org/plosone/art...l.pone.0134116

Abstract

Gastric acidity is likely a key factor shaping the diversity and composition of microbial communities found in the vertebrate gut. We conducted a systematic review to test the hypothesis that a key role of the vertebrate stomach is to maintain the gut microbial community by filtering out novel microbial taxa before they pass into the intestines. We propose that species feeding either on carrion or on organisms that are close phylogenetic relatives should require the most restrictive filter (measured as high stomach acidity) as protection from foreign microbes. Conversely, species feeding on a lower trophic level or on food that is distantly related to them (e.g. herbivores) should require the least restrictive filter, as the risk of pathogen exposure is lower. Comparisons of stomach acidity across trophic groups in mammal and bird taxa show that scavengers and carnivores have significantly higher stomach acidities compared to herbivores or carnivores feeding on phylogenetically distant prey such as insects or fish. In addition, we find when stomach acidity varies within species either naturally (with age) or in treatments such as bariatric surgery, the effects on gut bacterial pathogens and communities are in line with our hypothesis that the stomach acts as an ecological filter. Together these results highlight the importance of including measurements of gastric pH when investigating gut microbial dynamics within and across species.

[Jo Bowyer]

Association between anti-Porphyromonas gingivalis or anti-α-enolase antibody and severity of periodontitis or rheumatoid arthritis (RA) disease activity in RA

http://www.biomedcentral.com/1471-2474/16/190

Abstract

Background
Periodontitis (PD) has been reported to be associated with rheumatoid arthritis (RA). Porphyromonas gingivalis (P. gingivalis) is a gram-negative anaerobic bacterium that is recognized as one of the major pathogenic organisms in PD and is the only bacterium known to express peptidylarginine deiminase (PAD). Antibody against human α-enolase (ENO1) is one of the autoantibodies in RA. ENO1 is a highly conserved protein, and could be a candidate molecule for molecular mimicry between bacterial and human proteins. In the present study, we measured serum antibody against P. gingivalis and human ENO1 in patients with RA and investigated their association with the severity of PD or disease activity of RA.

Methods
Two hundred, forty-eight patients with RA and 85 age- and sex-matched healthy controls were evaluated by rheumatologic and periodontal examinations. The serum levels of anti-P. gingivalis and anti-ENO1 antibodies were measured by an enzyme-linked immunosorbent assay (ELISA).

Results
Patients with RA had significantly higher levels of anti-P. gingivalis and anti-ENO1 antibody titers than the controls (p = 0.002 and 0.0001, respectively). Anti-P. gingivalis antibody titers significantly correlated with anti-ENO1 antibody titers in RA patients (r = 0.30, p < 0.0001). There were significant correlations between anti-P. gingivalis antibody titers and the gingival index (GI), probing pocket depth (PPD), bleeding on probing (BOP) and clinical attachment level (CAL) (p = 0.038, 0.004, 0.004 and 0.002, respectively) in RA. Anti-P. gingivalis antibody titers were not correlated with disease activity score 28 (DAS28) or anti-CCP titer. However, anti-ENO1 antibody titers were significantly correlated not only with the periodontal indices, such as PPD, BOP, and CAL (p = 0.013, 0.023 and 0.017, respectively), but also RA clinical characteristics, such as DAS28, anti-CCP titer, and ESR (p = 0.009, 0.015 and 0.001, respectively).

Conclusion
Anti-P. gingivalis and anti-ENO1 antibody titers were correlated with the severity of PD in RA. Anti-ENO1 antibody titers, but not anti-P. gingivalis antibody titers, were further associated with RA disease activity.

[Jo Bowyer]

Emerging importance of holobionts in evolution and in probiotics

Abstract

The existence of microbe free animals or plants in nature is virtually impossible as they and plants have a certain degree of symbiotic association with microbes. This symbiotic association leads to the formation of holobiont (host and its symbionts). This mutual coexistence is not merely at the physical or chemical level but also at the
genetic level leading to the emergence of the concept of hologenome (gene pool of host and its associated symbionts). The abundance of symbionts with the associated gene diversity contributes to the fitness of the holobiont under varying environmental conditions. The hologenome theory of evolution considers the dynamic holobiont as a single unit for natural selection and provides a more accommodating view of evolution blending Darwinism and Lamarkism. Additionally, holobionts are providing scientific basis to our understanding of the
growing importance of probiotics in human health and in disease management.

Keywords: Evolution, Symbiont, Hologenome, Holobiont, Probiotics

[Jo Bowyer]

Being human is a gut feeling

https://www.somasimple.com/forums/sh...&postcount=182

[Jo Bowyer]

Phylogenetic and Metabolic Tracking of Gut Microbiota during Perinatal Development

http://journals.plos.org/plosone/art...l.pone.0137347

Abstract

The colonization and development of gut microbiota immediately after birth is highly variable and depends on several factors, such as delivery mode and modality of feeding during the first months of life. A cohort of 31 mother and neonate pairs, including 25 at-term caesarean (CS) and 6 vaginally (V) delivered neonates (DNs), were included in this study and 121 meconium/faecal samples were collected at days 1 through 30 following birth. Operational taxonomic units (OTUs) were assessed in 69 stool samples by phylogenetic microarray HITChip and inter- and intra-individual distributions were established by inter-OTUs correlation matrices and OTUs co-occurrence or co-exclusion networks. 1H-NMR metabolites were determined in 70 stool samples, PCA analysis was performed on 55 CS DNs samples, and metabolome/OTUs co-correlations were assessed in 45 CS samples, providing an integrated map of the early microbiota OTUs-metabolome. A microbiota “core” of OTUs was identified that was independent of delivery mode and lactation stage, suggesting highly specialized communities that act as seminal colonizers of microbial networks. Correlations among OTUs, metabolites, and OTUs-metabolites revealed metabolic profiles associated with early microbial ecological dynamics, maturation of milk components, and host physiology.

Introduction

The microbial colonization from birth to adulthood of a healthy human gut is characterized by a dynamic sequence of events that plays a critical role in promoting intestinal homeostasis and stimulating normal immune system (IS) development and response. These functions provide an array of beneficial advantages to the human host, including nutrient processing and metabolism, energy storage, and protection against pathogen colonization [1–9]. The gastrointestinal (GI) microbiota is composed by autochthonous (i.e., indigenous) and allochthonous (i.e., transient) microbes [2]. Most pathogens are allochthonous microorganisms. However, some potential pathogens can be considered autochthonous and normally reside unperturbed within the colonic host microbiota until the ecosystem is perturbed and homeostasis is disturbed. Abnormalities in gut microbiome composition and associated changes in IS tolerance have been increasingly linked with early-onset childhood diseases [10]. Pioneering gut constituents and their impact on metabolic pathways in early infancy may have both short- and long-term health-related implications in humans [4,11–14]. However, while gut microbiota in neonates is characterized by high inter-individual variability and uneven distribution of taxa throughout this developmental stage [15–18], it remains unclear what role this variation has in the function and the progression of the microbial community in the very early stages of life [18].

Several studies have shown that both differential exposure of neonates to maternal vaginal, faecal, and skin microbiota due to delivery mode (i.e., vaginal or C-section) and modality of feeding during the first months of life (i.e., breastfeeding and/or formula-feeding) accounts for the richness, diversity, and composition of the gut microbial community [1,18–25]. However, little is known regarding the bacterial composition of meconium through to faeces during the first weeks of life [16,26,27]. Studies on meconium bacterial diversity, highlighting the succession of gut microbiota communities, could assist in developing strategies for selecting health-promoting microbiota for preservation throughout the lifespan of the host [28,29]. These microbial communities could be considered targets for therapeutic intervention in several chronic childhood diseases [30–33].

Gut microbiota contributes to the host metabolism through numerous mechanisms, including increased energy harvested from the diet, modulation of lipid metabolism, altered endocrine function, and increased inflammatory response [34,35]. Microbiota metabolic functions are mainly based on the fermentation of available substrates that have escaped digestion in the upper GI tract and flaking enterocytes [36]. In the early days of life, the major sources of carbohydrates for infant gut microbiota are human milk oligosaccharides (HMOSs), endogenous glycans (mucines), undigested monosaccharides and lactose, and, in the case of formula feeding, prebiotics [37]. Complex carbohydrates are principally degraded by Bifidobacterium, Lactobacillus, and Bacteroides (HMOSs and mucin degraders) into small sugars (e.g., lactose), which are further metabolized by glycolytic microbes, including lactate producing bacteria such as Streptococcus, Staphylococcus, Enterococcus, and Enterobacteria [38].

Thus, a major challenge in the understanding of host–microbiome metabolic interactions, notably the role of gut microbiota in early life, is how it affects an individual’s health programming. Metabolomics may play a pivotal role in understanding the mechanism of infant intestinal development. Such approaches involve the identification and quantification of hundreds of small metabolites from bodily fluids and tissues, providing functional insights into the complex interactions between gut microbes and the host [39]. While several NMR-based metabolomic studies on human adult stool have been performed to evaluate the influence of diet on gut microbiota or the association of dysbiosis with intestinal inflammatory diseases [40–42], metabolomic investigations into the meconium or stool from infants are quite limited [43,44].

[Jo Bowyer]

The Gut Microbiome Contributes to a Substantial Proportion of the Variation in Blood Lipids

http://circres.ahajournals.org/conte...06807.abstract

Abstract

Rationale: Evidence suggests the gut microbiome is involved in the development of cardiovascular disease (CVD), with the host-microbe interaction regulating immune and metabolic pathways. However, there was no firm evidence for associations between microbiota and metabolic risk factors for CVD from large-scale studies in humans. In particular, there was no strong evidence for association between CVD and aberrant blood lipid levels

Objective: To identify intestinal bacteria taxa, whose proportions correlate with body mass index (BMI) and lipid levels, and to determine whether lipid variance can be explained by microbiota relative to age, gender and host genetics.

Methods and Results: We studied 893 subjects from the LifeLines-DEEP population cohort. After correcting for age and gender, we identified 34 bacterial taxa associated to BMI and blood lipids; most are novel associations. Cross-validation analysis revealed that microbiota explain 4.5% of the variance in BMI, 6% in triglycerides, and 4% in high-density lipoproteins (HDL), independent of age, gender and genetic risk factors. A novel risk model including the gut microbiome explained up to 25.9% of HDL variance, significantly outperforming the risk model without microbiome. Strikingly, the microbiome had little effect on low-density lipoproteins or total cholesterol.

Conclusions: Our studies suggest that the gut microbiome may play an important role in the variation in BMI and blood lipid levels, independent of age, gender and host genetics. Our findings support the potential of therapies altering the gut microbiome to control body mass, triglycerides and HDL.

[Jo Bowyer]

Quantifying Diet-Induced Metabolic Changes of the Human Gut Microbiome

http://www.cell.com/cell-metabolism/...131(15)00330-7

Highlights
•Community And Systems-level INteractive Optimization toolbox
•Modeling the effect of diet and gene richness on the gut microbiota
•Revealing altered amino acid and SCFA levels after diet interventions
Summary
The human gut microbiome is known to be associated with various human disorders, but a major challenge is to go beyond association studies and elucidate causalities. Mathematical modeling of the human gut microbiome at a genome scale is a useful tool to decipher microbe-microbe, diet-microbe and microbe-host interactions. Here, we describe the CASINO (Community And Systems-level INteractive Optimization) toolbox, a comprehensive computational platform for analysis of microbial communities through metabolic modeling. We first validated the toolbox by simulating and testing the performance of single bacteria and whole communities in vitro. Focusing on metabolic interactions between the diet, gut microbiota, and host metabolism, we demonstrated the predictive power of the toolbox in a diet-intervention study of 45 obese and overweight individuals and validated our predictions by fecal and blood metabolomics data. Thus, modeling could quantitatively describe altered fecal and serum amino acid levels in response to diet intervention.

[Jo Bowyer]

A Metagenomic Investigation of the Duodenal Microbiota Reveals Links with Obesity

http://journals.plos.org/plosone/art...l.pone.0137784

Abstract

Background

Few studies have tested the small intestine microbiota in humans, where most nutrient digestion and absorption occur. Here, our objective was to examine the duodenal microbiota between obese and normal volunteers using metagenomic techniques.

Methodology/Principal Findings

We tested duodenal samples from five obese and five normal volunteers using 16S rDNA V6 pyrosequencing and Illumina MiSeq deep sequencing. The predominant phyla of the duodenal microbiota were Firmicutes and Actinobacteria, whereas Bacteroidetes were absent. Obese individuals had a significant increase in anaerobic genera (p < 0.001) and a higher abundance of genes encoding Acyl-CoA dehydrogenase (p = 0.0018) compared to the control group. Obese individuals also had a reduced abundance of genes encoding sucrose phosphorylase (p = 0.015) and 1,4-alpha-glucan branching enzyme (p = 0.05). Normal weight people had significantly increased FabK (p = 0.027), and the glycerophospholipid metabolism pathway revealed the presence of phospholipase A1 only in the control group (p = 0.05).

Conclusions/Significance

The duodenal microbiota of obese individuals exhibit alterations in the fatty acid and sucrose breakdown pathways, probably induced by diet imbalance.

In conclusion, the low bacterial concentration and particular taxonomic composition of the duodenojejunal microbiota makes the evaluation of its variation by stool sample analysis extremely difficult. To the best of our knowledge, this is the first time that human duodenal samples have been analyzed by metagenomic techniques, and we found that the duodenal microbiota of obese individuals shows an increased capacity to degrade fatty acids, whereas the flora of control individuals shows an increased capacity to store fatty acids. Because the concentration of living bacteria is much higher in fermented products used as probiotics than in the duodenal flora (109 vs 105 microbes per mL, respectively), the impact of probiotics is probably more important on the duodenal than on the distal gut microbiota.

Altering gut bacteria pathways may stimulate fat tissue to prevent obesity


https://www.sciencedaily.com/release...0630124420.htm

A biological link has been discovered between gut bacteria metabolism and obesity. A research team showed that blocking a specific intestinal microbial pathway can prevent obesity and insulin resistance, as well as cause fat tissue to become more metabolically active.

The research team, led by J. Mark Brown, Ph.D., of Cleveland Clinic's Lerner Research Institute, studied the metabolic pathway that creates trimethylamine oxide (TMAO), a chemical produced by gut bacteria during digestion of key nutrients -- choline, lecithin and carnitine -- found abundantly in animal products, such as red meat, processed meats, egg yolks and liver.

Update 05/07/2017

[Jo Bowyer]

Viruses flourish in guts of healthy babies

http://www.sciencedaily.com/releases...0914152722.htm

The study, published online Sept. 14 in Nature Medicine, reports data from eight healthy infants and is one of the first surveys of viruses that reside in the intestine. The investigators analyzed stool samples to track how the babies' bacterial gut microbiomes and viromes changed over the first two years of life.

The picture that emerged may be worthy of a wildlife documentary: It includes the discovery of viral strains new to science and suggests a dynamic ecosystem of interacting organisms, including predators and their prey.

"We are just beginning to understand the interplay between all the different types of life within our gut," said senior author Lori R. Holtz, MD, assistant professor of pediatrics. "They are not stand-alone communities. We also are seeing that the environment of the infant gut is extremely dynamic, which differs from the relative stability that has been shown in adults."

[Jo Bowyer]

Plum good health benefits

http://today.agrilife.org/2015/09/24...alth-benefits/

“The hypothesis we tested in this experiment was that consumption of dried plums would promote retention of beneficial microbiota and patterns of microbial metabolism throughout the colon. If it did this, then it might also help reduce the risk of colon cancer.”

“The microbiota are involved in the health of the host organism through physical interactions and, indirectly, through their metabolism,” said Derek Seidel, a doctoral graduate student and research assistant for Turner who assisted in the study. “The rats were fed a control diet or a diet containing dried plums, and both diets were matched for total calories and macronutrient composition so that the effect due to diet would be attributed to compounds uniquely found in the dried plums.”

The intestinal contents and tissues from different segments of the colon were examined. Results showed that the dried plum diet increased Bacteroidetes and reduced Firmicutes – the two major phyla of bacteria in the gut – in the distal colon without affecting the proportions found in the proximal colon. However, animals consuming the control diet had a lower proportion of Bacteroidetes and increased Firmicutes in the distal colon.

Another observation made was rats consuming dried plums had significantly reduced numbers of aberrant crypts, aberrant crypt foci and high-multiplicity aberrant crypt foci compared to control rats.

“These aberrant crypt foci are one of the earliest observable precancerous lesions and are often considered to be a strong indicator for cancer development,” Seidel said.

[Diane]

Dried plums = prunes, right?