scholarly journals Dietary fibre to reduce colon cancer risk in Alaska Native people: the Alaska FIRST randomised clinical trial protocol

BMJ Open ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. e047162
Author(s):  
Kathryn R Koller ◽  
Annette Wilson ◽  
Daniel P Normolle ◽  
Jeremy K Nicholson ◽  
Jia V Li ◽  
...  
Keyword(s):  
Cancer Risk ◽  
Gut Microbiota ◽  
Alaska Native ◽  
Dietary Fibre ◽  
Native People ◽  
Screening Colonoscopy ◽  
Secondary Outcome ◽  
Research Review ◽  
High Fibre ◽  
The Impact

IntroductionDiet, shown to impact colorectal cancer (CRC) risk, is a modifiable environmental factor. Fibre foods fermented by gut microbiota produce metabolites that not only provide food for the colonic epithelium but also exert regulatory effects on colonic mucosal inflammation and proliferation. We describe methods used in a double-blinded, randomised, controlled trial with Alaska Native (AN) people to determine if dietary fibre supplementation can substantially reduce CRC risk among people with the highest reported CRC incidence worldwide.Methods and analysesEligible patients undergoing routine screening colonoscopy consent to baseline assessments and specimen/data collection (blood, urine, stool, saliva, breath and colon mucosal biopsies) at the time of colonoscopy. Following an 8-week stabilisation period to re-establish normal gut microbiota post colonoscopy, study personnel randomise participants to either a high fibre supplement (resistant starch, n=30) or placebo (digestible starch, n=30) condition, repeating stool sample collection. During the 28-day supplement trial, each participant consumes their usual diet plus their supplement under direct observation. On day 29, participants undergo a flexible sigmoidoscopy to obtain mucosal biopsy samples to measure the effect of the supplement on inflammatory and proliferative biomarkers of cancer risk, with follow-up assessments and data/specimen collection similar to baseline. Secondary outcome measures include the impact of a high fibre supplement on the oral and colonic microbiome and biofluid metabolome.Ethics and disseminationApprovals were obtained from the Alaska Area and University of Pittsburgh Institutional Review Boards and Alaska Native Tribal Health Consortium and Southcentral Foundation research review bodies. A data safety monitoring board, material transfer agreements and weekly study team meetings provide regular oversight throughout the study. Study findings will first be shared with AN tribal leaders, health administrators, providers and community members. Peer-reviewed journal articles and conference presentations will be forthcoming once approved by tribal review bodies.Trial registration numberNCT03028831.

Abstract 14: An Anti-inflammatory Proton Sensing-receptor Contributes To Cardiovascular Protection Of Gut Microbiota-derived Metabolites

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Liang Xie ◽  
Rikeish R Muralitharan ◽  
Evany Dinakis ◽  
Michael E Nakai ◽  
Hamdi Jama ◽  
...  
Keyword(s):  
T Cell ◽  
Gut Microbiota ◽  
Dietary Fibre ◽  
Dietary Intervention ◽  
Immune Cell ◽  
Ang Ii ◽  
Direct Role ◽  
Cardiovascular Protection ◽  
Anti Inflammatory ◽  
The Impact

High fibre (HF) diet protects against hypertension via the production of acidic metabolites, e.g. short-chain fatty acids, by the gut microbiota. While these metabolites have a direct role in blood pressure (BP) regulation, their acidic nature may activate proton-sensing receptors, which have anti-inflammatory functions. G-protein coupled receptor 65 (GPR65) is a proton-sensing receptor activated around pH 6.5 and is critical for gut homeostasis. We hypothesized that GPR65 is involved in the cardiovascular protection by dietary fibre. We first measured cecal pH of C57BL/6 (WT) mice after a 7-day dietary intervention with either HF or low fibre (LF) diets (n=6/group). HF diet lowered cecal pH to a level where GPR65 is highly activated, compared to the LF diet (6.5±0.1 vs 7.6±0.1, P<0.001). The impact of pH and GPR65 on T cell production of IFNγ, a pro-inflammatory cytokine, in vitro was measured by flow cytometry. Acidic pH inhibited the production of IFNγ by CD8+ T cells (pH 6.5 vs pH 7.5, P<0.001). Cells lacking GPR65 had higher IFNγ at both pH (P<0.001). To determine if GPR65 is involved in BP regulation by dietary fibre, WT and GPR65 knockout ( Gpr65 -/- ) mice were implanted with minipumps containing angiotensin II (Ang II, 0.5mg/kg/day, 28 days, n=8-9/group) and fed with HF diet. BP, cardiorenal function and immune cell infiltration were measured. Gpr65 -/- mice had higher BP compared to WT mice after 2 weeks (mean arterial pressure ± SEM; WT 79.8±2.4 vs Gpr65 -/- 95.8±1.6mmHg, P<0.001) and 4 weeks of Ang II infusion (WT 92.3±2.4 vs Gpr65 -/- 99.5±1.3, P=0.062). Gpr65 -/- mice developed cardiac (P=0.035) and renal (P=0.025) hypertrophy, and impaired renal natriuretic (P=0.054) and diuretic (P=0.056) function compared to WT mice. This was accompanied by higher macrophage (P=0.009) and γδ T cell (P=0.014) infiltration in the kidneys. In conclusion, our data suggest that pH-sensing by GPR65 contributes to the protection against hypertension by dietary fibre via inflammatory mechanisms. This is a novel mechanism that contributes to BP regulation via the gut microbiota.

scholarly journals Association of dietary fibre intake and gut microbiota in adults

2018 ◽  
Vol 120 (9) ◽  
pp. 1014-1022 ◽  
Author(s):  
Daniel Lin ◽  
Brandilyn A. Peters ◽  
Charles Friedlander ◽  
Hal J. Freiman ◽  
James J. Goedert ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Risk ◽  
Gut Microbiota ◽  
Dietary Fibre ◽  
Meta Analysis ◽  
Microbiota Composition ◽  
Fibre Intake ◽  
Dietary Fibre Intake ◽  
The Relationship ◽  
Gut Microbiota Composition

AbstractIncreasing evidence indicates that gut microbiota may influence colorectal cancer risk. Diet, particularly fibre intake, may modify gut microbiota composition, which may affect cancer risk. We investigated the relationship between dietary fibre intake and gut microbiota in adults. Using 16S rRNA gene sequencing, we assessed gut microbiota in faecal samples from 151 adults in two independent study populations: National Cancer Institute (NCI), n 75, and New York University (NYU), n 76. We calculated energy-adjusted fibre intake based on FFQ. For each study population with adjustment for age, sex, race, BMI and smoking, we evaluated the relationship between fibre intake and gut microbiota community composition and taxon abundance. Total fibre intake was significantly associated with overall microbial community composition in NYU (P=0·008) but not in NCI (P=0·81). In a meta-analysis of both study populations, higher fibre intake tended to be associated with genera of class Clostridia, including higher abundance of SMB53 (fold change (FC)=1·04, P=0·04), Lachnospira (FC=1·03, P=0·05) and Faecalibacterium (FC=1·03, P=0·06), and lower abundance of Actinomyces (FC=0·95, P=0·002), Odoribacter (FC=0·95, P=0·03) and Oscillospira (FC=0·96, P=0·06). A species-level meta-analysis showed that higher fibre intake was marginally associated with greater abundance of Faecalibacterium prausnitzii (FC=1·03, P=0·07) and lower abundance of Eubacterium dolichum (FC=0·96, P=0·04) and Bacteroides uniformis (FC=0·97, P=0·05). Thus, dietary fibre intake may impact gut microbiota composition, particularly class Clostridia, and may favour putatively beneficial bacteria such as F. prausnitzii. These findings warrant further understanding of diet–microbiota relationships for future development of colorectal cancer prevention strategies.

scholarly journals Effect of Sequentially Fed High Protein, Hydrolysed Protein, and High Fibre Diets on The Faecal Microbiota of Healthy Dogs: A Cross-Over Study

2020 ◽  
Author(s):  
Lina Maria Martinez-Lopez ◽  
Amy Pepper ◽  
Rachel Pilla ◽  
Andrew Woodward ◽  
Jan Suchodolski ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Dietary Intervention ◽  
High Protein ◽  
Commercial Diet ◽  
High Fibre ◽  
Healthy Dogs ◽  
The Individual ◽  
Faecal Microbiome ◽  
The Impact ◽  
Protein Diets

Abstract Background Dietary content and environmental factors can shape the gut microbiota, and consequently, the way the gut microbiota metabolises fats, carbohydrates and proteins, affecting overall health of the host. We evaluated the impact of 3 diets (high protein, high fibre and hypoallergenic [hydrolysed protein]) diets on the gut microbiota of healthy dogs in a cross-over sequential study. Results We showed that diet can have a large effect on the gut microbiome in dogs, regardless of the order of feeding. High-protein (all meat) diets were characterised by an increase in bacteria belonging to the Fusobacteria and Bacteroidetes phyla, whereas a high-fibre commercial diet correlated with increases in Firmicutes and Actinobacteria phyla. However, the individual dog’s baseline microbiota had the most impact on the magnitude and nature of the changes in response to dietary intervention. Conclusion Our results suggest that the dog faecal microbiome is driven by protein and fibre composition, and targeted modification of these patterns could be useful in the modulation of the gut microbiota in different diseases.

The effects of carbohydrate structure on the composition and functionality of the human gut microbiota

2020 ◽  
Author(s):  
L Payling ◽  
K Fraser ◽  
SM Loveday ◽  
Ian Sims ◽  
N Roy ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Human Health ◽  
Food Processing ◽  
Dietary Fibre ◽  
Keystone Species ◽  
Hierarchical Structures ◽  
Microbial Composition ◽  
Food Structure ◽  
Interacting Networks ◽  
The Impact

© 2020 Elsevier Ltd Background: Human health depends on a population of microorganisms that inhabit the gut and contribute to homeostasis of the host, including nutrition, immunity and metabolism. Many of the organisms are interactive and mutually dependent, where the end-products for one organism become the fuel for another through substrate and metabolic cross-feeding. To optimise the gut microbiota using diet, the composition and functionality of the gut microbiota, including these interacting networks, must be understood. Microbial composition and functionality is affected by the structure of the energy input, which is primarily dietary fibre for the gut microbiota. The structure of dietary fibre has been reviewed by carbohydrate chemists, but knowledge of how dietary fibre structure affects the gut microbiota is limited. Scope and approach: The hierarchical structures of dietary fibre are reviewed, encompassing macrostructure, mesostructure and molecular structure, and how they are affected by food processing and digestion. These factors are considered in relation to their affects on microbial composition and functionality, to provide insight on the interactions between diet, the microbiota, and human health. Key findings and conclusions: Food processing and digestion affect food structure, primarily through the removal of some soluble fractions and increased solubilisation of insoluble fractions. The provision of insoluble carbohydrates to the colon appears important for the sustenance of ‘keystone’ species that play a crucial role in stabilising the gut community. Further work is needed at the microbial strain level to understand the impact of increasing fibre solubility. This should be done in studies using well-characterised carbohydrates that consider the impact of food processing and digestion.

Abstract MP37: Epigenetic Changes Following Maternal Gut Microbiota Improvement With Dietary Fibre Lead To Cardio-protection In The Offspring

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Hamdi Jama ◽  
Malathi I Dona ◽  
Evany Dinakis ◽  
Michael E Nakai ◽  
Madeleine Paterson ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Dietary Fibre ◽  
Maternal Diet ◽  
Regulatory Region ◽  
Left Ventricular ◽  
Epigenetic Changes ◽  
Ang Ii ◽  
Microbial Composition ◽  
Fibre Intake ◽  
High Fibre

Dietary fibre is fermented by the gut microbiota and protects against the development of cardiovascular disease (CVD) through the production of gut microbial metabolites. We hypothesised dietary fibre intake during pregnancy may prevent the development of CVD in the offspring via in utero epigenetic mechanisms. To investigate this, we fed C57BL/6J female mice diets high or low in resistant starches (‘high-fibre’ and ‘low-fibre’, respectively) during gestation. At 6-weeks of age, we performed single-cell RNA-sequencing in the offspring (n=8/group) or they were challenged with saline (sham) or angiotensin II (Ang II, 0.25mg/kg/day, n=18-23/group). Maternal diet resulted in a distinct gut microbial composition ( P =0.001). This was still evident in the adult offspring, with high-fibre offspring having a different gut microbial colonisation ( P =0.001), irrespective of sham/Ang II treatment. Maternal fibre intake significantly changed the cardiac cellular and molecular landscape and promoted differential gene signatures in the offspring. This included upregulation of genes associated with extracellular matrix production in the offspring from low-fibre mothers. When challenged with Ang II, low-fibre offspring developed increased cardiac hypertrophy ( P =0.034) and fibrosis ( P =0.01) compared to high-fibre offspring. This was accompanied with decreased ejection fraction ( P =0.001) and increased left ventricular posterior wall thickness ( P= 0.017). These changes were independent of blood pressure. High-fibre offspring had decreased expression of natriuretic peptides ( Nppa , P =0.03, Nppb , P =0.002) compared to low-fibre offspring. Chromatin-immunoprecipitation assay revealed decrease in H3-acetylation at the cis-regulatory region of Nppa gene in Ang II-treated high-fibre offspring (P=0.002), suggesting that maternal fibre intake influences the epigenetic changes of the Nppa gene in the offspring’s heart. Together, these data reveal maternal high-fibre intake leads to foetal epigenetic reprogramming, likely through maternal to foetal transfer of gut microbial-derived metabolites.

scholarly journals Exploring the impact of gut microbiota and diet on breast cancer risk and progression

2021 ◽  
Author(s):  
Nancy M. Y. Teng ◽  
Christopher A. Price ◽  
Alastair M. McKee ◽  
Lindsay J. Hall ◽  
Stephen D. Robinson
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Gut Microbiota ◽  
The Impact

Abstract 62: Dietary Fibre Attenuates Hypertension By Reducing Macrophage Infiltration Via Gut Microbiota-Derived Metabolite-Sensing Receptors

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Rikeish R Muralitharan ◽  
Evany Dinakis ◽  
Chudan Xu ◽  
Liang Xie ◽  
Hamdi Jama ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Dietary Fibre ◽  
Renal Fibrosis ◽  
Heart Function ◽  
Macrophage Infiltration ◽  
Chow Diet ◽  
Ang Ii ◽  
High Fibre Diet ◽  
Fibre Diet ◽  
High Fibre

High dietary fibre is fermented by the gut microbiota, resulting in the release of metabolites called short-chain fatty acids (SCFAs). Both fibre and SCFAs can reduce high blood pressure (BP) and its associated cardio-renal complications. However, the underlying mechanisms remain unclear. SCFAs can be detected by metabolite-sensing receptors GPR41 and GPR43, highly expressed by immune cells such as macrophages. We hypothesised that dietary fibre attenuates hypertension by modulating renal macrophage infiltration via metabolite-sensing receptors GPR41 and GPR43. To test this, we developed a novel GPR41/GPR43 double knockout (DKO) mice and characterised the cardiovascular and immune phenotype in both sham and angiotensin-II (Ang-II, 0.5mg/kg/day) treated DKO and wild-type (WT) mice (n=7-12 per group). WT Ang-II mice fed a high-fibre diet had significantly lower renal galectin-3 (p=0.0004), a macrophage marker, compared to WT Ang-II mice fed a low-fibre diet. Sham DKO mice on standard chow diet had no difference in BP or heart function but had higher kidney/tibia length index (p=0.049) and renal fibrosis levels compared to WT mice (p=0.004). Moreover, untreated DKO mice had higher numbers of renal macrophages compared to WT mice (p=0.002). Ang-II infusion of DKO mice resulted in higher BP (p<0.0001), renal fibrosis (p=0.007), and mortality (hazard ratio=5.6) compared to WT mice. In the gut, we found significant inflammatory changes, gut barrier integrity disruption, gut microbiota and metabolome changes (all p<0.05). We also found evidence of lipopolysaccharides (LPS) translocation from the gut into the circulation of DKO mice. In conclusion, we show that a high-fibre diet attenuates hypertension by modulating renal macrophages via the gut microbiota-derived metabolite-sensing GPR41 and GPR43 receptors. These receptors can be targeted as a novel treatment for hypertension.

scholarly journals Does geographical variation confound the relationship between host factors and the human gut microbiota: a population-based study in China

BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e038163
Author(s):  
Shan Sun ◽  
Huijun Wang ◽  
Matthew CB Tsilimigras ◽  
Annie Green Howard ◽  
Wei Sha ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Geographical Variation ◽  
Population Based ◽  
Host Factors ◽  
Secondary Outcome ◽  
Human Gut ◽  
Population Based Study ◽  
Human Gut Microbiota ◽  
Wide Range ◽  
The Impact

ObjectiveThe human gut microbiota plays important roles in human health but is also known to be highly diverse between populations from different regions. Yet most studies inadequately account for this regional diversity in their analyses. This study examines the extent to which geographical variation can act as a confounding variable for studies that associate the microbiota with human phenotypic variation.DesignPopulation-based study.SettingChina.Participants2164 participants from 15 province-level divisions in China.Primary and secondary outcome measuresWe analysed the impact of geographic location on associations between the human gut microbiota and 72 host factors representing a wide variety of environmental-level, household-level and individual-level factors.ResultsWhile the gut microbiota varied across a wide range of host factors including urbanisation, occupation and dietary variables, the geographic region (province/megacity) of the participants explained the largest proportion of the variance (17.9%). The estimated effect sizes for other host factors varied substantially by region with little evidence of a reproducible signal across different areas as measured by permutational multivariate analysis of variance and random forest models.ConclusionsOur results suggest that geographic variation is an essential factor that should be explicitly considered when generalising microbiota-based models to host phenotype across different populations.

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