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 ◽  
...  

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.

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Hamdi Jama ◽  
Malathi I Dona ◽  
Evany Dinakis ◽  
Michael E Nakai ◽  
Madeleine Paterson ◽  
...  

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.


1992 ◽  
Vol 67 (1) ◽  
pp. 133-146 ◽  
Author(s):  
T. Gidenne

The use of specific methods other than gravimetric ones to analyse fibre permitted a more precise study of the degradation of cell wall (CW) in the digestive tract. Digesta flow and rate of passage measurements have not been assessed previously in rabbits to investigate fibre digestion and fibre effects simultaneously in the proximal and in the distal segments of the tract. The effect of the level of dietary fibre on ileal and overall digestibility and rate of passage were studied by comparing semi-purified diets containing only one source of CW (dehydrated lucerne (Medicago sativa) meal) given to adult female rabbits. The effect of fibre particle size and adaptation period were also investigated. Measurements of fibre composition using both colorimetric and gas-liquid chromatographic techniques, showed that large amounts of (CW) were degraded in the caecocolic segments. Increasing dietary fibre level reduced the rate of passage but fibre degradation was increased, at the same time a lower digestive efficiency for energy in the small intestine was found. A small quantity of CW was apparently degraded before the caecum, assuming that the water-soluble fraction of CW was essentially implicated. Grinding lucerne meal through a 1 mm instead of a 3 mm screen did not improve CW digestibility in spite of a longer rate of passage in the caeco-colic segments. Adaptation to a high-fibre diet resulted in an higher digestive volume for colon and caecum, related to an improved degradation of CW. Furthermore, digestive efficiency in the small intestine appeared higher for rabbits adapted to a high-fibre diet than that for rabbits initially fed on a low-fibre diet.


1987 ◽  
Vol 32 (4) ◽  
pp. 124-124 ◽  
Author(s):  
J.P. Lowell ◽  
V. Morrison ◽  
C.K.W. Lai ◽  
C.C. Khin ◽  
N.A.G. Mowat ◽  
...  

A high fibre diet is commonly used in Britain in the treatment of irritable bowel syndrome (IBS),1 although the efficacy of dietary fibre and of professional dietetic advice is not proven. This study was designed to assess whether the intake of dietary fibre could be related to the time spent receiving dietary advice.


1987 ◽  
Vol 72 (3) ◽  
pp. 343-350 ◽  
Author(s):  
Barrie M. Margetts ◽  
Lawrence J. Beilin ◽  
Robert Vandongen ◽  
Bruce K. Armstrong

1. Eighty-eight healthy omnivores with normal blood pressure participated in a randomized, controlled, cross-over trial of the effect on blood pressure of increasing dietary fibre intake. Subjects were randomly allocated to a control group eating a low fibre diet throughout, or to one of two experimental groups eating a high fibre diet for one of two 6-week experimental periods. Changes in body weight, other dietary constituents and lifestyle factors were avoided as far as possible. 2. Twenty-four hour diet records showed a substantial increase in dietary fibre when subjects were on the high fibre diet. 3. There was no consistent effect of change in dietary fibre intake on group mean systoloic or diastolic blood pressures. Adjusting blood pressures for changes in other dietary components, plasma lipids, electrolytes, body weight and other lifestyle variables did not alter this result. 4. These findings do not support the hypothesis that the blood pressure lowering effect of a vegetarian diet is solely due to an increase in fibre intake.


1991 ◽  
Vol 4 (3) ◽  
pp. 155-164 ◽  
Author(s):  
J. P. Lambert ◽  
V. Morrison ◽  
P. W. Brunt ◽  
N. A. G. Mowat ◽  
M. A. Eastwood ◽  
...  

1996 ◽  
Vol 75 (3) ◽  
pp. 365-378 ◽  
Author(s):  
Henry Jørgensen ◽  
Xin-Quan Zhao ◽  
Bjørn O. Eggum

AbstractThe present study was undertaken to provide detailed information about the effect of dietary fibre (DF)level on the development of the digestive tract, on nutrient digestibility and on energy and protein metabolism of pigs housed in low (13°) or high (23°) thermal environments. Low- and high-fibre diets (59 v. 268 g DF/kg DM) were studied in three balance periods with fistulated pigs in the weight range 45-120 kg. Heat production was measured using open-circuit respiration chambers. Pea fibre and pectin were used to adjust theDF level in the high-fibre diet. Per kg empty body weight the stomach, caecum and colon and the length of colon were significantly greater in pigs consuming the high-fibre diet than in those on the low-fibre diet. Pigs kept at low temperature had significantly heavier caecums than those kept at the high temperature. Digestibilities of protein, DM and energy were lowest for the high-fibre diet. Only minor amounts of NSP and its constituent sugars were degraded anterior to the ileum, whereas in the hind-gut the fermentation of the total NSP fraction was high, being 0·77 for the high-fibre diet and 0·59 for the low-fibre diet. Feeding the high-fibre diet increased the flow of digesta through the terminal ileum 5-6-fold and an extra 460 g organic matter was fermented daily in the hind-gut compared with pigs fed on the low-fibre diet. The amount of retained energy as a proportion of metabolizable energy decreased in relation to the amount of energy fermented in the hind-gut. Based on the present data it was estimated that the relative value of energy derived from hind-gut fermentation was 0·73 in comparison with energy enzymically digested in the small intestine. There was negligible effect of the temperature –fibre interaction on energy metabolism. However, it could be calculated that the decrease in temperature from 23° to 13° was associated with an increase in heat production by 2.9 MJ/pig per d.


BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Chee Kin Then ◽  
Salome Paillas ◽  
Xuedan Wang ◽  
Alix Hampson ◽  
Anne E. Kiltie

2005 ◽  
Vol 11 (2) ◽  
pp. 136-145
Author(s):  
Jo Paddison ◽  
Hemi Heta ◽  
Ross Flett

Understanding the distribution of Mãori across stages of health behaviour change (precontemplation, contemplation, preparation, action, maintenance) may inform the development of public health programs. In a replication and extension of a study by Nigg et al. (1999) we described the distribution of 73 Mãori male questionnaire respondents (age 18 to 59 years) across these stages for 8 healthy behaviours (avoiding dietary fat, eating fibre, reducing weight, regularly exercising, reducing stress, reducing sun exposure, using sunblock, and conducting cancer self-examinations). Respondents were also asked to rate their general health, health worries, and health locus of control. Evidence found of a continuum of change for ‘ignoring’, to ‘thinking about1 to ‘performing’ healthy behaviour provides moderate support for the idea that behaviour change is not an all-or-nothing event. There were no significant age effects. Respondents who rated their health more positively were more likely to report using sunblock, exercising regularly, and eating a high fibre diet. Respondents who felt they had more control over their health were more likely to eat a diet high in fibre. Eating a high fibre diet, exercising and managing stress were most strongly associated with the other health behaviours which may illustrate the concept of gateway behaviours proposed by Nigg et al. (1999).


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