Mechanistic Investigations on the influence of chickpea (Cicer arietinum L.) on obesity-associated inflammation
Final Report Abstract
Obesity-associated diseases are a major public health burden all over the world. A low grade systemic inflammation plays a crucial part in the development of these diseases. In the obese state increased gut permeability leads to higher levels of bacterial LPS in the circulation, which stimulates secretion of proinflammatory mediators. Furthermore influx of proinflammatory immune cells into adipose tissue, especially macrophages, has been observed in obesity. Both mechanisms contribute to the obesityassociated inflammation. Moreover an increased microbial energy harvest from food has been reported in obesity, thus indicating the involvement of gut microbiota in weight gain. Due to their high content of fiber and phytochemicals, pulses are amongst the foods of interest for nutritional strategies against obesity. It is hypothesized that they could change the gut microenvironment (gut microbiota composition and epithelial barrier function) and could reduce adipose tissue associated inflammation. In contrast to the original plans for this project, the pulse of interest was switched from chickpea to lentils. Before this project, nothing was known about the effective supplementation dose for lentils. Thus a doseresponse study in healthy mice was conducted, for which C57Bl/6 mice were fed 0 %, 5 %, 10 % or 20 % of lentils for three weeks. DNA was extracted from cecum content and feces and microbiota composition analysis revealed an increased α-diversity in all lentil groups in feces, but not cecum. Furthermore, abundance of short-chain fatty acid (SCFA) producing bacteria, namely Prevotella and a decrease in abundance for Bacteroides, Parabacteroides and Mucispirillum was observed. Fecal SCFA concentrations were only increased in the 20 % lentil group, but not the 5 % and 10 % groups. The lentil diets had no effect on proliferation, crypt length and number of goblet cells per crypt. As the 20 % lentil diet led to the most pronounced changes, 20 % lentils were used as supplementation level for the other studies. To investigate the influence of lentils on obesity, C57Bl/6 mice were fed with high fat diets (HFD) containing 45 % kcal or 60 % kcal fat or low fat control diets, with or without 20 % lentils. Lentil diets did not affect energy intake or body weight. Addition of lentils to the 60 % and 45 % HFD attenuated the decrease in αdiversity. In contrast to what has been described in the literature, the abundance of the phyla Firmicutes and Bacteroidetes was not affected by the different HFD. As seen in the dose-response study, the abundance of the genus Prevotella was increased by lentils, independent of the fat content. However, an increase in cecal SCFA concentration after lentil consumption was only observed on the 45 % fat level. Serum concentrations of LPS-binding protein (LBP), a marker for gut permeability, were increased in the HFD groups, but lentils had no effect. Serum concentration of the proinflammatory adipokines leptin and resistin were higher in the HFD groups. For the 45 % fat level lentils further increased leptin concentrations. As the obesity study was conducted very late in the project, analyses are still ongoing. To further assess the impact of lentils on gut health, a colitis study was conducted using a dextran sulfate sodium (DSS) model. Before induction of colitis with DSS, C57Bl/6 mice were pre-fed with lentils for the weeks. Three days after the end of DSS treatment, mice that were pre-fed with lentils had a lower disease activity index, decreased histological damage and lower serum LBP concentrations. The effects were only observed three days after DSS treatment, but not right at the end of DSS treatment and eight days after DSS treatment, thus indicating an earlier onset of recovery in the lentil pre-fed mice. In summary the results of the studies conducted during this project, indicated that a supplementation of diet with 20 % lentils can induce gut health promoting effects, probably through mechanisms involving the gut microbiota and SCFA. For a final assessment of the influence of lentils on obesity more data are needed.
Publications
- Chickpea-supplemented diet alters the gut microbiome and enhances gut barrier integrity in C57Bl/6 male mice. Journal of Functional Foods (2017)
JM. Monk, D. Lepp, W. Wu, D. Graf, LH. McGillis, A. Hussain, C. Carey, LE.. Robinson, R. Liu, R. Tsao, Y. Brummer, SM. Tosh, KA. Power
(See online at https://doi.org/10.1016/j.jff.2017.02.002) - Diets supplemented with lentils influence the gut microbiota community structure and activity and modulate the integrity of the gut barrier in male C57Bl/6 mice. DGE Kongress March 2017
D. Graf, D. Lepp, JM. Monk, W. Wu, C. Carey, LE. Robinson, KA. Power
- The effects of diets supplemented with lentils on the gut microbiome, gut barrier integrity, and DSS-induced colitis severity in male C57Bl/6 mice. Conference of the Canadian Nutrition Society “Advances in Nutrition Gut Health and Microbiome” January 2017
D. Graf, D. Lepp, JM. Monk, W. Wu, C. Carey, K. Roberton, LE. Robinson, KA. Power
