Modulation of Gut Microbiota of Overweight Mice by Agavins and Their Association with Body Weight Loss

Alicia Huazano-García, Hakdong Shin, Mercedes G López, Alicia Huazano-García, Hakdong Shin, Mercedes G López

Abstract

Agavins consumption has led to accelerated body weight loss in mice. We investigated the changes on cecal microbiota and short-chain fatty acids (SCFA) associated with body weight loss in overweight mice. Firstly, mice were fed with standard (ST5) or high-fat (HF5) diet for five weeks. Secondly, overweight mice were shifted to standard diet alone (HF-ST10) or supplemented with agavins (HF-ST + A10) or oligofructose (HF-ST + O10), for five more weeks. Cecal contents were collected before and after supplementation to determine microbiota and SCFA concentrations. At the end of first phase, HF5 mice showed a significant increase of body weight, which was associated with reduction of cecal microbiota diversity (PD whole tree; non-parametric t test, p < 0.05), increased Firmicutes/Bacteroidetes ratio and reduced SCFA concentrations (t test, p < 0.05). After diet shifting, HF-ST10 normalized its microbiota, increased its diversity, and SCFA levels, whereas agavins (HF-ST + A10) or oligofructose (HF-ST + O10) led to partial microbiota restoration, with normalization of the Firmicutes/Bacteroides ratio, as well as higher SCFA levels (p < 0.1). Moreover, agavins noticeably enriched Klebsiella and Citrobacter (LDA > 3.0); this enrichment has not been reported previously under a prebiotic treatment. In conclusion, agavins or oligofructose modulated cecal microbiota composition, reduced the extent of diversity, and increased SCFA. Furthermore, identification of bacteria enriched by agavins opens opportunities to explore new probiotics.

Keywords: agavins; body weight loss; microbiota; overweight; prebiotics; short chain fatty acids.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
High-fat diet consumption for five weeks induced overweight and modified the cecal microbiota composition of mice. Body weight gain (A); bacterial alpha diversity in cecum according to diet (B); principal coordinate analysis (PCoA) plot of cecal communities (C); linear discriminant analysis showing the differentially-overrepresented genera between mice fed with standard and high-fat diets (D); and the effect of the diet on the Firmicutes/Bacteroidetes ratio (E). Treatments with different superscript letters indicate significant differences (t test, p < 0.05).
Figure 2
Figure 2
The effect of the diet shift and prebiotic supplementation on body weight loss and cecal microbiota composition in overweight mice. Body weight loss (A); Firmicutes/Bacteroidetes (F/B) ratio after the switch to a standard diet alone, or supplemented with agavins or oligofructose (B); differences in relative abundance of bacterial taxa in cecum according to diet group (C). Each taxon representing >1% of the average relative abundance in study groups is indicated by a different color.
Figure 3
Figure 3
The effect of the diet shift and prebiotic supplementation on the cecal microbiota composition of overweight mice. Bacterial alpha diversity in cecum according to diet group (A); treatments with different superscript letters indicate significant differences (Bonferroni’s test, p < 0.05). Principal coordinate analysis (PCoA) plot of cecal communities (B). Weighted UniFrac distances were used to evaluate beta diversity.
Figure 4
Figure 4
Linear discriminant analysis showing the differentially-overrepresented genera between overweight mice fed with: a high-fat diet and the diet shift (A); the diet shift and agavins supplement (B); the diet shift and oligofructose supplement (C); and agavins and oligofructose supplements (D). LDA effect size (3.0-fold) was used to determine the significant biomarkers.

References

    1. López M.G., Mancilla-Margalli N.A., Mendoza-Diaz G. Molecular structures of fructans from Agave tequilana Weber var. azul. J. Agric. Food Chem. 2003;51:7835–7840. doi: 10.1021/jf030383v.
    1. Mancilla-Margalli N.A., López M.G. Water-soluble carbohydrates and fructan structure patterns from Agave and Dasylirion species. J. Agric. Food Chem. 2006;54:7832–7839. doi: 10.1021/jf060354v.
    1. Mellado-Mojica E., López M.G. Fructan metabolism in A. tequilana Weber blue variety along its developmental cycle in the field. J. Agric. Food Chem. 2012;60:11704–11713. doi: 10.1021/jf303332n.
    1. Gibson G.R., Scott K.P., Rastall R.A., Tuohy K.M., Hotchkiss A., Dubert-Ferrandon A., Gareau M., Murphy E.F., Saulnier D., Loh G., et al. Dietary prebiotics: Current status and new definition. Food Sci. Technol. Bull. Funct. Foods. 2010;7:1–19. doi: 10.1616/1476-2137.15880.
    1. Psichas A., Sleeth M.L., Murphy K.G., Brooks L., Bewick G.A., Hanyaloglu A.C., Ghatei M.A., Bloom S.R., Frost G. The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents. Int. J. Obes. 2015;39:424–429. doi: 10.1038/ijo.2014.153.
    1. Tolhurst G., Heffron H., Lam Y.S., Parker H.E., Habib A.M., Diakogiannaki E., Cameron J., Grosse J., Reimann F., Gribble F.M. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-couples receptor FFAR2. Diabetes. 2012;61:364–371. doi: 10.2337/db11-1019.
    1. Lin H.V., Frassetto A., Kowalik E.J., Jr., Nawrocki A.R., Lu M.M., Kosinski J.R., Hubert J.A., Szeto D., Yao X., Forrest G., et al. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acids receptor 3-independent mechanisms. PLoS ONE. 2012;7:e35240. doi: 10.1371/journal.pone.0035240.
    1. Duncan S.H., Louis P., Thomson J.M., Flint H.J. The role of pH in determining the species composition on the human colonic microbiota. Environ. Microbiol. 2009;11:2112–2122. doi: 10.1111/j.1462-2920.2009.01931.x.
    1. Chung W.S., Walker A.W., Louis P., Parkhill J., Vermeiren J., Bosscher D., Duncan S.H., Flint H.J. Modulation of the human gut microbiota by dietary fibres occurs at the species level. BMC Biol. 2016;14:3. doi: 10.1186/s12915-015-0224-3.
    1. Santiago-García P.A., López M.G. Agavins from Agave angustifolia and Agave potatorum affect food intake, body weight gain and satiety-related hormones (GLP-1 and ghrelin) in mice. Food Funct. 2014;5:3311–3319. doi: 10.1039/C4FO00561A.
    1. Márquez-Aguirre A.L., Camacho-Ruíz R.M., Gutiérrez-Mercado Y.K., Padilla-Camberos E., González-Ávila M., Gálvez-Gastélum F.J., Díaz-Martínez N.E., Ortuño-Sahagún D. Fructans from Agave tequilana with a lower degree of polymerization prevent weight gain, hyperglycemia and liver steatosis in high-fat diet-induced obese mice. Plant Foods Hum. Nutr. 2016;71:416–421. doi: 10.1007/s11130-016-0578-x.
    1. Márquez-Aguirre A.L., Camacho-Ruiz R.M., Arriaga-Alba M., Padilla-Camberos E., Kirchmayr M.R., Blasco J.L., González-Avila M. Effects of Agave tequilana fructans with different degree of polymerization profiles on the body weight, blood lipids and count of fecal Lactobacilli/Bifidobacteria in obese mice. Food Funct. 2013;4:1237–1244. doi: 10.1039/c3fo60083a.
    1. Rendón-Huerta J.A., Juárez-Flores B., Pinos-Rodríguez J.M., Aguirre-Rivera J., Delgado-Portales R.E. Effects of different sources of fructans on body weight, blood metabolites and fecal bacteria in normal and obese non-diabetic and diabetic rats. Plant Foods Hum. Nutr. 2012;67:64–70. doi: 10.1007/s11130-011-0266-9.
    1. Mao B., Li D., Zhao J., Liu X., Gu Z., Chen Y.Q., Zhang H., Chen W. Metagenomic insight into the effects of fructo-oligosaccharides (FOS) on the composition of fecal microbiota in mice. J. Agric. Food Chem. 2015;63:856–863. doi: 10.1021/jf505156h.
    1. Everard A., Lazarevic V., Gaïa N., Johansson M., Ståhlman M., Backhed F., Delzenne N.M., Schrenzel J., François P., Cani P.D. Microbiome of prebiotic-treated mice reveals novel targets involved in host response during obesity. ISME J. 2014;8:2116–2130. doi: 10.1038/ismej.2014.45.
    1. Schneeberger M., Everard A., Gómez-Valadés A.G., Matamoros S., Ramírez S., Delzenne N.M., Gomis R., Claret M., Cani P.D. Akkermansia muciniphila inversely correlates with the onset of inflammation, altered adipose tissue metabolism and metabolic disorders during obesity in mice. Sci. Rep. 2015;5:16643. doi: 10.1038/srep16643.
    1. Ravussin Y., Koren O., Spor A., LeDuc C., Gutman R., Stombaugh J., Knight R., Ley R.E., Libel R.L. Responses of gut microbiota to diet composition and weight loss in lean and obese mice. Obesity. 2012;20:738–747. doi: 10.1038/oby.2011.111.
    1. Zhang C., Zhang M., Pang X., Zhao Y., Wang L., Zhao L. Structural resilience of the gut microbiota in adult mice under high-fat dietary perturbations. ISME J. 2012;6:1848–1857. doi: 10.1038/ismej.2012.27.
    1. Murphy E.F., Cotter P.D., Healy S., Marques T.M., O’Sullivan O., Fouhy F., Clarke S.F., O’Toole P.W., Quigley E.M., Stanton C., et al. Composition and energy harvesting capacity of the gut microbiota: Relationship to diet, obesity and time in mouse models. Gut. 2010;59:1635–1642. doi: 10.1136/gut.2010.215665.
    1. Ley R.E., Bäckhed F., Turnbaugh P., Lozupone C.A., Knight R.D., Gordon J.I. Obesity alters gut microbial ecology. Proc. Natl. Acad. Sci. USA. 2005;102:11070–11075. doi: 10.1073/pnas.0504978102.
    1. Huazano-García A., López M.G. Agavins reverse the metabolic disorders in overweight mice through the increment of short chain fatty acids and hormones. Food Funct. 2015;6:3720–3727. doi: 10.1039/C5FO00830A.
    1. Everard A., Belzer C., Geurts L., Ouwerkerk J.P., Druart C., Bindels L.B., Guiot Y., Derrien M., Muccioli G.G., Delzenne N.M., et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc. Natl. Acad. Sci. USA. 2013;110:9066–9071. doi: 10.1073/pnas.1219451110.
    1. Caporaso J.G., Lauber C.L., Walters W.A., Berg-Lyons D., Huntley J., Fierer N., Owens S.M., Betley J., Fraser L., Bauer M., et al. Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms. ISME J. 2012;6:1621–1624. doi: 10.1038/ismej.2012.8.
    1. Caporaso J.G., Kuczynski J., Stombaugh J., Bittinger K., Bushman F.D., Costello E.K., Fierer N., Peña A.G., Goodrich J.K., Gordon J.I., et al. QIIME allows analysis of high-throughput community sequencing data. Nat. Methods. 2010;7:335–336. doi: 10.1038/nmeth.f.303.
    1. Segata N., Izard J., Waldron L., Gevers D., Miropolsky L., Garrett W.S., Huttenhower C. Metagenomic biomarker discovery and explanation. Genome Biol. 2011;12:R60. doi: 10.1186/gb-2011-12-6-r60.
    1. Femia A.P., Luceri C., Dolara P., Giannini A., Biggeri A., Salvadori M., Clune Y., Collins K.J., Paglierani M., Caderni G. Antitumorigenic activity of the prebiotic inulin enriched with oligofructose in combination with the probiotics Lactobacillus rhamnosus and Bifidobacterium lactis on azoxymethane-induced colon carcinogenesis in rats. Carcinogenesis. 2002;23:1953–1960. doi: 10.1093/carcin/23.11.1953.
    1. Long R.T., Zeng W.S., Chen L.Y. Bifidobacterium as an oral delivery carrier of oxyntomodulin for obesity therapy: Inhibitory effects on food intake and body weight in overweight mice. Int. J. Obes. 2010;34:712–719. doi: 10.1038/ijo.2009.277.
    1. Hannelore D., Moghaddas Gholami A., Berry D., Desmarchelier C., Hahne H., Loh G., Mondot S., Lepage P., Rothballer M., Walker A., et al. High-fat diet alters gut microbiota physiology in mice. ISME J. 2014;8:295–308.
    1. Hildebrandt M.A., Hoffmann C., Sherrill-Mix S.A., Keilbaugh S.A., Hamady M., Chen Y.Y., Knight R., Ahima R.S., Bushman F., Wu G.D. High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology. 2009;137:1716–1724. doi: 10.1053/j.gastro.2009.08.042.
    1. Turnbaugh P.J., Bäckhed F., Fulton L., Gordon J.I. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe. 2008;3:213–223. doi: 10.1016/j.chom.2008.02.015.
    1. Devkota S., Wang Y., Musch M.W., Leone V., Fehlner-Peach H., Nadimpalli A., Antonopoulos D.A., Jabri B., Chang E.B. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10−/− mice. Nature. 2012;487:104–108. doi: 10.1038/nature11225.
    1. Lawrence A.D., Maurice C.F., Carmody R.N., Gootenberg D.B., Button J.E., Wolfe B.E., Ling A.V., Devlin A.S., Varma Y., Fischbach M.A., et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505:559–563.
    1. Flint H.J., Duncan S.H., Scott K.P., Louis P. Links between diet, gut microbiota composition and gut metabolism. Proc. Nutr. Soc. 2015;74:13–22. doi: 10.1017/S0029665114001463.
    1. Bindels L.B., Neyrinck A.M., Salazar N., Taminiau B., Druart C., Muccioli G.G., François E., Blecker C., Richel A., Daube G., et al. Non digestible oligosaccharides modulate the gut microbiota to control the development of leukemia and associated cachexia in mice. PLoS ONE. 2015;10:e0131009. doi: 10.1371/journal.pone.0131009.
    1. Frost G., Sleeth M.L., Sahuri-Arisoylu M., Lizarbe B., Cerdan S., Brody L., Anastasovska J., Ghourab S., Hankir M., Zhang S., et al. The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nat. Commun. 2014;5:3611. doi: 10.1038/ncomms4611.
    1. Chang C.J., Lin C.S., Lu C.C., Martel J., Ko Y.F., Ojcius D.M., Tseng S.F., Wu T.R., Chen Y.Y., Young J.D., et al. Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota. Nat. Commun. 2015;6:7489. doi: 10.1038/ncomms8489.
    1. Liou A.P., Paziuk M., Luevano J.M., Jr., Machineni S., Turnbaugh P.J., Kaplan L.M. Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity. Sci. Transl. Med. 2013;5:178ra41. doi: 10.1126/scitranslmed.3005687.
    1. Tremaroli V., Karlsson F., Werling M., Ståhlman M., Kovatcheva-Datchary P., Olbers T., Fändriks L., le Roux C.W., Nielsen J., Bäckhed F. Roux-en-Y gastric bypass and vertical banded gastroplasty induce long-term changes on the human gut microbiome contribution to fat mass regulation. Cell Metal. 2015;22:228–238. doi: 10.1016/j.cmet.2015.07.009.
    1. Zhang H., DiBaise J.K., Zuccolo A., Kudrna D., Braidotti M., Yu Y., Parameswaran P., Crowell M.D., Wing R., Rittmann B.E., et al. Human gut microbiota in obesity and after gastric bypass. Proc. Natl. Acad. Sci. USA. 2009;106:2365–2370. doi: 10.1073/pnas.0812600106.
    1. Mahowald M.A., Rey F.E., Seedorf H., Turnbaugh P.J., Fulton R.S., Wollan A., Shah N., Wang C., Magrini V., Wilson R.K., et al. Characterizing a model human gut microbiota composed of members of its two dominant bacterial phyla. Proc. Natl. Acad. Sci. USA. 2009;106:5859–5864. doi: 10.1073/pnas.0901529106.

Source: PubMed

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