Abstract
Bacteria capable of producing electricity in intestinal microbiota have been discovered. However, no studies have explored butyric acid which generated by electrogenic bacteria on the host organism have significant physiological impacts on certain organs. We found that the capacity for electrical current generation by the commensal gut Leuconostoc mesenteroides EH-1 (L. mesenteroides EH-1) during glucose fermentation. The electricity production was essential for the gut colonization of L. mesenteroides EH-1 since the inhibition of electricity production by cyclophilin A inhibitor (TMN355) significantly diminished the number of bacteria attached to the human gut epithelial cell surface. The adipocyte differentiation contributes to the increased 4-hydroxy-2-nonenal (4-HNE), considered as a biomarker of reactive oxygen species (ROS). The effect of intestinal electrogenic microbiota in the high-fat diet (HFD)-induced 4-HNE and abdominal fat accumulation in mice was investigated in this study. The oral administration of glucose with a butyric acid-producing L. mesenteroides EH-1 bacterium attenuated the expression of 4-HNE and abdominal fat. The level of 4-HNE and abdominal fat depot were markedly increased in mice administered with cyclophilin A inhibitor-pretreated bacteria or GLPG-0974, an antagonist of free fatty acid receptor 2 (Ffar2). Our studies suggest a novel means by which the probiotic bacteria can modulate fat mass deposition and oxidative stress via the cyclophilin A-mediated electron production and the butyric acid-activated Ffar2 pathway.
Similar content being viewed by others
Data availability
All data generated or analyzed during this study are included in this published article [and its supplementary information files].
References
Abubakr MA, Hassan Z, Salem G (2013) Antioxidant activity of milk fermented with Lactobacillus plantarum and Leuconostoc mesenteroides isolated from non-dairy sources. Asian J Pharm Res Dev 1:71–83
Adachi T, Toishi T, Wu H, Kamiya T, Hara H (2009) Expression of extracellular superoxide dismutase during adipose differentiation in 3T3-L1 cells. Redox Rep 14:34–40
Akbar S, Bellary S, Griffiths HR (2011) Dietary antioxidant interventions in type 2 diabetes patients: a meta-analysis. Br J Diabetes Vasc Dis 11:62–68
Almeida-Suhett CP, Scott JM, Graham A, Chen Y, Deuster PA (2019) Control diet in a high-fat diet study in mice: Regular chow and purified low-fat diet have similar effects on phenotypic, metabolic, and behavioral outcomes. Nutr Neurosci 22:19–28
Balcázar JL et al (2007) Changes in intestinal microbiota and humoral immune response following probiotic administration in brown trout (Salmo trutta). Br J Nutr 97:522–527
Barella LF, Jain S, Kimura T, Pydi SP (2021) Metabolic roles of G protein-coupled receptor signaling in obesity and type 2 diabetes. FEBS J 288:2622–2644
Barzegar A (2012) The role of electron-transfer and H-atom donation on the superb antioxidant activity and free radical reaction of curcumin. Food Chem 135:1369–1376
Bjelakovic G, Nikolova D, Gluud C (2013) Antioxidant supplements to prevent mortality. JAMA 310:1178–1179
Brown AJ et al (2003) The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem 278:11312–11319
Cani PD, Delzenne NM (2009) Interplay between obesity and associated metabolic disorders: new insights into the gut microbiota. Curr Opin Pharm 9:737–743
Cani PD et al (2007) Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56:1761–1772
Castro JP, Grune T, Speckmann B (2016) The two faces of reactive oxygen species (ROS) in adipocyte function and dysfunction. Biol Chem 397:709–724
Chattopadhyay M, Khemka VK, Chatterjee G, Ganguly A, Mukhopadhyay S, Chakrabarti S (2015) Enhanced ROS production and oxidative damage in subcutaneous white adipose tissue mitochondria in obese and type 2 diabetes subjects. Mol Cell Biochem 399:95–103
Chen C, Shen Y, An D, Voordouw G (2017) Use of acetate, propionate, and butyrate for reduction of nitrate and sulfate and methanogenesis in microcosms and bioreactors simulating an oil reservoir. Appl Environ Microbiol 83:e02983–e02916
Chen C-Y, Tsai T-H, Wu P-S, Tsao S-E, Huang Y-S, Chung Y-C (2018) Selection of electrogenic bacteria for microbial fuel cell in removing Victoria blue R from wastewater. J Environ Sci Health 53:108–115
Coppola S, Avagliano C, Calignano A, Berni Canani R (2021) The protective role of butyrate against obesity and obesity-related diseases. Molecules 26:682
Czernichow S et al (2009) Effects of long-term antioxidant supplementation and association of serum antioxidant concentrations with risk of metabolic syndrome in adults. Am J Clin Nutr 90:329–335
d’Uscio LV, Milstien S, Richardson D, Smith L, Katusic ZS (2003) Long-term vitamin C treatment increases vascular tetrahydrobiopterin levels and nitric oxide synthase activity. Circul Res 92:88–95
Darzi J, Frost GS, Robertson MD (2011) Do SCFA have a role in appetite regulation? Proc Nutr Soc 70:119–128
Dewulf EM et al (2011) Inulin-type fructans with prebiotic properties counteract GPR43 overexpression and PPARγ-related adipogenesis in the white adipose tissue of high-fat diet-fed mice. J Nutr Biochem 22:712–722
Di Domenico EG, Petroni G, Mancini D, Geri A, Palma LD, Ascenzioni F (2015) Development of electroactive and anaerobic ammonium-oxidizing (Anammox) biofilms from digestate in microbial fuel cells. BioMed Res Intern 2015
Duncan SH, Belenguer A, Holtrop G, Johnstone AM, Flint HJ, Lobley GE (2007) Reduced dietary intake of carbohydrates by obese subjects results in decreased concentrations of butyrate and butyrate-producing bacteria in feces. Appl Environ Microbiol 73:1073–1078
Ericsson AC, Davis DJ, Franklin CL, Hagan CE (2015) Exoelectrogenic capacity of host microbiota predicts lymphocyte recruitment to the gut. Physiol Genomics 47:243–252
Finke N, Vandieken V, Jørgensen BB (2007) Acetate, lactate, propionate, and isobutyrate as electron donors for iron and sulfate reduction in Arctic marine sediments, Svalbard. FEMS Microbiol Ecol 59:10–22
Fleury Y et al (1996) Covalent structure, synthesis, and structure-function studies of mesentericin Y 10537, a defensive peptide from Gram-positive bacteria Leuconostoc mesenteroides. J Biol Chem 271:14421–14429
Furukawa S et al (2017) Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 114:1752–1761
Hajer GR, van Haeften TW, Visseren FLJ (2008) Adipose tissue dysfunction in obesity, diabetes, and vascular diseases. Eur Heart J 29:2959–2971. https://doi.org/10.1093/eurheartj/ehn387
Hall JE, Hall ME (2020) Guyton and Hall textbook of medical physiology e-Book. Elsevier, Philadelphia
He J et al (2020) Short-chain fatty acids and their association with signalling pathways in inflammation, glucose and lipid metabolism. Int J Mol Sci 21:6356
Houstis N, Rosen ED, Lander ES (2006) Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature 440:944–948
Huang A, Vita JA, Venema RC, Keaney JF (2000) Ascorbic acid enhances endothelial nitric-oxide synthase activity by increasing intracellular tetrahydrobiopterin. J Biol Chem 275:17399–17406
Jakobsdottir G, Xu J, Molin G, Ahrne S, Nyman M (2013) High-fat diet reduces the formation of butyrate, but increases succinate, inflammation, liver fat and cholesterol in rats, while dietary fibre counteracts these effects. PLoS ONE 8:e80476
Jeffery IB, Lynch DB, O’toole PW (2016) Composition and temporal stability of the gut microbiota in older persons. ISME J 10:170–182
Jiao W et al (2020) Butyric acid normalizes hyperglycemia caused by the tacrolimus-induced gut microbiota. Am J Transplantation 20:2413–2424
Jocken JW et al (2018) Short-chain fatty acids differentially affect intracellular lipolysis in a human white adipocyte model. Front Endocrinol (lausanne) 8:372
Jung JY, Lee SH, Lee HJ, Seo H-Y, Park W-S, Jeon CO (2012) Effects of Leuconostoc mesenteroides starter cultures on microbial communities and metabolites during kimchi fermentation. Int J Food Microbiol 153:378–387
Kashmiri Z, Mankar S (2014) Free radicals and oxidative stress in bacteria. Int J Curr Microbiol App Sci 3:34–40
Khan S, Jena G (2014) Protective role of sodium butyrate, a HDAC inhibitor on beta-cell proliferation, function and glucose homeostasis through modulation of p38/ERK MAPK and apoptotic pathways: study in juvenile diabetic rat. Chem-Biol Interact 213:1–12
Kim G et al (2022) Prebiotic activities of dextran from Leuconostoc mesenteroides SPCL742 analyzed in the aspect of the human gut microbial ecosystem. Food Funct 13:1256–1267
Kimura I et al (2013) The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43. Nat Commun 4:1–12
Kuda T et al (2014) In vitro evaluation of the fermentative, antioxidant, and anti-inflammation properties of Lactococcus lactis subsp. lactis BF3 and Leuconostoc mesenteroides subsp. mesenteroides BF7 isolated from Oncorhynchus keta intestines in Rausu. Japan J Funct Foods 11:269–277
Kumar AP, Chougala M, Nandini C, Salimath P (2010) Effect of butyric acid supplementation on serum and renal antioxidant enzyme activities in streptozotocin-induced diabetic rats. J Food Biochem 34:15–30
Lee SP et al (2001) Cyclophilin a binds to peroxiredoxins and activates its peroxidase activity. J Biol Chem 276:29826–29832
Lee J, Ozcelik B, Min D (2003) Electron donation mechanisms of β-carotene as a free radical scavenger. J Food Sci 68:861–865
Lee OH, Seo MJ, Choi HS, Lee BY (2012) Pycnogenol inhibits lipid accumulation in 3T3-L1 adipocytes with the modulation of reactive oxygen species (ROS) production associated with antioxidant enzyme responses. Phytother Res 26:403–411
Lee Y-J et al (2014) Anti-adipogenic and anti-oxidant activities of mugwort and pine needles fermented using Leuconostoc mesenteroides 1076. Food Biotechnol 28:79–95
Lin HV et al (2012) Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS ONE 7:e35240
Liu S et al (2015) Starch and starch hydrolysates are favorable carbon sources for Bifidobacteria in the human gut. BMC Microbiol 15:1–9
Long EK, Olson DM, Bernlohr DA (2013) High-fat diet induces changes in adipose tissue trans-4-oxo-2-nonenal and trans-4-hydroxy-2-nonenal levels in a depot-specific manner. Free Radical Biol Med 63:390–398
Lu Y, Fan C, Li P, Lu Y, Chang X, Qi K (2016) Short chain fatty acids prevent high-fat-diet-induced obesity in mice by regulating G protein-coupled receptors and gut microbiota. Sci Rep 6:1–13
Marazza JA, Nazareno MA, de Giori GS, Garro MS (2012) Enhancement of the antioxidant capacity of soymilk by fermentation with Lactobacillus rhamnosus. J Funct Foods 4:594–601
Matheus V, Monteiro L, Oliveira R, Maschio D, Collares-Buzato C (2017) Butyrate reduces high-fat diet-induced metabolic alterations, hepatic steatosis and pancreatic beta cell and intestinal barrier dysfunctions in prediabetic mice. Exp Biol Med 242:1214–1226
McNabney SM, Henagan TM (2017) Short chain fatty acids in the colon and peripheral tissues: a focus on butyrate, colon cancer, obesity and insulin resistance. Nutrients 9:1348
Mekkes M, Weenen T, Brummer RJ, Claassen E (2014) The development of probiotic treatment in obesity: a review. Beneficial Microbes 5:19–28
Nelson D, Cox M, Lehninger A (2008) Principles of biochemistry, 5th edn. Freeman New York, New York
Oschman JL (2007) Can electrons act as antioxidants? A review and commentary. J Alternat Complement Med 13:955–967
Pace BS, White GL, Dover GJ, Boosalis MS, Faller DV, Perrine SP (2002) Short-chain fatty acid derivatives induce fetal globin expression and erythropoiesis in vivo. Blood J Am Soc Hematol 100:4640–4648
Pham MT et al (2020) Leuconostoc mesenteroides mediates an electrogenic pathway to attenuate the accumulation of abdominal fat mass induced by high fat diet. Sci Rep 10:21916. https://doi.org/10.1038/s41598-020-78835-9
Reiter RJ (1996) The indoleamine melatonin as a free radical scavenger, electron donor, and antioxidant. In: Filippini GA, Costa CVL, Bertazzo A (eds) Recent Advances in Tryptophan Research. Springer, Boston, MA, pp 307–313
Rosenspire AJ, Kindzelskii AL, Simon BJ, Petty HR (2005) Real-time control of neutrophil metabolism by very weak ultra-low frequency pulsed magnetic fields. Biophys J 88:3334–3347
Shi L et al (2016) Extracellular electron transfer mechanisms between microorganisms and minerals. Nat Rev Microbiol 14:651
Shiro K, Tadao O (2017) Genome sequence of Leuconostoc mesenteroides LK-151 isolated from a Japanese sake cellar as a high producer of d-amino acids. Genome Announc 5:e00661–e00617
Sorokin DY, Detkova E, Muyzer G (2010) Propionate and butyrate dependent bacterial sulfate reduction at extremely haloalkaline conditions and description of Desulfobotulus alkaliphilus sp. nov. Extremophiles 14:71–77
Szekér K, Németh E, Kun S, Beczner J, Gálfi P (2007) Adhesion of lactic acid bacteria to Caco-2 cells—Evaluation of different detection methods. Acta Aliment 36:365–371
Traisaeng S et al (2020) Leuconostoc mesenteroides fermentation produces butyric acid and mediates Ffar2 to regulate blood glucose and insulin in type 1 diabetic mice. Sci Rep 10:1–10
Trémillon N et al (2012) PpiA, a surface PPIase of the cyclophilin family in Lactococcus lactis. PLoS ONE 7:e33516
Uchida K (2003) 4-Hydroxy-2-nonenal: a product and mediator of oxidative stress. Prog Lipid Res 42:318–343
Ulven T (2012) Short-chain free fatty acid receptors FFA2/GPR43 and FFA3/GPR41 as new potential therapeutic targets. Front Endocrinol (lausanne) 3:111
Valacchi G, Caccamo D, Pelle E, De Luca C (2013) Innovative Approaches in Environmental Medicine: Redox/Detoxification Biomarkers in Environmental Intolerances. In. Hindawi
Walker E, Wolfe BM (2020) Obesity Prevention. In: Nguyen NT, Brethauer SA, Morton JM, Ponce J, Rosenthal RJ (eds) The ASMBS Textbook of Bariatric Surgery. Springer International Publishing, Cham, pp 595–611
Wang W et al (2019) Bacterial extracellular electron transfer occurs in mammalian gut. Anal Chem 91:12138–12141
Yadav H, Lee J-H, Lloyd J, Walter P, Rane SG (2013) Beneficial metabolic effects of a probiotic via butyrate-induced GLP-1 hormone secretion. J Biol Chem 288:25088–25097
Yang JJ, Pham MT, Rahim AR, Chuang T-H, Hsieh M-F, Huang C-M (2020a) Mouse Abdominal Fat Depots Reduced by Butyric Acid-Producing Leuconostoc mesenteroides. Microorganisms 8:1180
Yang JJ, Rahim AR, Yang AJ, Chuang T-H, Huang C-M (2020b) Production of electricity and reduction of high-fat diet-induced IL-6 by glucose fermentation of Leuconostoc mesenteroides. Biochem Biophys Res Commun 533:651–656
Yao Y, Cai X, Fei W, Ye Y, Zhao M, Zheng C (2022) The role of short-chain fatty acids in immunity, inflammation and metabolism. Crit Rev Food Sci Nutr 62:1–12
Zhang W et al (2011) Sodium butyrate maintains growth performance by regulating the immune response in broiler chickens. Br Poult Sci 52:292–301
Acknowledgements
This work was supported by Ton Duc Thang University
Funding
The authors received no specific grant from any funding agency.
Author information
Authors and Affiliations
Contributions
MTP was in charge of experiments, wrote, edited, and reviewed manuscript; TDT designed and interpreted study; EZ analyzed data. All authors approved the final version of the manuscript. MTP is the guarantor of this work.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no competing interests.
Additional information
Communicated by Erko Stackebrandt.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Pham, M.T., Tran, T.D. & Zayabaatar, E. Leuconostoc mesenteroides utilizes glucose fermentation to produce electricity and ameliorates high-fat diet-induced abdominal fat mass. Arch Microbiol 204, 670 (2022). https://doi.org/10.1007/s00203-022-03281-2
Received:
Revised:
Accepted:
Published:
DOI: https://doi.org/10.1007/s00203-022-03281-2