Commensal Hafnia alvei strain reduces food intake and fat mass in obese mice-a new potential probiotic for appetite and body weight management.
Journal
International journal of obesity (2005)
ISSN: 1476-5497
Titre abrégé: Int J Obes (Lond)
Pays: England
ID NLM: 101256108
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
27
04
2019
accepted:
11
12
2019
revised:
02
12
2019
pubmed:
9
1
2020
medline:
7
9
2021
entrez:
9
1
2020
Statut:
ppublish
Résumé
Based on the recent identification of E.coli heat shock protein ClpB as a mimetic of the anorexigenic α-melanocyte stimulating hormone (α-MSH), the objective of this study was to preclinically validate Hafnia alvei, a ClpB-producing commensal bacterium as a potential probiotic for appetite and body weight management in overweight and obesity. The involvement of enterobacterial ClpB in the putative anti-obesity effects was studied using ClpB-deficient E.coli. A food-grade H. alvei HA4597 strain synthetizing the ClpB protein with an α-MSH-like motif was selected as a candidate probiotic to be tested in ob/ob and high-fat diet (HFD)-fed obese and overweight mice. The relevance of the enterobacterial ClpB gene to human obesity was studied by in silico analysis of fecal metagenomes of 569 healthy individuals from the "MetaHIT" database. Chronic per os administration of native but not ClpB-deficient E.coli strain reduced body weight gain (p < 0.05) and daily meal frequency (p < 0.001) in ob/ob mice. Oral gavage of H.alvei for 18 and 46 days in ob/ob and HFD-fed obese mice, respectively, was well tolerated, reduced body weight gain and fat mass in both obesity models (p < 0.05) and decreased food intake in hyperphagic ob/ob mice (p < 0.001). Elevated fat tissue levels of phosphorylated hormone-sensitive lipase were detected in H.alvei -treated ob/ob mice (p < 0.01). Enterobacterial ClpB gene richness was lower in obese vs. non-obese humans (p < 0.0001) and correlated negatively with BMI in genera of Enterobacter, Klebsiella and Hafnia. H.alvei HA4597 strain reduces food intake, body weight and fat mass gain in hyperphagic and obese mice. These data combined with low enterobacterial ClpB gene abundance in the microbiota of obese humans provide the rationale for using H.alvei as a probiotic for appetite and body weight management in overweight and obesity.
Sections du résumé
BACKGROUND/OBJECTIVES
Based on the recent identification of E.coli heat shock protein ClpB as a mimetic of the anorexigenic α-melanocyte stimulating hormone (α-MSH), the objective of this study was to preclinically validate Hafnia alvei, a ClpB-producing commensal bacterium as a potential probiotic for appetite and body weight management in overweight and obesity.
METHODS
The involvement of enterobacterial ClpB in the putative anti-obesity effects was studied using ClpB-deficient E.coli. A food-grade H. alvei HA4597 strain synthetizing the ClpB protein with an α-MSH-like motif was selected as a candidate probiotic to be tested in ob/ob and high-fat diet (HFD)-fed obese and overweight mice. The relevance of the enterobacterial ClpB gene to human obesity was studied by in silico analysis of fecal metagenomes of 569 healthy individuals from the "MetaHIT" database.
RESULTS
Chronic per os administration of native but not ClpB-deficient E.coli strain reduced body weight gain (p < 0.05) and daily meal frequency (p < 0.001) in ob/ob mice. Oral gavage of H.alvei for 18 and 46 days in ob/ob and HFD-fed obese mice, respectively, was well tolerated, reduced body weight gain and fat mass in both obesity models (p < 0.05) and decreased food intake in hyperphagic ob/ob mice (p < 0.001). Elevated fat tissue levels of phosphorylated hormone-sensitive lipase were detected in H.alvei -treated ob/ob mice (p < 0.01). Enterobacterial ClpB gene richness was lower in obese vs. non-obese humans (p < 0.0001) and correlated negatively with BMI in genera of Enterobacter, Klebsiella and Hafnia.
CONCLUSIONS
H.alvei HA4597 strain reduces food intake, body weight and fat mass gain in hyperphagic and obese mice. These data combined with low enterobacterial ClpB gene abundance in the microbiota of obese humans provide the rationale for using H.alvei as a probiotic for appetite and body weight management in overweight and obesity.
Identifiants
pubmed: 31911661
doi: 10.1038/s41366-019-0515-9
pii: 10.1038/s41366-019-0515-9
pmc: PMC7188665
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1041-1051Références
Rosenbaum M, Knight R, Leibel RL. The gut microbiota in human energy homeostasis and obesity. Trends Endocrinol Metab. 2015;26:493–501.
doi: 10.1016/j.tem.2015.07.002
Sender R, Fuchs S, Milo R. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol. 2016;14:e1002533.
doi: 10.1371/journal.pbio.1002533
Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, et al. Human gut microbiome viewed across age and geography. Nature. 2012;486:222–7.
doi: 10.1038/nature11053
Bolnick DI, Snowberg LK, Hirsch PE, Lauber CL, Org E, Parks B, et al. Individual diet has sex-dependent effects on vertebrate gut microbiota. Nat Commun. 2014;5:4500.
doi: 10.1038/ncomms5500
Cotillard A, Kennedy SP, Kong LC, Prifti E, Pons N, Le Chatelier E, et al. Dietary intervention impact on gut microbial gene richness. Nature. 2013;500:585–8.
doi: 10.1038/nature12480
Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444:1027–131.
doi: 10.1038/nature05414
Fetissov SO. Role of the gut microbiota in host appetite control: bacterial growth to animal feeding behaviour. Nat Rev Endocrinol. 2017;13:11–25.
doi: 10.1038/nrendo.2016.150
Muscogiuri G, Cantone E, Cassarano S, Tuccinardi D, Barrea L, Savastano S, et al. Gut microbiota: a new path to treat obesity. Int J Obes Suppl. 2019. https://doi.org/10.1038/s41367-019-0011-7 .
Kobyliak N, Conte C, Cammarota G, Haley AP, Styriak I, Gaspar L, et al. Probiotics in prevention and treatment of obesity: a critical view. Nutr Metab (Lond). 2016;13:14.
doi: 10.1186/s12986-016-0067-0
Crovesy L, Ostrowski M, Ferreira DMTP, Rosado EL, Soares-Mota M. Effect of Lactobacillus on body weight and body fat in overweight subjects: a systematic review of randomized controlled clinical trials. Int J Obes. 2017;41:1607.
doi: 10.1038/ijo.2017.161
Cani PD, de Vos WM. Next-generation beneficial microbes: the case of akkermansia muciniphila. Front Microbiol. 2017;8:1765.
Tennoune N, Chan P, Breton J, Legrand R, Chabane YN, Akkermann K, et al. Bacterial ClpB heat-shock protein, an antigen-mimetic of the anorexigenic peptide [alpha]-MSH, at the origin of eating disorders. Transl Psychiatry. 2014;4:e458.
doi: 10.1038/tp.2014.98
Yaswen L, Diehl N, Brennan MB, Hochgeschwender U. Obesity in the mouse model of pro-opiomelanocortin deficiency responds to peripheral melanocortin. Nat Med. 1999;5:1066–70.
doi: 10.1038/12506
Krude H, Biebermann H, Luck W, Horn R, Brabant G, Gruters A. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet. 1998;19:155–7.
doi: 10.1038/509
Farooqi IS, Keogh JM, Yeo GSH, Lank EJ, Cheetham T, O'Rahilly S. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med. 2003;348:1085–95.
doi: 10.1056/NEJMoa022050
Adeolu M, Alnajar S, Naushad S, S. Gupta R. Genome-based phylogeny and taxonomy of the ‘Enterobacteriales’: proposal for Enterobacterales ord. nov. divided into the families Enterobacteriaceae, Erwiniaceae fam. nov., Pectobacteriaceae fam. nov., Yersiniaceae fam. nov., Hafniaceae fam. nov., Morganellaceae fam. nov., and Budviciaceae fam. nov. Int J Syst Evol Microbiol. 2016;66:5575–99.
doi: 10.1099/ijsem.0.001485
Li J, Jia H, Cai X, Zhong H, Feng Q, Sunagawa S, et al. An integrated catalog of reference genes in the human gut microbiome. Nat Biotechnol. 2014;32:834.
doi: 10.1038/nbt.2942
Breton J, Tennoune N, Lucas N, François M, Legrand R, Jacquemot J, et al. Gut commensal E.coli proteins activate host satiety pathways following nutrient-induced bacterial growth. Cell Metab. 2016;23:1–11.
doi: 10.1016/j.cmet.2015.10.017
Turner S, Pryer KM, Miao VPW, Palmer JD. Investigating deep phylogenetic relationships among cyanobacteria and plastids by small subunit rRNA sequence analysis1. J Eukaryotic Microbiol. 1999;46:327–38.
doi: 10.1111/j.1550-7408.1999.tb04612.x
Hamze Sinno M, Do Rego JC, Coëffier M, Bole-Feysot C, Ducrotte P, Gilbert D, et al. Regulation of feeding and anxiety by α-MSH reactive autoantibodies. Psychoneuroendocrinology. 2009;34:140–9.
doi: 10.1016/j.psyneuen.2008.08.021
Moller V. Distribution of amino acid decarboxylases in Enterobacteriaceae. Acta Pathol Microbiol Scand. 1954;35:259–77.
doi: 10.1111/j.1699-0463.1954.tb00869.x
Gaya P, Medina M, Nuntez M. Enterobacteriaceae, coliforms, faecal coliforms and salmonellas in raw ewes'milk. J Appl Bacteriol. 1987;62:321–6.
doi: 10.1111/j.1365-2672.1987.tb04927.x
Tornadijo E, Fresno JM, Carballo J, Martín-Sarmiento R. Study of Enterobacteriaceae throughout the manufacturing and ripening of hard goats' cheese. J Appl Bacteriol. 1993;75:240–6.
doi: 10.1111/j.1365-2672.1993.tb02772.x
Richard J, Zadi H. Inventaire de la flore bactérienne dominante des Camemberts fabriqués avec lait cru. Le Lait, INRA Ed. 1983;63:25–42.
doi: 10.1051/lait:1983623-6243
Federation ID. Safety demonstration of microbial food cultures (MFC) in fermented food products (Annex 4). Bull Int Dairy Fed. 2012;455:68.
Mogren L, Windstam S, Boqvist S, Vågsholm I, Söderqvist K, Rosberg AK, et al. The hurdle approach—a holistic concept for controlling food safety risks associated with pathogenic bacterial contamination of leafy green vegetables. A Review. Front Microbiol. 2018;9:1965.
Richard D. Cognitive and autonomic determinants of energy homeostasis in obesity. Nat Rev Endocrinol. 2015;11:489.
doi: 10.1038/nrendo.2015.103
Anderson EJP, Çakir I, Carrington SJ, Cone RD, Ghamari-Langroudi M, Gillyard T, et al. 60 YEARS OF POMC: regulation of feeding and energy homeostasis by α-MSH. J Mol Endocrinol. 2016;56:T157–T74.
doi: 10.1530/JME-16-0014
Kühnen P, Clément K, Wiegand S, Blankenstein O, Gottesdiener K, Martini LL, et al. Proopiomelanocortin deficiency treated with a melanocortin-4 receptor agonist. N Engl J Med. 2016;375:240–6.
doi: 10.1056/NEJMoa1512693
Qiang X, Liotta AS, Shiloach J, Gutierrez JC, Wang H, Ochani M, et al. New melanocortin-like peptide of E. coli can suppress inflammation via the mammalian melanocortin-1 receptor (MC1R): possible endocrine-like function for microbes of the gut. NPJ Biofilms Microb. 2017;3:31.
doi: 10.1038/s41522-017-0039-9
Fetissov SO, Legrand R, Lucas N. Bacterial protein mimetic of peptide hormone as a new class of protein-based drugs. Curr Med Chem. 2019;26:546–53.
doi: 10.2174/0929867324666171005110620
Dominique M, Breton J, Guérin C, Bole-Feysot C, Lambert G, Déchelotte P, et al. Effects of macronutrients on the in vitro production of ClpB, a bacterial mimetic protein of α-MSH and its possible role in the satiety signaling. Nutrients. 2019;11:2115.
doi: 10.3390/nu11092115
Cox HM, Tough IR, Woolston A-M, Zhang L, Nguyen AD, Sainsbury A, et al. Peptide YY is critical for acylethanolamine receptor Gpr119-induced activation of gastrointestinal mucosal responses. Cell Metab. 2010;11:532–42.
doi: 10.1016/j.cmet.2010.04.014
Ericson MD, Schnell SM, Freeman KT, Haskell-Luevano C. A fragment of the Escherichia coli ClpB heat-shock protein is a micromolar melanocortin 1 receptor agonist. Bioorg Med Chem Lett. 2015;25:5306–8.
doi: 10.1016/j.bmcl.2015.09.046
Batterham RL, Cowley MA, Small CJ, Herzog H, Cohen MA, Dakin CL, et al. Gut hormone PYY(3-36) physiologically inhibits food intake. Nature. 2002;418:650–4.
doi: 10.1038/nature00887
Panaro Brandon L, Tough Iain R, Engelstoft Maja S, Matthews Robert T, Digby Gregory J, Møller Cathrine L, et al. The melanocortin-4 receptor is expressed in enteroendocrine L cells and regulates the release of peptide YY and glucagon-like peptide 1 in vivo. Cell Metab. 2014;20:1018–29.
doi: 10.1016/j.cmet.2014.10.004
Million M, Angelakis E, Maraninchi M, Henry M, Giorgi R, Valero R, et al. Correlation between body mass index and gut concentrations of Lactobacillus reuteri, Bifidobacterium animalis, Methanobrevibacter smithii and Escherichia coli. Int J Obes. 2013;37:1460–6.
doi: 10.1038/ijo.2013.20