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European Journal of Nutrition

, Volume 57, Issue 8, pp 2897–2911 | Cite as

Co-supplementation of isomalto-oligosaccharides potentiates metabolic health benefits of polyphenol-rich cranberry extract in high fat diet-fed mice via enhanced gut butyrate production

  • Dhirendra Pratap Singh
  • Shashank Singh
  • Vandana Bijalwan
  • Vijay Kumar
  • Pragyanshu Khare
  • Ritesh Kumar Baboota
  • Paramdeep Singh
  • Ravneet Kaur Boparai
  • Jagdeep Singh
  • Kanthi Kiran KondepudiEmail author
  • Kanwaljit ChopraEmail author
  • Mahendra BishnoiEmail author
Original Contribution

Abstract

Purpose

Cranberries are a rich source of polyphenolic antioxidants. Purified sugars or artificial sweeteners are being added to cranberry-based food products to mask tartness. Refined sugar and artificial sweeteners intake modulate gut microbiota and result in metabolic complications. We evaluated effects of isomalto-oligosaccharides (IMOs; sweet tasting non-digestible oligosaccharides) with cranberry extract (CRX) on high fat diet (HFD)-induced metabolic alterations in mice.

Methods

Male Swiss albino mice were fed normal chow or HFD (58% fat kcal), and were administered either CRX (200 mg/kg) alone or in combination with IMOs (1 g/kg). Cecal short-chain fatty acids, abundances of selected (1) butyrate producing, (2) metabolically beneficial, and (3) selective lipopolysaccharides producing gram negative gut bacteria were studied. Further, gut-related histological, biochemical, genomic changes along with circulating pro-/anti-inflammatory markers and systemic obesity-associated metabolic changes were studied.

Results

Co-supplementation of CRX and IMOs significantly improved cecal SCFAs, especially butyrate levels, selected butyrate-producing bacteria (clostridial cluster XIVa bacteria) and butyrate kinase expression in HFD-fed mice. The combination also significantly improved gut beneficial bacterial abundance, gut histology and related changes (colon mucin production, gut permeability) as compared to individual agents. It also prevented HFD-induced systemic and tissue inflammation, glucose intolerance and systemic obesity-associated metabolic changes in adipose tissue and liver. The combination of CRX and IMOs appeared more effective in the prevention of HFD-induced gut derangements.

Conclusion

Combination of CRX and IMOs could be advantageous for normalization of metabolic alterations seen in diet-induced obesity via beneficial modulation of gastrointestinal health.

Keywords

Butyrate Cranberry extract Ectopic fat Isomalto-oligosaccharides Polyphenols Mucin 

Abbreviations

ACC

Acetyl-CoA carboxylase

ACOX-1

Acyl-coenzyme A oxidase 1

AKK

Akkermansia muciniphila

ANERO

Anaerostipes butyraticus

BACT

Bacteroidetes

BFRAG

Bacteroides sp.

BIF

Bifidobacteria

BPULL

Butyricicoccus pullicaecorum

BVIB

Butyrivibrio sp.

C/EBPα

CCAAT/enhancer-binding protein alpha

CITRO

Citrobacter sp.

Cld

Claudin

CLEP

Clostridium sp.

CPROP

Clostridium propionicum

CRX

Cranberry extract

ECOL

Escherichia coli

ENT

Enterobacter sp.

ENTB

Enterobacteriaceae

EUBACT

Eubacterium sp.

FASN

Fatty acid synthase

FEC

Faecalibacterium sp.

FFAR

Free fatty acid receptors

FIRM

Firmicutes

G6Pase

Glucose-6-phosphatase

gCCoC

Clostridium coccoides group

GK

Glucokinase

GYS-2

Glycogen synthase-2

HFD

High-fat diet

HOMA

Homeostasis model assessment

HSL

Hormone sensitive lipase

IMOs

Isomalto-oligosaccharides

KLEB

Klebsiella sp.

LAB

Lactobacillus sp.

LACH

Lachnospiraceae

LPS

Lipopolysaccharides

MCP-1

Macrophagic chemoattractant protein-1

MUC

Mucin

MyD88

Myeloid differentiation primary response gene 88

NEFA

Nonesterified fatty acids

NFκB

Nuclear factor kappa beta

NPD

Normal pellet diet/ normal chow

PEPCK

Phosphoenolpyruvate carboxykinase

PPAR

Peroxisome proliferator-activated receptor

PREVO

Prevotella sp.

RH

Relative humidity

ROS

Roseburia sp.

SCFAs

Short chain fatty acids

SFB

Segmented filamentous bacteria

SOCS3

Suppressor of cytokine signalling 3

TLR

Toll like receptors

TNF-α

Tumor necrosis factor-α

vWAT

Visceral white adipose tissue

ZO

Zona occludens

Notes

Acknowledgements

Authors would like to thank Executive Director, National Agri-food Biotechnology Institute (NABI) for providing infrastructural facility to carry out this work and making intramural grants available to Dr. Mahendra Bishnoi and Dr. Kanthi Kiran Kondepudi. Authors would like to thank DBT-eLibrary Consortium (DelCON) for providing online literature resources.

Authors’ contribution

MB, KC, KKK and DPS conceived the study; DPS, SS, VB, VK, PK, RKB(1,4), and PS did experiments; DPS and MB analyzed all the data; DPS, MB, KKK, RKB(5) and KC wrote the manuscript. All authors critically reviewed the manuscript and approved for final submission.

Compliance with ethical standards

Conflict of interest

There are no conflicts of interest among any of the contributing author of this manuscript.

Supplementary material

394_2017_1561_MOESM1_ESM.docx (15 kb)
Supplementary material 1 (DOCX 15 KB)
394_2017_1561_MOESM2_ESM.docx (24 kb)
Supplementary material 2 (DOCX 23 KB)
394_2017_1561_MOESM3_ESM.docx (22 kb)
Supplementary material 3 (DOCX 22 KB)
394_2017_1561_MOESM4_ESM.tif (5.5 mb)
Online resource 4: Effect of CRX and its combination with IMOs on lipid metabolism. Mice were fed either with NPD or HFD for 12 weeks. CRX (200 mg/kg) and its combination with IMOs (1 g/kg) were administered per orally to mice fed on HFD. A–D) serum lipid parameters (n= 5 – 6); E) expression of key lipid metabolism genes in vWAT (n=5); F–I) liver lipid parameters (n=5); J) expression of key lipid metabolism genes in liver (n=5); K) representative photomicrographs of oil red-O stained muscle sections (scale=100 µm). Values are expressed as mean ± SEM. Intergroup variations were assessed by one way ANOVA followed by Tukey’s multiple comparison test. * P < 0.05 versus NPD, ** P < 0.01 versus NPD, *** P < 0.001 versus NPD, # P < 0.05 versus HFD, ## P < 0.01 versus HFD, ### P < 0.001 versus HFD, † P < 0.05 versus HFD + CRX (TIF 5650 KB)
394_2017_1561_MOESM5_ESM.tif (175 kb)
Online resource 5: Effect of CRX and its combination with IMOs on feeding behaviour and activity. Mice were fed either with NPD or HFD for 12 weeks. CRX (200 mg/kg) and its combination with IMOs (1 g/kg) were administered per orally to mice fed on HFD. Average feed and water intake and urine output was measured in metabolic cages (n=4 mice/cage and n= 10 mice/group). Total locomotor activity (rearing plus ambulatory movement) was measured in a photoactometer. All the measurements were taken thrice in a month and average values are presented with SEM. Two-way ANOVA followed by Tukey’s post-hoc test was applied to asses any intergroup variations. * P < 0.05 versus NPD, *** P < 0.001 versus NPD, # P < 0.05 versus HFD, ## P < 0.01 versus HFD (TIF 174 KB)

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Food and Nutrition Biotechnology DivisionNational Agri-Food Biotechnology Institute (NABI)MohaliIndia
  2. 2.Pharmacology Division, University Institute of Pharmaceutical Sciences (UIPS)Panjab UniversityChandigarhIndia
  3. 3.Lundberg Laboratory for Diabetes Research, Department of Molecular and Clinical MedicineUniversity of Gothenburg, Sahlgrenska University HospitalGothenburgSweden
  4. 4.Department of Pharmaceutical and Pharmacological ScienceKatholieke Universiteit LeuvenLeuvenBelgium
  5. 5.Department of BiotechnologyGovernment College for GirlsChandigarhIndia
  6. 6.Functional Foods Research LaboratoryUniversity of Southern QueenslandToowoombaAustralia

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