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



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.


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.


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.


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


Butyrate Cranberry extract Ectopic fat Isomalto-oligosaccharides Polyphenols Mucin 



Acetyl-CoA carboxylase


Acyl-coenzyme A oxidase 1


Akkermansia muciniphila


Anaerostipes butyraticus




Bacteroides sp.




Butyricicoccus pullicaecorum


Butyrivibrio sp.


CCAAT/enhancer-binding protein alpha


Citrobacter sp.




Clostridium sp.


Clostridium propionicum


Cranberry extract


Escherichia coli


Enterobacter sp.




Eubacterium sp.


Fatty acid synthase


Faecalibacterium sp.


Free fatty acid receptors






Clostridium coccoides group




Glycogen synthase-2


High-fat diet


Homeostasis model assessment


Hormone sensitive lipase




Klebsiella sp.


Lactobacillus sp.






Macrophagic chemoattractant protein-1




Myeloid differentiation primary response gene 88


Nonesterified fatty acids


Nuclear factor kappa beta


Normal pellet diet/ normal chow


Phosphoenolpyruvate carboxykinase


Peroxisome proliferator-activated receptor


Prevotella sp.


Relative humidity


Roseburia sp.


Short chain fatty acids


Segmented filamentous bacteria


Suppressor of cytokine signalling 3


Toll like receptors


Tumor necrosis factor-α


Visceral white adipose tissue


Zona occludens



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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