Intestinal Dysbiosis Contributes to the Delayed Gastrointestinal Transit in High-Fat Diet Fed Mice

Mallappa Anitha, François Reichardt, Sahar Tabatabavakili, Behtash Ghazi Nezami, Benoit Chassaing, Simon Mwangi, Matam Vijay Kumar, Andrew Gewirtz, Shanthi Srinivasan

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Background & Aims: High-fat diet (HFD) feeding is associated with gastrointestinal motility disorders. We recently reported delayed colonic motility in mice fed a HFD for 11 weeks. In this study, we investigated the contributing role of gut microbiota in HFD-induced gut dysmotility. Methods: Male C57BL/6 mice were fed a HFD (60% kcal fat) or a regular/control diet (RD) (18% kcal fat) for 13 weeks. Serum and fecal endotoxin levels were measured, and relative amounts of specific gut bacteria in the feces were assessed by real-time polymerase chain reaction. Intestinal transit was measured by fluorescent-labeled marker and a bead expulsion test. Enteric neurons were assessed by immunostaining. Oligofructose (OFS) supplementation with RD or HFD for 5 weeks also was studied. In vitro studies were performed using primary enteric neurons and an enteric neuronal cell line. Results: HFD-fed mice had reduced numbers of enteric nitrergic neurons and showed delayed gastrointestinal transit compared with RD-fed mice. HFD-fed mice had higher fecal Firmicutes and Escherichia coli and lower Bacteroidetes compared with RD-fed mice. OFS supplementation protected against enteric nitrergic neuron loss in HFD-fed mice, and improved intestinal transit time. OFS supplementation resulted in a reduction in fecal Firmicutes and Escherichia coli and serum endotoxin levels. In vitro, palmitate activation of TLR4 induced enteric neuronal apoptosis in a Phospho-c-Jun N-terminal kinase-dependent pathway. This apoptosis was prevented by a c-Jun N-terminal kinase inhibitor and in neurons from TLR4-/- mice. Conclusions: Together our data suggest that intestinal dysbiosis in HFD-fed mice contribute to the delayed intestinal motility by inducing a TLR4-dependent neuronal loss. Manipulation of gut microbiota with OFS improved intestinal motility in HFD mice.

Original languageEnglish (US)
Pages (from-to)328-339
Number of pages12
JournalCMGH
Volume2
Issue number3
DOIs
StatePublished - May 1 2016

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Dysbiosis
Gastrointestinal Transit
High Fat Diet
Gastrointestinal Motility
Nitrergic Neurons
Diet
JNK Mitogen-Activated Protein Kinases
Neurons
Fats
Apoptosis
Bacteroidetes
Palmitates
Serum
Inbred C57BL Mouse
Endotoxins
Feces
Real-Time Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

Anitha, M., Reichardt, F., Tabatabavakili, S., Nezami, B. G., Chassaing, B., Mwangi, S., ... Srinivasan, S. (2016). Intestinal Dysbiosis Contributes to the Delayed Gastrointestinal Transit in High-Fat Diet Fed Mice. CMGH, 2(3), 328-339. https://doi.org/10.1016/j.jcmgh.2015.12.008
Anitha, Mallappa ; Reichardt, François ; Tabatabavakili, Sahar ; Nezami, Behtash Ghazi ; Chassaing, Benoit ; Mwangi, Simon ; Kumar, Matam Vijay ; Gewirtz, Andrew ; Srinivasan, Shanthi. / Intestinal Dysbiosis Contributes to the Delayed Gastrointestinal Transit in High-Fat Diet Fed Mice. In: CMGH. 2016 ; Vol. 2, No. 3. pp. 328-339.
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Anitha, M, Reichardt, F, Tabatabavakili, S, Nezami, BG, Chassaing, B, Mwangi, S, Kumar, MV, Gewirtz, A & Srinivasan, S 2016, 'Intestinal Dysbiosis Contributes to the Delayed Gastrointestinal Transit in High-Fat Diet Fed Mice', CMGH, vol. 2, no. 3, pp. 328-339. https://doi.org/10.1016/j.jcmgh.2015.12.008

Intestinal Dysbiosis Contributes to the Delayed Gastrointestinal Transit in High-Fat Diet Fed Mice. / Anitha, Mallappa; Reichardt, François; Tabatabavakili, Sahar; Nezami, Behtash Ghazi; Chassaing, Benoit; Mwangi, Simon; Kumar, Matam Vijay; Gewirtz, Andrew; Srinivasan, Shanthi.

In: CMGH, Vol. 2, No. 3, 01.05.2016, p. 328-339.

Research output: Contribution to journalArticle

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T1 - Intestinal Dysbiosis Contributes to the Delayed Gastrointestinal Transit in High-Fat Diet Fed Mice

AU - Anitha, Mallappa

AU - Reichardt, François

AU - Tabatabavakili, Sahar

AU - Nezami, Behtash Ghazi

AU - Chassaing, Benoit

AU - Mwangi, Simon

AU - Kumar, Matam Vijay

AU - Gewirtz, Andrew

AU - Srinivasan, Shanthi

PY - 2016/5/1

Y1 - 2016/5/1

N2 - Background & Aims: High-fat diet (HFD) feeding is associated with gastrointestinal motility disorders. We recently reported delayed colonic motility in mice fed a HFD for 11 weeks. In this study, we investigated the contributing role of gut microbiota in HFD-induced gut dysmotility. Methods: Male C57BL/6 mice were fed a HFD (60% kcal fat) or a regular/control diet (RD) (18% kcal fat) for 13 weeks. Serum and fecal endotoxin levels were measured, and relative amounts of specific gut bacteria in the feces were assessed by real-time polymerase chain reaction. Intestinal transit was measured by fluorescent-labeled marker and a bead expulsion test. Enteric neurons were assessed by immunostaining. Oligofructose (OFS) supplementation with RD or HFD for 5 weeks also was studied. In vitro studies were performed using primary enteric neurons and an enteric neuronal cell line. Results: HFD-fed mice had reduced numbers of enteric nitrergic neurons and showed delayed gastrointestinal transit compared with RD-fed mice. HFD-fed mice had higher fecal Firmicutes and Escherichia coli and lower Bacteroidetes compared with RD-fed mice. OFS supplementation protected against enteric nitrergic neuron loss in HFD-fed mice, and improved intestinal transit time. OFS supplementation resulted in a reduction in fecal Firmicutes and Escherichia coli and serum endotoxin levels. In vitro, palmitate activation of TLR4 induced enteric neuronal apoptosis in a Phospho-c-Jun N-terminal kinase-dependent pathway. This apoptosis was prevented by a c-Jun N-terminal kinase inhibitor and in neurons from TLR4-/- mice. Conclusions: Together our data suggest that intestinal dysbiosis in HFD-fed mice contribute to the delayed intestinal motility by inducing a TLR4-dependent neuronal loss. Manipulation of gut microbiota with OFS improved intestinal motility in HFD mice.

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Anitha M, Reichardt F, Tabatabavakili S, Nezami BG, Chassaing B, Mwangi S et al. Intestinal Dysbiosis Contributes to the Delayed Gastrointestinal Transit in High-Fat Diet Fed Mice. CMGH. 2016 May 1;2(3):328-339. https://doi.org/10.1016/j.jcmgh.2015.12.008