artificial sweeteners induce glucose intolerance by altering the gut microbiota. jotham suez, tal...

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Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph A. Thaiss, Ori Maza, David Israeli, Niv Zmora, Shlomit Gilad, Adina Weinberger, Yael Kuperman, Alon Harmelin, Ilana Kolodkin-Gal, Hagit Shapiro, Zamir Halpern, Eran Segal & Eran Elinav Nature 9 October 2014 vol 514 p181-186.

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Page 1: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Artificial sweeteners induce glucose intolerance by altering the gut

microbiota.Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira,

Christoph A. Thaiss, Ori Maza, David Israeli, Niv Zmora, Shlomit Gilad, Adina Weinberger, Yael Kuperman, Alon Harmelin, Ilana Kolodkin-Gal, Hagit Shapiro, Zamir Halpern, Eran Segal & Eran

Elinav

Nature 9 October 2014 vol 514 p181-186.

Page 2: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Saccharine

Page 3: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Sucralose

Page 4: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph
Page 5: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Chronic NAS consumption exacerbates glucose tolerance.

Page 6: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph
Page 7: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Glucose tolerance test: (40 mg glucose orally/mouse):

Page 8: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Extended data Figure 1.

Page 9: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Fig. 1a

Page 10: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Two-way ANOVA

Page 11: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Fig. 1b

(Area Under Two-hour Curve)

Page 12: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Extended data Figure 1.

Page 13: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Fig. 1c

Page 14: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Extended data Figure 2a.

Page 15: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Extended data Figure 1.

Page 16: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Fig. 1d

Page 17: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Extended data Figure 2b.

Page 18: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Extended data Figure 1.

Page 19: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Extended data Figure 2c.

Page 20: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Extended data Figure 2d.

Page 21: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Gut microbiota mediates NAS-induced glucose intolerance.

Page 22: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Ciprofloxacin: fluoroquinolone (inhibition of DNA gyrase. Gram-negative bacteria and gram-positiv e cocci.

Page 23: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Metronidazole (Flagyl): used against anaerobic bacteria and protozoa. Inhibits DNA synthesis in the reduced form (anaerobic conditions).

Page 24: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Vancomycin: protein inhibition.Active against gram-positive bacteria.

Page 25: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Extended data Figure 1.

Page 26: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Fig. 1a

Page 27: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Fig. 1b

(Area Under Two-hour Curve)

Page 28: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Fig. 1d

Page 29: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Extended data Figure 1.

Page 30: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Fig. 1e

Page 31: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Extended data Figure 2e.

Page 32: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Fig. 1f

Page 33: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Extended data Figure 2f.

Page 34: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

NAS mediate distinct functional alterations to the microbiotia.

Page 35: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

We matched all OTUs to its phylogenetic affiliation, and used this information to generate a principal component analysis (PCA) that is based on the presence and absence of individual OTUs in individual samples. A total of 27 dimensions were used to account for the total variance. The first two dimensions PC1 and PC2, which accounted for 29.6% of the total variance did not show an apparent correlation to the eczema status of the infants (Figure 4A). The first dimension (21.6%) was correlated to age, suggesting that the ageing process was a relatively domineering factor that mediated changes in microbial richness and diversity among infants.

Page 36: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Fig. 1G

Page 37: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Fig. 1H

Page 38: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Extended data Figure 6.

(1) Saccharin / sucrose(2) Saccharin / water(3) Saccharin / glucose(4) FT: Saccharin / glucose

Page 39: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Fig. 2a

Page 40: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Extended data Figure 6.

Page 41: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Fig. 2b

Page 42: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Fig. 2c

Page 43: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Fig. 2d

Page 44: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Fig. 2e

Page 45: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Fig. 2gh

Page 46: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Extended data Figure 6.

(1) Saccharin / sucrose(2) Saccharin / water(3) Saccharin / glucose(4) FT: Saccharin / glucose

Page 47: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Extended data Figure 7c.

Page 48: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Extended data Figure 7d.

Page 49: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

NAS directly modulate the microbiota to induce glucose intolerance.

Page 50: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph
Page 51: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph
Page 52: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph
Page 53: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

16 S ribosomal RNA

Page 54: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Taxonomic Microbiota Analysis:Barcoded primers:

Page 55: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Extended data Figure 5a.

Page 56: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Extended data Figure 5b.

Page 57: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Extended data Figure 5c.

Page 58: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph
Page 59: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph
Page 60: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph
Page 61: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Extended data Figure 8a.

Page 62: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Extended data Figure 8b.

Page 63: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Fig. 3a

Page 64: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Extended data Figure 8c.

Page 65: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Fig. 3b

Page 66: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Fig. 3c

Page 67: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

NAS in humans asociate with impaired glucose intolerance.

Page 68: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Fig. 4a

Page 69: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Extended data Figure 9a.

Page 70: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Fig. 4b

Page 71: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Fig. 4c,d

Page 72: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Extended data Figure 9b.

Page 73: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph

Suez Jotham et al. (2014) Fig. 4e

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Suez Jotham et al. (2014) Fig. 4f

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Suez Jotham et al. (2014) Fig. 4g,h