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.

Saccharine

Sucralose

Chronic NAS consumption exacerbates glucose tolerance.

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

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

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

Two-way ANOVA

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

(Area Under Two-hour Curve)

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

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

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

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

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

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

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

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

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

Gut microbiota mediates NAS-induced glucose intolerance.

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

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

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

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

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

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

(Area Under Two-hour Curve)

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

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

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

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

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

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

NAS mediate distinct functional alterations to the microbiotia.

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.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

NAS directly modulate the microbiota to induce glucose intolerance.

16 S ribosomal RNA

Taxonomic Microbiota Analysis:Barcoded primers:

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

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

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

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

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

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

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

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

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

NAS in humans asociate with impaired glucose intolerance.

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

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

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

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

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

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

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

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