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Changes in gut microbiota in response to a plant-based diet are related to changes in weight, body composition and insulin sensitivity: A 16-week randomized clinical trial. Hana Kahleova 1 , Emilie Rembert 1 , Jihad Alwarith, 1 Willy Yonas, 1 Andrea Tura, 2 Richard Holubkov, 3 and Neal Barnard 1,4 1. Physicians Committee for Responsible Medicine, Washington DC, USA • 2. Metabolic Unit, CNR Institute of Neuroscience, Padua, Italy • 3. School of Medicine, University of Utah, Salt Lake City, UT, USA • 4. Adjunct faculty, George Washington University School of Medicine and Health Sciences, Washington, DC, USA. Participants (n=148) were randomized to follow a low-fat vegan diet (n=73) or to make no diet changes (n=75) for 16 weeks. Gut microbiota composition was assessed, using uBiome kits. Dual energy X-ray absorptiometry was used to measure body composition. PREDIM index was used to assess insulin sensitivity. Repeated measure ANOVA was used for statistical analysis. Background Gut microbiota play an important role in weight management and metabolic health A plant-based diet may significantly change the gut microbiome composition The aim of this study was to test the effect of a 16-week plant-based dietary intervention on gut microbiota composition, body weight, body composition, and insulin sensitivity in overweight adults with no history of diabetes. Methods Baseline characteristics of the Study Population Data are means ± SD, or number (%). P-values refer to t-tests for continuous variables and χ2 for categorical variables. Body weight C V *** -5.8 kg (12.8 lb) ns *** 80 82 84 86 88 90 92 94 96 98 100 0 16 Weight (kg) Week Fat mass C V *** -3.9 kg ns *** 30 32 34 36 38 40 42 44 46 0 16 Fat mass (kg) Week Visceral Fat ** -172 cm 3 C V ns *** 1000 1100 1200 1300 1400 1500 1600 1700 1800 1900 2000 0 16 Visceral fat (cm 3 ) Week Insulin sensitivity C V ns *** *** +0.9 (+0.5 to +1.2) 1.6 2.1 2.6 3.1 3.6 4.1 4.6 5.1 5.6 0 16 PREDIM (mg/min/kg) Week C V ns * 20 25 30 35 40 45 0 16 Bacteroidetes (%) Week Bacteroidetes Firmicutes: Bacteroidetes C V ns ns 0 1 2 3 4 5 6 0 16 Firmicutes: Bacteroides Week Faecalibacterium prausnitzii C V * * *** +4.8 (+2.0 to +7.6) 1.6 2.6 3.6 4.6 5.6 6.6 7.6 8.6 9.6 10.6 11.6 0 16 Faecalium prausnitzii (%) Week Bacteroides fragilis C V *** *** *** +19.5 (+14.7 to +24.3) 0 5 10 15 20 25 30 35 0 16 Bacteroides fragilis (%) Week Body weight was reduced significantly in the vegan group (treatment effect -5.8 kg [95% CI, -6.9 to -4.7 kg]; p<0.001), particularly due to a reduction in fat mass (treatment effect -3.9 kg [95% CI, -4.6 to -3.1 kg]; p<0.001) and in visceral fat (treatment effect -172 cm 3 [95% CI, -308 to -37 kg]; p=0.01). PREDIM increased significantly (p<0.001) in the vegan group (treatment effect +0.88 [95% CI, +0.5 to +1.2]; p<0.001). The relative abundance of Faecalibacterium prausnitzii increased in the vegan group (treatment effect +4.8% [95% CI, +1.97 to +7.58%]; p=0.001). Relative changes in Faecalibacterium prausnitzii correlated negatively with changes in body weight (r=-0.26; p=0.008), fat mass (r=-0.26; p=0.008), and visceral fat (r=-0.25; p=0.01). The relative abundance of Bacteoides fragilis increased in the vegan group (treatment effect +19.5% [95% CI, +14.7 to +24.3%]; p<0.001). Relative changes in Bacteroides Fragilis correlated negatively with changes in body weight (r=-0.48; p<0.001), fat mass (r=-0.48; p<0.001), visceral fat (r=-0.24; p=0.02), and positively with changes in PREDIM (r=0.36; p=0.0004). Results A 16-week low-fat vegan dietary intervention induced changes in gut microbiota that were related to changes in weight, body composition and insulin sensitivity in overweight adults. Conclusions Trial registration: ClinicalTrials.gov number, NCT02939638 Funding: This work was funded by the Physicians Committee for Responsible Medicine. Characteristic Vegan group (n=73) Control group (n=74) Statistic Age (years) 53.6 ± 12.1 57.6 ± 10.3 P=0.027 Sex (number, %) Male 13 (17.8) 7 (9.5) P=0.14 Female 60 (82.2) 67 (90.5) BMI (kg/m 2 ) 32.6 ± 3.8 33.4 ± 3.6 P=0.31 Race, (number, %) White 36 (49.3) 39 (52.7) P=0.34 Black 36 (49.3) 31 (41.9) Asian, Pacific Islander 0 2 (2.7) N/A - did not disclose 1 (1.4) 2 (2.7) Figure 2. Correlations between changes in relative abundance of gut bacteria and changes in metabolic outcomes: Correlations between changes in relative abundance of Faecalibacterium prausnitzii and changes in body weight (A), fat mass (B), and visceral fat (C); and correlations between changes in relative abundance of Bacteroides fragilis and changes in body weight (D), fat mass (E), visceral fat (F), and insulin sensitivity (G). G F E D C B A

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Page 1: Changes in gut microbiota in response to a plant-based diet ...Changes in gut microbiota in response to a plant-based diet are related to changes in weight, body composition and insulin

Changes in gut microbiota in response to a plant-based diet are related to changes in weight, body composition and insulin sensitivity: A 16-week randomized clinical trial. Hana Kahleova1, Emilie Rembert1, Jihad Alwarith,1 Willy Yonas,1 Andrea Tura,2 Richard Holubkov,3 and Neal Barnard1,4

1. Physicians Committee for Responsible Medicine, Washington DC, USA • 2. Metabolic Unit, CNR Institute of Neuroscience, Padua, Italy • 3. School of Medicine, University of Utah, Salt Lake City, UT, USA • 4. Adjunct faculty, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.

Participants (n=148) were randomized to follow a low-fat vegan diet (n=73) or to make no diet changes (n=75) for 16 weeks.

Gut microbiota composition was assessed, using uBiome kits.

Dual energy X-ray absorptiometry was used to measure body composition.

PREDIM index was used to assess insulin sensitivity.

Repeated measure ANOVA was used for statistical analysis.

Background Gut microbiota play an important role in weight management and metabolic health

A plant-based diet may significantly change the gut microbiome composition

The aim of this study was to test the effect of a 16-week plant-based dietary intervention on gut microbiota composition, body weight, body composition, and insulin sensitivity in overweight adults with no history of diabetes.

Methods

Baseline characteristics of the Study Population Data are means ± SD, or number (%). P-values refer to t-tests for continuous variables and χ2 for categorical variables.

Body weight

C

V***

-5.8 kg (12.8 lb)

ns

***

80828486889092949698

100

0 16W

eig

ht

(kg

)Week

Fat mass

C

V***

-3.9 kg

ns

***

30

32

34

36

38

40

42

44

46

0 16

Fat

mas

s (k

g)

Week

Visceral Fat

**

-172 cm3

C

V

ns

***

10001100120013001400150016001700180019002000

0 16

Vis

cera

l fa

t (c

m3)

Week

Insulin sensitivity

C

V

ns

******

+0.9 (+0.5 to +1.2)

1.6

2.1

2.6

3.1

3.6

4.1

4.6

5.1

5.6

0 16

PR

ED

IM (

mg

/min

/kg

)

Week

CV

ns

*

20

25

30

35

40

45

0 16

Bac

tero

idet

es (

%)

Week

BacteroidetesFirmicutes: Bacteroidetes

CV

ns

ns

0

1

2

3

4

5

6

0 16

Fir

mic

ute

s:

Bac

tero

ides

Week

Faecalibacterium prausnitzii

C

V

*

****

+4.8 (+2.0 to +7.6)

1.62.63.64.65.66.67.68.69.6

10.611.6

0 16

Fa

ec

aliu

m p

rau

sn

itzi

i (%

)

Week

Bacteroides fragilisC

V

***

***

***

+19.5 (+14.7 to +24.3)

0

5

10

15

20

25

30

35

0 16

Bac

tero

ides

fra

gil

is (

%)

Week

Body weight was reduced significantly in the vegan group (treatment effect -5.8 kg [95% CI, -6.9 to -4.7 kg]; p<0.001), particularly due to a reduction in fat mass (treatment effect -3.9 kg [95% CI, -4.6 to -3.1 kg]; p<0.001) and in visceral fat (treatment effect -172 cm3 [95% CI, -308 to -37 kg]; p=0.01). PREDIM increased significantly (p<0.001) in the vegan group (treatment effect +0.88 [95% CI, +0.5 to +1.2]; p<0.001). The relative abundance of Faecalibacterium prausnitzii increased in the vegan group (treatment effect +4.8% [95% CI, +1.97 to +7.58%]; p=0.001). Relative changes in Faecalibacterium prausnitzii correlated negatively with changes in body weight (r=-0.26; p=0.008), fat mass (r=-0.26; p=0.008), and visceral fat (r=-0.25; p=0.01). The relative abundance of Bacteoides fragilis increased in the vegan group (treatment effect +19.5% [95% CI, +14.7 to +24.3%]; p<0.001). Relative changes in Bacteroides Fragilis correlated negatively with changes in body weight (r=-0.48; p<0.001), fat mass (r=-0.48; p<0.001), visceral fat (r=-0.24; p=0.02), and positively with changes in PREDIM (r=0.36; p=0.0004).

Results

ConclusionsA 16-week low-fat vegan dietary intervention induced changes in gut microbiota that were related to changes in weight, body composition and insulin sensitivity in overweight adults.

Conclusions Trial registration: ClinicalTrials.gov number, NCT02939638

Funding: This work was funded by the Physicians Committee for Responsible Medicine.

Characteristic Vegan group (n=73) Control group (n=74) Statistic

Age (years) 53.6 ± 12.1 57.6 ± 10.3 P=0.027

Sex (number, %) Male 13 (17.8) 7 (9.5) P=0.14

Female 60 (82.2) 67 (90.5)

BMI (kg/m2) 32.6 ± 3.8 33.4 ± 3.6 P=0.31

Race, (number, %) White 36 (49.3) 39 (52.7) P=0.34

Black 36 (49.3) 31 (41.9)

Asian, Pacific Islander 0 2 (2.7)

N/A - did not disclose 1 (1.4) 2 (2.7)

Figure 2. Correlations between changes in relative abundance of gut bacteria and changes in metabolic outcomes: Correlations between changes in relative abundance of Faecalibacterium prausnitzii and changes in body weight (A), fat mass (B), and visceral fat (C); and correlations between changes in relative abundance of Bacteroides fragilis and changes in body weight (D), fat mass (E), visceral fat (F), and insulin sensitivity (G).

GFEDCBA