Table 1 Characteristics of the included observational studies

1

Gutierrez-Diaz (2016) [17]

cohort

31

Italy

Healthy individual without any PMH, and no DH in the past 6 months.

mean age: 42.1 y; 8M, 24F

BMI: 26

16S rRNA sequencing

↑ Bacteroidetes (p=0.001)

↑ Prevotella (p=0.003)

↑ Prevotellacea (p=0.002)

↓ Firmicutes (p=0.003)

↓ Lachnospiraceae (p=0.045)

NA

NA

↑ Cereals

↑ Legumes

↑ Vegetable

↑fruits

↑monosaturated to saturated ratio

\(\to\) ethanol

↓ meat

↓ milk

MS; HLPC; GC; CE

faecal propionate (p=0.034)

fecal butyrate (p=0.018)

• (0-8) points Trichopoulou MDS

• FFQ

2

Gutierrez-Diaz (2017) [22]

Cross-sectional

74

Spain

Healthy individual >50 years without any PMH, and no DH (including probiotics) in the past month,

mean age: 71.3 y

20M, 54F

16S rRNA sequencing

↑ Clostridium cluster XIVa (p=0.016)

\(\uparrow\) Faecalibacterium (p=0.006)

NA

NA

↑ Cereals

↑ Legumes

↑ Vegetable

↑fruits

↑monosaturated to saturated ratio

\(\to\) ethanol

↓ meat

↓ milk

MS; HLPC; GC; CE

↑ benzoic acid (p<0.05)

↑ 3-hydroxyphenylacetic acids (p<0.05);

No effect (p>0.05) on phenylacetic acid, phenylpropionic acid,

3-(3-hydroxyphenyl) propionic acid,

4 hydroxyphenyl acetic acid,

vanillic acid, syringic acid,

phthalic acid or γ-valerolactone.

• (0-8) points Trichopoulou MDS

• FFQ

3

Mitsou 2017 [1]

Cross-sectional

116

Greece

Healthy individual 18-65 years without any PMH, and no DH (including probiotics)

Mean age: 42 y

61M, 55F

BMI: 27

16S rRNA sequencing

↑ Bacteroides (p=0.011)

↓ Escherichia coli (p=0.022)

↓ Candida Albicans (p=0.039)

↑fecal moisture& defecation frequency

↓ bloating

NA

↑ non-refined

↑ cereals

↑ fruit

↑vegetables

↑ potatoes

↑ legumes

↑ olive oil

↑ fish

GC

↑ acetate (p=0.009)

↓ Caproic acid (p=0.045);

No effect (p>0.05) on total SCFA,

propionate, butyrate,

iso-butyrate, iso-valerate,

iso-caproic acid, valerate and

heptanoic acid

• Three tertiles (0-11 points)

• Panagiotakos classification MDS

• FFQ

4

Shankar2017 [23]

cohort

42

USA & Egypt

Healthy teenagers without any PMH, and no DH in the last 3 months (including probiotics);

28 Egypt (mean age: 13.9 y) received MD

14 U.S (mean age= 12.9 y) received western Diet

16S rRNA sequencing

↑ Prevotella (p<0.05)

↓ Bacterioides (p<0.05)

NA

Bray-Curtis beta diversity:

significant intersample dissimilarity

↑ fruits

↑vegetables

↑ whole grain

↑ beans

↑ nuts

↑ plant fats

↓ meats

↓ sweets

nuclear magnetic resonance

↑ SCFA (p<0.05)

(acetatae; butyrate; propionate)

• Not specified MDS

5

Bowyer 2018 [24]

cohort

2070

UK

mono- and dizygotic twins;

1863 F, 207 M

mean age: 60.5

mean BMI: 25.9

16S rRNA sequencing

↓ Ruminococcus (p<0.05)

↓ Lachnospira (p<0.05)

↓ Actinomyces (p<0.05)

NA

Beta-diversity: Weighted and Unweighted UniFrac distances/ significant distinction

Alpha diversity via Chao1, OTUs, Shannon, and Simpson./ Significant correlation of all alpha measures with at least one dietary measure.

NA

NA

NA

• (0-10) points classification MDS,

• FFQ

• Healthy eating index (HEI),

• Healthy food diversity (HFD)

6

Garcia-Mantrana 2018 [25]

cross- sectional

27

Spain

Healthy individuals without any PMH, and no DH in the last 2 months (including probiotics);

mean age: 39.5 y

16 F (mean BMI:21.95),

11M (mean BMI: 25.29)

16S rRNA sequencing

↑Christensenellaceae (p<0.05)

↓Streptococcaceae (p>0.05)

↑ Bifidobacteriae (p<0.05)

NA

Alpha diversity via Chao1 and Shannon./ no significant result in Shannon; but higher bacterial richness via Chao1in MD

NA

HPLC

↑ total SCFA (p=0.020)

↑ acetate (p=0.006)

↑ propionate (p=0.016)

(0-14) points classification MDS,

FFQ

PREDIMED test

7

Maskarinec 2019 [15]

Cohort

1735

USA

Japanese American, Latino, Hawaiians, and African Americans; Healthy;

858 M, 877F, mean age= 69 y

29.3% NL weight,

40.4% overweight, 30.3% obese

BMI= 28 [17.1-49.8]

16S rRNA sequencing

↓ Actinobacteria (p<0.05)

NA

Beta-diversity: Weighted and Unweighted UniFrac distances/ significant distinction

Alpha diversity via Shannon./ Linear trend in 4 dietary measure.

NA

NA

NA

(0-8) points Trichopoulou MDS

qFFQ

HEI

8

Cox 2020 [14]

cohort

296

USA and Turkey

200 M; 96 F;

Age: 58

BMI: 27

139 Turkish (46 healthy controls, 50 compensated & 43 decompensated cirrhotic; 79M, 60F) received MD

157 American (48 healthy controls, 59 compensated & 50 decompensated cirrhotic; 121M,36F) received western diet

16S rRNA sequencing

↑beneficial taxa

(Oscillibacter, Blautia) (p<0.05),

Altered diet‐microbial interactions could affect the 90‐day hospitalization risk

Alpha diversity via Shannon./ higher alpha diversity with MD adherence.

NA

nuclear magnetic resonance (NMR) spectroscopy

↑ plasma lactate (p<0.001)

Not specified MDS;

FFQ

9

Gallè 2020 [26]

Cross-sectional

140

Italy

Apparently healthy

68M, 72F

mean age :22.5 y

mean BMI:22.4

16S rDNA sequencing

↑ Firmicutes (p = 0.001)

↑ Bacteroidetes (p = 0.001)

↑ Lactobacillus(p=0.002)

↑ Lactococcus (p=0.01)

↓ Paraprevotella (p = 0.001)

↓Oscillospira (p = 0.001)

↓Ruminococcus (p = 0.001)

NA

Beta-diversity: Bray-Curtis/ significant distinction

Alpha diversity via Shannon./no significant association

NA

NA

NA

• (0-9) points Martínez-González MDS

• IPAQ

10

Maldonado-Contreras 2020 [32]

Cross-sectional

20

USA (Caribbean Latino)

Caribbean Latino from senior center with CVD with no antibiotic in last 6 months;

9 with T2DM

mean age: 62.7 y

mean BMI: 28.9

4M, 16F

16S rRNA sequencing

↑ Prevotella copri (p=0.001)

NA

Beta-diversity: Uni-Frac / significant association with some of dietary components.

Alpha diversity via Faith’s PD and Shannon./ significant correlation between Shannon and total HEI-2015 score; no significant association between Faith’s PD and total HEI-2015 score

↑fruit

↑vegetables

↓seafood protein

↓total protein

MS

↓Acetate in MDS (p=0.04)

↓ butyrate in MDS (0.03)

↑Acetate in HEI (p=0.06)

↑ propionate in HEI (0.02)

• (0-9) points Trichopoulou MDS

• HEI

• FFQ

• DAS-28

11

Ruiz-Saavedra 2020 [27]

cross-sectional

73

Spain

Healthy individuals without any PMH, and no DH in the last 2 months (including probiotics)

20 M, 53 F

BMI:19.9-37.5

Age:56-95

PCR

↑Faecalibacterium. Prausnitzii (p<0.05)

↓ Lactobacillus. Spp (p<0.05)

↓ serum IL-8

NA

NA

Gas chromatography

↑ SCFA (p-value<0.05)

• (0-9) points Trichopoulou MDS

• FFQ

• DII

• EDII

• HEI

• AHEI

• DQI-I

• MMDS

• rMDS

12

Valeriani 2020 [28]

Cross- sectional

59

Italy (Caucasian)

Healthy individuals without any PMH, and no DH in the last 3 months;

mean BMI:22

mean age:23 y

29M, 30F

16S rRNA sequencing

↑Firmicutes (p>0.05)

↓Bacteroidetes (p>0.05)

NA

NA

NA

NA

NA

• (0-9) points Martínez-González MDS

• IPAQ

13

Rosés 2021 [29]

Cohort

360

Spain

Healthy individual without PMH and DH with BMI:25-40;

251F, 109 M

mean age: 45.0 y

mean BMI: 28.8

16S rRNA sequencing

↑Oscillibacter valericigenes (p<0.001)

↑Oscillospira (Flavonifractor) plautii (p<0.001)

↑Roseburia faecis (p<0.001)

↑Ruminococcus bromii (p=0.01)

↑Butyricicoccus pullicaecorum (p<0.001)

↑Papillibacter cinnamivorans (p=0.04)

↑ Bifidobacterium animalis (p<0.001)

NA

Beta-diversity: Bray-Curtis/ no significant correlation with MD adherence.

Alpha diversity via Shannon./no significant correlation with MD adherence.

↑ Fiber

↑ Legumes

↑Vegetables

↑ fruit

↑ olive oil

↑ nuts

Reconstructive method by Kegg

↑SCFA (p-value: N/A) (SCFAs were not directly quantified via fecal/blood samples. They were assessed indirectly through other biomarkers, such as K0)

• (0-14) points classification MDS;

• FFQ including 137 food items with corresponding portion size,

• PREDIMED 14-item questionnaire

14

Wang 2021 [30]

prospective

307

USA

Healthy at baseline

Age:45-80 y

307M

16sr RNA sequencing

↑ Eubacterium eligens (p<0.05)

↑ Faecalibacterium prausnitzii (p<0.05)

↑ Bacteroides cellulosilyticus (p<0.05)

↓ Clostridium leptum (p<0.05)

↓Collinsella aerofaciens (p<0.05)

↓ Ruminococcus torques (p<0.05)

NA

Beta-diversity: Bray-Curtis/ no significant correlation with MD adherence.

Alpha diversity via Shannon./no significant correlation with MD adherence

↑vegetables↑legumes, ↑fruit,

↑nuts, ↑whole grains, ↓red/processed meat,

↑fish, ↓alcohol

↑ ratio of monounsaturated to saturated fat.

NA

↑SCFA

(p-value: N/A)

• (0-9) points Trichopoulou MDS;

• FFQ

• MD index; Med-diet

15

Turpin 2022 [31]

cohort

2289

Canada

Healthy first-degree relatives of patients with Crohn’s disease;

Median age: 18

1083 M, 1206 F

Stool analysis (not specified)

↑Ruminococcus (p<0.05)

↑Faecalibacterium (p<0.05)

NA

NA

↑fruits, ↑vegetables, ↑plant proteins,

↑whole grains

↑low-calorie starches

↑low-fat or no-fat dairy

content

↑milk alternatives

NA

NA

• (0-14) points MDS

• FFQ

16

De Filippis 2015 [11]

cohort

153

Italy

Apparently healthy volunteers

comprising 51 vegetarians, 51 vegans and 51 omnivores;

Age: 27-47;

BMI: 22

16S rRNA sequencing

↑ Prevotella (p<0.01)

↑ Lachnospira (p<0.01)

↓ L-Ruminococcus (p<0.001)

NA

Beta-diversity: Uni-Frac / no significant correlation with MD adherence.

Alpha diversity via not-determined method./no significant correlation

↑cereals, ↑fruit, ↑vegetable ↑legumes

GC-MS

↑ total SCFA (p<0.05)

↑Acetate (p<0.05)

↑ Propionate (p<0.05)

• (0-9) points Trichopoulou MDS;

17

Calabrese 2023 [33]

Cohort

46

Italy

46 moderate to severe NAFLD patients; BMI \(\ge\) 25; Age>30 and <60; two groups: Only physical activity and physical activity+MedDiet;

16S rRNA sequencing

↑Peptococcaceae(p<0.05)

↑Rikenellaceae (p<0.05)

↑Oscillospiraceae(p<0.05)

↑Ruminococcaceae (p<0.05)

↑Lachnospiraceae (p<0.05)

↑Haemophilus (p<0.05)

↑Sanguibacteroides (p<0.05)

↑Catenibactrium (p<0.05)

Better DM/hyperlipidemic state control

NA

saturated fats \(\le\) 10% of total daily calories

GC-MS

↓Butanoic Acid (p<0.05)

↓Pentanoic Acid (p<0.05)

↓Heptanoic Acid (p<0.05)

• FFQ