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Randomized Controlled Trial
. 2021 Jul 30;13(8):2638.
doi: 10.3390/nu13082638.

Differential Effects of Western and Mediterranean-Type Diets on Gut Microbiota: A Metagenomics and Metabolomics Approach

Claudia Barber  1   2 , Marianela Mego  1   2 , Carlos Sabater  3   4 , Fernando Vallejo  5 , Rogger Alvaro Bendezu  1   2 , Marcela Masihy  1   2 , Francisco Guarner  1   2 , Juan Carlos Espín  6 , Abelardo Margolles  3   4 , Fernando Azpiroz  1   2
Affiliations
Randomized Controlled Trial

Differential Effects of Western and Mediterranean-Type Diets on Gut Microbiota: A Metagenomics and Metabolomics Approach

Claudia Barber et al. Nutrients. .

Abstract

Our aim was to determine the effect of diet on gut microbiota, digestive function and sensations, using an integrated clinical, metagenomics and metabolomics approach. We conducted a cross-over, randomised study on the effects of a Western-type diet versus a fibre-enriched Mediterranean diet. In 20 healthy men, each diet was administered for 2 weeks preceded by a 2-week washout diet. The following outcomes were recorded: (a) number of anal gas evacuations; (b) digestive sensations; (c) volume of gas evacuated after a probe meal; (d) colonic content by magnetic resonance imaging; (e) gut microbiota taxonomy and metabolic functions by shotgun sequencing of faecal samples; (f) urinary metabolites using untargeted metabolomics. As compared to a Western diet, the Mediterranean diet was associated with (i) higher number of anal gas evacuations, (ii) sensation of flatulence and borborygmi, (iii) larger volume of gas after the meal and (iv) larger colonic content. Despite the relatively little difference in microbiota composition between both diets, microbial metabolism differed substantially, as shown by urinary metabolite profiles and the abundance of microbial metabolic pathways. The effects of the diet were less evident in individuals with robust microbiotas (higher beta-diversity). To conclude, healthy individuals tolerate dietary changes with minor microbial modifications at the composition level but with remarkable variation in microbial metabolism.

Keywords: Mediterranean-type diet; Western-type diet; digestive sensations; gut microbiota; intestinal gas; metabolomics; metagenomics.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Experimental design. Cross-over, randomised study; 20 participants were included and 18 adhered to study instructions and were included for analysis.
Figure 2
Figure 2
(A) Sensations measured by daily questionnaires during the last 2 days of the evaluation periods (n = 18). Data are average of 2 consecutive days. (B) Physiological parameters measured during the last 2 days of the evaluation periods. Values of number of daytime anal gas evacuations, number of bowel movements, Bristol stool form scale and faecal weight are average of 2 consecutive days; volume of gas evacuated during 4 h after a probe meal, and colonic content measured only once (n = 18).
Figure 2
Figure 2
(A) Sensations measured by daily questionnaires during the last 2 days of the evaluation periods (n = 18). Data are average of 2 consecutive days. (B) Physiological parameters measured during the last 2 days of the evaluation periods. Values of number of daytime anal gas evacuations, number of bowel movements, Bristol stool form scale and faecal weight are average of 2 consecutive days; volume of gas evacuated during 4 h after a probe meal, and colonic content measured only once (n = 18).
Figure 3
Figure 3
(A) Taxonomic clades more abundant in samples after Fibre-Enriched Mediterranean-Type Diet (FMD) intervention. Agathobaculum and Anaerostipes genus as well as Agathobaculum butyriciproducens and Anaerostipes hadrus species showed significantly higher (p < 0.05) abundances, assessed by DESeq2 differential abundance testing, in FMD samples. (B) Differential profiles obtained for Western-Type Diet (WD) and FMD samples through multi-omic data integration of metabolic profiles and metabolic pathways determined by shotgun sequencing using DIABLO biomarker discovery pipeline. (C) Variable importance coefficients obtained in DIABLO pipeline for metabolites and microbial pathways in WD and FMD interventions. TMAO: Trimethylamine N-oxide. PWY-7222: guanosine deoxyribonucleotides de novo biosynthesis. PWY-3841: folate transformations. PWY-7221: guanosine ribonucleotides de novo biosynthesis. PWY-4242: pantothenate and coenzyme A biosynthesis. PWY-7219: adenosine ribonucleotides de novo biosynthesis. PWY-6700: queuosine biosynthesis. PWY-5659: GDP-mannose biosynthesis. Glycolysis-1: glycolysis (from glucose 6-phosphate). PWY-7228: superpathway of guanosine nucleotides de novo biosynthesis. PEPTIDOGLYCANSYN-PWY: peptidoglycan biosynthesis. DTDPRHAMSYN-PWY: dTDP-L-rhamnose biosynthesis. PWY-5484: glycolysis II (from fructose 6-phosphate). PWY-6609: adenine and adenosine salvage. PWY-6386: UDP-N-acetylmuramoyl-pentapeptide biosynthesis. PWY-6277: superpathway of 5-aminoimidazole ribonucleotide biosynthesis. ARGSYNBSUB-PWY: L-arginine biosynthesis. PWY-6385: peptidoglycan biosynthesis. PWY-6122: 5-aminoimidazole ribonucleotide biosynthesis. PWY-5030: L-histidine degradation. PWY-7282: 4-amino-2-methyl-5-phosphomethylpyrimidine biosynthesis. CALVIN-PWY: Calvin–Benson–Bassham cycle. PWY-7456: mannan degradation. PWY-6936: seleno-amino acid biosynthesis. PWY-6703: preQ0 biosynthesis. COA-PWY: coenzyme A biosynthesis. NONOXIPENT-PWY: pentose phosphate pathway. PWY-7199: pyrimidine deoxyribonucleosides salvage. VALSYN-PWY: L-valine biosynthesis. P163-PWY: L-lysine fermentation to acetate and butanoate. PWY-6163: chorismate biosynthesis from 3-dehydroquinate. FASYN-INITIAL-PWY: superpathway of fatty acid biosynthesis initiation. The following codes include multiple metabolic pathways for different microorganisms: Calvin-PWY (Bacteroides caccae and B. uniformis), Glycolysis-1 (B. uniformis, B. vulgatus and B. caccae), PWY-3841 (B. uniformis and B. vulgatus), PWY-4242 (B. uniformis and B. vulgatus), PWY-5484 (B. uniformis and B. vulgatus), PWY-6277 (B. uniformis and B. vulgatus), PWY-6609 (B. vulgatus and B. caccae), PWY-7199 (B. uniformis and B. vulgatus), PWY-7219 (B. uniformis and Anaerostipes hadrus), PWY-7221 (B. uniformis and A. hadrus). (D) Hierarchical all-against-all association testing (HAllA) describing the effect of taxonomic clades and metabolic pathways more abundant after FMD on several clinical parameters, considering pairwise Pearson correlation coefficients adjusted by false discovery rate (FDR < 0.25). Red and blue cells indicate positive and negative correlations, respectively. Colour intensity is in proportion to magnitude.
Figure 4
Figure 4
(A) Clustering of metagenomic samples of metabolic pathway abundances using. Bray–Curtis dissimilarity method was used to determine which participants were grouped. Several samples from the same participant corresponding to Western-Type Diet (WD) and Fibre-Enriched Mediterranean-Type Diet (FMD) interventions were discriminated from the rest of the individuals, highlighting a robust microbiota was not significantly affected by dietary interventions. (B) Differential profiles for robust and non-robust microbiotas through multi-omic data integration of metabolic profiles and metabolic pathways determined by shotgun sequencing using the DIABLO biomarker discovery pipeline. (C) Variable importance coefficients obtained in DIABLO pipeline for metabolites and metabolic pathways in robust and non-robust microbiotas. TMAO: Trimethylamine N-oxide. HISTSYN-PWY: L-histidine biosynthesis. HISDEG-PWY: L-histidine degradation. PWY-5667: CDP-diacylglycerol biosynthesis. P163-PWY: L-lysine fermentation to acetate and butanoate. NONOXIPENT-PWY: pentose phosphate pathway. PWY-6700: queuosine biosynthesis. PWY-7219: adenosine ribonucleotides de novo biosynthesis. PWY-5030: L-histidine degradation. PWY-6121: 5-aminoimidazole ribonucleotide biosynthesis. DTDPRHAMSYN-PWY: dTDP-L-rhamnose biosynthesis. RHAMCAT-PWY: L-rhamnose degradation. PANTO-PWY: phosphopantothenate biosynthesis. PWY-7357: thiamin formation from pyrithiamine and oxythiamine. PWY66–400: glycolysis VI. COA-PWY: coenzyme A biosynthesis. PWY-7221: guanosine ribonucleotides de novo biosynthesis. Glycolysis-1: glycolysis (from glucose 6-phosphate). PWY-6897: thiamin salvage. PWY-5484: glycolysis (from fructose 6-phosphate). PWY 6277: superpathway of 5-aminoimidazole ribonucleotide biosynthesis. PWY-7111: pyruvate fermentation to isobutanol. PWY-7323: superpathway of GDP-mannose-derived O-antigen building blocks biosynthesis. PWY-1042: glycolysis. PANTOSYN-PWY: pantothenate and coenzyme A biosynthesis. CALVIN-PWY: Calvin–Benson–Bassham cycle. PWY-5103: L-isoleucine biosynthesis. PWY0-1586: peptidoglycan maturation. PWY-5659: GDP-mannose biosynthesis. 1CMET2-PWY: N10-formyl-tetrahydrofolate biosynthesis. NAGLIPASYN-PWY: lipid IVA biosynthesis. PWY-6122: 5-aminoimidazole ribonucleotide biosynthesis. ANAGLYCOLYSIS-PWY: glycolysis (from glucose). PWY-6125: superpathway of guanosine nucleotides de novo biosynthesis. PWY-7222: guanosine deoxyribonucleotides de novo biosynthesis. PWY-7199: pyrimidine deoxyribonucleosides salvage. The following codes include multiple metabolic pathways for different microorganisms: CALVIN-PWY (Bacteroides caccae and B. uniformis), RHAMCAT-PWY (B. vulgatus and B. caccae), PWY-1042 (B. uniformis and B. vulgatus), PWY-7357 (B. uniformis and B. caccae), PWY-7111 (B. uniformis, B. vulgatus and B. caccae). Hierarchical all-against-all association testing (HAllA) describing the effect of microbial gene families from a robust (D) and non-robust (E) microbiota on several clinical parameters, considering pairwise Pearson correlation coefficients adjusted by false discovery rate (FDR < 0.25). Red and blue cells indicate positive and negative correlations, respectively. Colour intensity is in proportion to magnitude.
Figure 4
Figure 4
(A) Clustering of metagenomic samples of metabolic pathway abundances using. Bray–Curtis dissimilarity method was used to determine which participants were grouped. Several samples from the same participant corresponding to Western-Type Diet (WD) and Fibre-Enriched Mediterranean-Type Diet (FMD) interventions were discriminated from the rest of the individuals, highlighting a robust microbiota was not significantly affected by dietary interventions. (B) Differential profiles for robust and non-robust microbiotas through multi-omic data integration of metabolic profiles and metabolic pathways determined by shotgun sequencing using the DIABLO biomarker discovery pipeline. (C) Variable importance coefficients obtained in DIABLO pipeline for metabolites and metabolic pathways in robust and non-robust microbiotas. TMAO: Trimethylamine N-oxide. HISTSYN-PWY: L-histidine biosynthesis. HISDEG-PWY: L-histidine degradation. PWY-5667: CDP-diacylglycerol biosynthesis. P163-PWY: L-lysine fermentation to acetate and butanoate. NONOXIPENT-PWY: pentose phosphate pathway. PWY-6700: queuosine biosynthesis. PWY-7219: adenosine ribonucleotides de novo biosynthesis. PWY-5030: L-histidine degradation. PWY-6121: 5-aminoimidazole ribonucleotide biosynthesis. DTDPRHAMSYN-PWY: dTDP-L-rhamnose biosynthesis. RHAMCAT-PWY: L-rhamnose degradation. PANTO-PWY: phosphopantothenate biosynthesis. PWY-7357: thiamin formation from pyrithiamine and oxythiamine. PWY66–400: glycolysis VI. COA-PWY: coenzyme A biosynthesis. PWY-7221: guanosine ribonucleotides de novo biosynthesis. Glycolysis-1: glycolysis (from glucose 6-phosphate). PWY-6897: thiamin salvage. PWY-5484: glycolysis (from fructose 6-phosphate). PWY 6277: superpathway of 5-aminoimidazole ribonucleotide biosynthesis. PWY-7111: pyruvate fermentation to isobutanol. PWY-7323: superpathway of GDP-mannose-derived O-antigen building blocks biosynthesis. PWY-1042: glycolysis. PANTOSYN-PWY: pantothenate and coenzyme A biosynthesis. CALVIN-PWY: Calvin–Benson–Bassham cycle. PWY-5103: L-isoleucine biosynthesis. PWY0-1586: peptidoglycan maturation. PWY-5659: GDP-mannose biosynthesis. 1CMET2-PWY: N10-formyl-tetrahydrofolate biosynthesis. NAGLIPASYN-PWY: lipid IVA biosynthesis. PWY-6122: 5-aminoimidazole ribonucleotide biosynthesis. ANAGLYCOLYSIS-PWY: glycolysis (from glucose). PWY-6125: superpathway of guanosine nucleotides de novo biosynthesis. PWY-7222: guanosine deoxyribonucleotides de novo biosynthesis. PWY-7199: pyrimidine deoxyribonucleosides salvage. The following codes include multiple metabolic pathways for different microorganisms: CALVIN-PWY (Bacteroides caccae and B. uniformis), RHAMCAT-PWY (B. vulgatus and B. caccae), PWY-1042 (B. uniformis and B. vulgatus), PWY-7357 (B. uniformis and B. caccae), PWY-7111 (B. uniformis, B. vulgatus and B. caccae). Hierarchical all-against-all association testing (HAllA) describing the effect of microbial gene families from a robust (D) and non-robust (E) microbiota on several clinical parameters, considering pairwise Pearson correlation coefficients adjusted by false discovery rate (FDR < 0.25). Red and blue cells indicate positive and negative correlations, respectively. Colour intensity is in proportion to magnitude.
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