Table 3.
Randomized clinical trials examining effects of diet macronutrient or energy manipulation on human gut microbiota composition and metabolites.
| Reference | Design1 | Microbiota method | Results- Microbiota | Results- Microbiota metabolites |
|---|---|---|---|---|
| Carbohydrate and fat manipulation | ||||
| Duncan et al., 2007 | n = 18 obese M, 4 weeks, CO; hypocaloric high PRO diets: highPRO + modCHO (35/30/35, 12g NSP), and highPRO + lowCHO (4/30/66, 6 g NSP) | Targeted; FISH | lowCHO vs modCHO: ↓Roseburia–E. rectale group; ↔Total bacteria, Bacteroides–Prevotella, F. prausnitzii, Bifidobacterium, Clostridial clusters XIVa, XIVb, IX, R. bromii, R. flavefaciens, Lactobacillus-Enterococcus | lowCHO vs. modCHO: ↓Fecal butyrate; ↔fecal acetate, propionate, BCFA, NH3 |
| Both diets: ↓Total bacteria, Bifidobacterium, Roseburia–E. rectale group | Both diets: ↓Fecal acetate, propionate, butyrate, isovalerate, valerate, NH3 | |||
| Duncan et al., 2008 | n = 23 obese M, 4 weeks, CO; hypocaloric high PRO diets: highPRO + modCHO (35/30/35, 12 g NSP), and highPRO + lowCHO (4/30/66, 6 g NSP) | Targeted; FISH | lowCHO vs. modCHO: ↓Roseburia–E. rectale group; ↔Bacteroides, Firmicutes, Bifidobacterium, Clostridium coccoides | NA |
| Both diets: ↓total bacteria, Bifidobacterium, Roseburia–E. rectale group; ↑C. coccoides | ||||
| Russell et al., 2011 | n = 17 obese M, 4 weeks, CO; hypocaloric high PRO diets: highPRO + modCHO (35/28/37, 13 g NSP), and highPRO + lowCHO (5/29/66, 9 g NSP) | Targeted; FISH | lowCHO vs. modCHO: ↓Roseburia–E. rectale group; ↔Bacteroides, Lachnospiraceae, F. prausnitzii | lowCHO vs. modCHO: ↓Fecal acetate, butyrate, total SCFA, plant-derived phenolics, fatty acid-derived bacterial metabolites; ↑Fecal pH, N-nitroso compounds |
| Both diets: ↓total bacteria | Both diets: ↑Fecal isovalerate, valerate, N-nitroso compounds; ↓fecal propionate | |||
| Carbohydrate and protein manipulation | ||||
| Beaumont et al., 2017 | n = 38 (13M) ovwt, 3 weeks, PA; PRO and CHO supplementation: casein (35/34/29, 25 g fiber), soy PRO (37/32/29, 22 g fiber), or CHO (54/14/29, 20 g fiber) | 16S rRNA gene sequencing | No effects of diet on fecal or rectal mucosa microbiota | Fecal metabolome: ↓butyrate and ↑AA-derived bacterial metabolites (e.g., BCFA) which differed by PRO group |
| Urine metabolome: ↑AA-derived bacterial metabolites (e.g., BCFA) which differed by PRO group | ||||
| Plasma metabolome: No differences between groups in bacterially derived metabolites | ||||
| Carbohydrate, protein and fat manipulation | ||||
| Ley et al., 2006 | n = 12 obese adults, 1 year, PA; hypocaloric diets: modFat (30% kcal fat) or lowCHO (25% kcal CHO) | 16S rRNA gene sequencing | No differences between groups | NA |
| Both groups: ↑Bacteroidetes; ↓Firmicutes | ||||
| Brinkworth et al., 2009 | n = 91 (36M) ovwt/obese, 8 weeks, PA; lowCHO + highFAT (5/35/60, 13 g fiber) or highCHO + lowFAT (46/24/30, 32 g fiber) | Targeted; culture | lowCHO vs. high CHO: ↓Total anaerobes, Bifidobacterium; ↔Total anaerobes, coliforms, Escherichia coli, Lactobacillus | lowCHO vs. high CHO: ↓Fecal acetate, butyrate, total SCFA; ↔fecal pH and NH3, urinary phenols and p-cresol |
| Wu et al., 2011 | n = 10 (6M) healthy adults, 10 days, PA: highFiber + lowFAT (69/18/13, 52 g fiber); lowFiber + highFAT (35/27/38, 22 g fiber) | 16S rRNA gene sequencing; SM | Shifts in composition within 24 h, but no differences between diets. | NA |
| Windey et al., 2012 | n = 20 (6M) adults, 2 weeks, CO: lowPRO (60/12/17, 17 g fiber); highPRO (41/27/32, 15 g fiber) | DGGE | No differences | highPRO vs lowPRO: ↑Urinary p-cresol, fecal isobutyric and isovaleric acids; ↔fecal p-cresol, acetate, propionate, butyrate |
| Fava et al., 2013 | n = 88 (43M) adults at risk for MetS, 24 weeks, PA: highSFA + highGI (43/15/38) highSFA + highGI (43/15/38) highMUFA + highGI (43/16/38) highMUFA + lowGI (46/17/35) highCHO + highGI (51/20/27) highCHO + lowGI (55/18/23) All diets 17–22 g NSP | Targeted; FISH | highMUFA: ↓Total bacteria | ↔Acetate, butyrate, propionate, valerate, caproate |
| highCHO + highGI: ↑Bifidobacterium vs. highSFA + highGI; ↑Bacteroides vs. baseline | ||||
| highCHO: ↑Bifidobacterium vs. baseline | ||||
| highCHO + lowGI: ↑F. prausnitzii vs. baseline | ||||
| David et al., 2014 | n = 10 (6M) adults, 5 days, CO; Plant-based diet (68/10/22, 26 g fiber/1000 kcal), and Animal-based diet (0/30/70, 0 g fiber) | 16S rRNA gene sequencing | Animal diet: Transient change in diversity, changes in 22 bacterial clusters, ↑bile acid tolerant and putrefactive taxa (e.g., B. wadsworthia, Alistipes putredinis, Bacteroides), Akkermansia, R. gnavus, Escherichia; ↓Roseburia, E. rectale, R. bromii | Animal vs plant-metabolites: ↓Fecal acetate, butyrate; ↑fecal isovalerate, isobutyrate, deoxycholic acid (secondary bile acid) |
| Plant diet: Changes in 3 clusters, ↓B. wadsworthia, Clostridium, Ruminococcus | Animal vs. plant-gene expression: ↑bile salt hydrolases, sulfite reductases, AA catabolism; ↓AA biosynthesis | |||
| Energy balance manipulation | ||||
| Jumpertz et al., 2011 | n = 21M (lean or obese), 3 days, CO; energy manipulation: 2400 kcal/day (60/24/16), and 3400 kcal/day (60/24/16); diets were fiber-matched | 16S rRNA gene sequencing | Overeating: ↓Bacteroidales; ↑Clostridia Undereating: ↑Bacteroidales; ↓Clostridia | NA |
AA, amino acid; BCFA, branched-chain fatty acid; CHO, carbohydrate; CO, crossover study; DGGE, differential gradient gel electrophoresis; FISH, fluorescence in-situ hybridization; GI, glycemic index; MetS, metabolic syndrome; MUFA, monounsaturated fatty acid; NSP, non-starch polysaccharides; ovwt; overweight; PA, parallel-arm randomized trial; PRO, protein; SCFA, short-chain fatty acid; SFA, saturated fatty acid; SM, shotgun metagenomics; ↑, increase/higher; ↓, decrease/lower; ↔, no change/no difference. Genus abbreviations: B., Bilophila; C., Clostridium; E., Eubacterium; F; Faecalibacterium; R, Ruminococcus. 1Macronutrient proportions are percent total energy from CHO/PRO/FAT.