Ketogenic Diet and Microbiota: Friends or Enemies?
Abstract
:1. Introduction
1.1. The Human Gut Microbiota and the Microbiome
1.2. Bioactive Products
1.3. Interindividual Variability of Microbiota
1.4. Very Low Carbohydrate Ketogenic Diet (VLCKD)
1.5. Physiology of Ketosis
2. Methods
3. Results
How VLCKD Affects the Gut Microbiome
4. Discussion
4.1. Friend or Enemies?
4.2. Factors Affecting Microbiota during a VLCKD: What Should We Consider?
4.2.1. Fats
4.2.2. Sweeteners
4.2.3. Pre and Probiotics
4.2.4. Proteins
5. Conclusions, Perspective and Future Research
- Introduce the use of whey and plant proteins (i.e., pea protein);
- Reduce the intake of animal protein;
- Implement fermented food and beverages (yoghurt, water and milk kefir, kimchi, fermented vegetables);
- Introduce properly prebiotics and specific probiotics (if needed);
- Reduce omega 3 to omega 6 fatty acids ratio (increase omega 3 while decreasing omega 6);
- Introduce an accurate quantity and quality of unsaturated fatty acids;
- Avoid artificial sweeteners (stevia?) and processed foods;
- Test your microbiome if needed (analysis of 16S rRNA to identify biodiversity and richness).
Author Contributions
Funding
Conflicts of Interest
References
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Subjects | Subjects Characteristics | Duration | Type of KD | Measured KBs (Y/N) | KBs’ Level | Genome Analysis Technique | Main Findings of Bacteria Changes | |
---|---|---|---|---|---|---|---|---|
Tagliabue et al. (2017) [50] | 6 patients (3 females 3 males) pre-post | Glucose Transporter 1 Deficiency Syndrome | 3 months | First 1:1 ratio with gradual increase of 2:1, 3:1 and or 4:1 KD ratio | Ketonuria | Not mentioned | DNA extraction RT-qPCR analysis | INCREASE Desulfovibrio spp. |
Swidsinki et al. (2017) [52] | 25 MS patients and 14 controls | Auto Immune Multiple Sclerosis | 6 months | >50 g carbohydrate, >160 g fat, <100 g protein | Ketonemia and ketonuria | β-hydroxybutyric acid ≥ 500 μmol/L; acetoacetate ≥ 500 μmol/L | FISH with ribosomial RNA derived probes | DECREASE β-diversity, DECREASE substantial bacteria groups after two weeks, after six months completely recover the concentration to baseline |
Newell et al. (2017) [67] | 25 juvenile male C57BL/6 (B6) and 21 BTBR mice | Autism Spectrum Disorder | 10–14 days | 75% kcal fat | Ketonemia | β-hydroxybutyric acid 5.1 ± 0.8 mmol/L | DNA extraction RT-qPCR analysis | DECREASE in total bacterial content both in cecal and fecal analysis, DECREASE A. muciniphila both in cecal and fecal matter, INCREASE Enterobacteriaceae in fecal matter |
Burke et al. (2019) [47] | 10 LCHF, 10 PCHO, 9 HCHO pre-post | Elite race walkers | 3 weeks | 78% fat, 2.2 g/kg BM/day protein, <50 g carbohydrate | Ketonemia | β-hydroxybutyric acid ≥ 1.0 mmol/L | 16S rRNA-gene amplicon sequencing | INCREASE in Bacteroides and Dorea spp. DECREASE in Faecalibacterium spp. |
Lindefeldt et al. (2019) [70] | 12 children (parents as controls) pre-post | Therapy-resistant epilepsy | 3 months | 4:1 in 7 children, 3.5:1 in 2, and 3:1 in 3 KD ratio | Ketonemia | β-hydroxybutyric acid 0.3 ± 0.2 mmol/L | Shotgun metagenomic DNA sequencing | DECREASE in abundance of bifidobacterium, E. rectale, E. dialister, INCREASE in E. coli, changes in 29 SEED subsystem: reduction of seven pathways of carbohydrate metabolism |
Olson et al. (2018) [53] | Juvenile SPF wild-type Swiss Webster mice, GF wild type SW mice, SPF C3HeB/FeJ KCNA1 KO mice | 6 Hz induced seizure model of refractory epilepsy | 3 weeks | 6:1 KD ratio | Ketonemia (liver, colon, intestine) and normalized to SPF (specific-pathogen free) | β-hydroxybutyric acid (different levels accepted) | 16S rRNA-gene amplicon sequencing | DECREASE in α diversity, INCREASE A. muciniphila, Parabacteroides, Suttarella and Erysipelotrichaceae |
Zhang et al. (2018) [69] | 20 patients (14 males 6 females) pre-post | Refractory epilepsy | 6 months | 4:1 KD ratio (plant fat 70%, 1 g/kg BM/day from animal source | Ketonemia | β-hydroxybutyric acid 2.85 ± 0.246 and 3.01 ± 0.238 mmol/L (effective and ineffective group) | 16S rRNA-gene amplicon sequencing | DECREASE in α diversity, Firmicutes, Actinobacteria, INCREASE in Bacteroidetes |
Ma et al. (2017) [51] | C57BL/6 male mice | Healthy mice | 4 months | 75% fat (saturated, monounsaturated, polyunsaturated), 8.6% protein, 3.2% carbohydrates | Ketonemia | β-hydroxybutyric acid around 1.5 mmol/L | 16S rRNA-gene amplicon sequencing | DECREASE in diversity, INCREASE A. muciniphila, Lactobacillus, DECREASE Desulfovibrio, Turicinabacter |
Xie et al. (2017) [68] | 14 patients and 30 healthy infants | Refractory epilepsy | 1 week | lipid-to-non-lipid ratio of 4:1 (40% medium chain, 60% long chain), 60–80 kcal/kg per day, 1–1.5 g/kg protein | Not mentioned | Not mentioned | 16S rRNA-gene amplicon sequencing | DECREASE Proteobacteria (Cronobacter), INCREASE Bacteroidetes (Bacteroides, Prevotella), Bifidobacterium |
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Paoli, A.; Mancin, L.; Bianco, A.; Thomas, E.; Mota, J.F.; Piccini, F. Ketogenic Diet and Microbiota: Friends or Enemies? Genes 2019, 10, 534. https://doi.org/10.3390/genes10070534
Paoli A, Mancin L, Bianco A, Thomas E, Mota JF, Piccini F. Ketogenic Diet and Microbiota: Friends or Enemies? Genes. 2019; 10(7):534. https://doi.org/10.3390/genes10070534
Chicago/Turabian StylePaoli, Antonio, Laura Mancin, Antonino Bianco, Ewan Thomas, João Felipe Mota, and Fabio Piccini. 2019. "Ketogenic Diet and Microbiota: Friends or Enemies?" Genes 10, no. 7: 534. https://doi.org/10.3390/genes10070534