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Ketogenic Diet and Microbiota: Friends or Enemies?


Ketogenic Diet and Microbiota: Friends or Enemies?

Antonio Paoli et al. Genes (Basel).


Over the last years, a growing body of evidence suggests that gut microbial communities play a fundamental role in many aspects of human health and diseases. The gut microbiota is a very dynamic entity influenced by environment and nutritional behaviors. Considering the influence of such a microbial community on human health and its multiple mechanisms of action as the production of bioactive compounds, pathogens protection, energy homeostasis, nutrients metabolism and regulation of immunity, establishing the influences of different nutritional approach is of pivotal importance. The very low carbohydrate ketogenic diet is a very popular dietary approach used for different aims: from weight loss to neurological diseases. The aim of this review is to dissect the complex interactions between ketogenic diet and gut microbiota and how this large network may influence human health.

Keywords: gut microbiome; gut microbiota; intestinal microbiome; ketogenic diet; ketogenic diet and fat.

Conflict of interest statement

The authors declare no conflict of interest.


Figure 1
Figure 1
The influence of a very low carbohydrate ketogenic diet and ketone bodies in gut health. BHB: β-hydroxybutyrate, AcAc: Acetoacetate.
Figure 2
Figure 2
Effects of ketogenic diet on different tissues and the microbiome. KD has a contradictory role on hunger but the net effect is anorexigenic. KD Exerts orexigenic effects: The increase of brain GABA (γ-aminobutyric acid) through BHB (β-hydroxybutyric acid); the increase of AMP (adenosine monophosphate -activated protein) phosphorylation via BHB; the increase of circulating level of adiponectin; the decreases of ROS (reactive oxygen species). KD Exerts anorexigenic effect: the increase of circulating post meal FFA (free fatty acids); a maintained meal’s response of CCK (cholecystokinin); a decrease of circulating ghrelin; a decrease of AMP phosphorylation; a decrease of AgRP (agouti-related protein) expression. KD has positive effects on Alzheimer’s disease through: an increase levels of CBF (cerebral blood flow) in VMH (ventromedial hypothalamus); a decrease expression of mTOR (mammalian target of rapamycin) by the increase of the level of eNOS (endothelial nitric oxide synthase) protein expression; an increased expression of P-gp (P-glycoprotein), which transport Aβ (amyloid-β) plaques; an improvement of BBB’s (blood–brain-barrier) integrity. KD has beneficial effects on epileptic seizure by the modulation of hippocampal GABA/glutamate ratio. It exerts anti-seizure effects through: An increase level of GABA, an increase content of GABA: glutamate ratio. KD plays a main role on fat loss. It exerts positive effects on adipose tissue through: a decrease of liposynthesis, an increase of lipid oxidation and an increase in adiponectin. KD has a contradictory role on microbiome. KD generally exerts its effect through: a decrease in α diversity (the diversity in a single ecosystem/sample) and a decrease in richness (number of different species in a habitat/sample). KD influences the gut health through metabolites produced by different microbes: an increase/decrease in SCFA (short chain fatty acids), an increase in H2S (hydrogen sulfide) and a decrease in lactate. KD to microbiome to the brain: KD may influence the CNS (central nervous system) not only directly but also indirectly. The KD effects on the brain are supposed to be mediated by microbiota through an increase of SCFAs and a decrease of γ-glutamyl amino acid. A. muciniphila and Lactobacillus are known as SCFAs producers. SCFAs are transported by monocarboxylase transporters expressed at BBB. Desulfovibrio has the ability to produce hydrogen sulfide and, as a consequence, impair intestinal mucosal barrier. A reduction in Desulfovibrio and an enhancement in A. muciniphila and Lactobacillus may facilitate BBB and neurovascular amelioration. KD to microbiome to the adipose tissue: KD may indirectly influence the adipose tissue by the microbiota through a decrease in glycemia via adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, an increase in insulin sensitivity and an increase in SCFAs. The great amount of A. muciniphila and Lactobacillus spp. led to the reduction of body weight and glycemia. It has been demonstrated that patient with type 2 diabetes, treated with metformin, revealed higher level of A. muciniphila, may be to the ability of metformin on decreasing body weight by the activation of AMPK pathways (amp-activated protein kinase). A. muciniphila is related with the enhancement of insulin sensitivity and Lactobacillus may be playing the same effects through SFCAs production: Several studies showed that Lactobacillus is strictly connected with body weight loss.

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