Table 3.
Effects of metabolic disorders, diet and gut microbiota on amyotrophic lateral sclerosis (ALS).
| Harmful | Protective | |
|---|---|---|
| Metabolism | ||
| Obesity | Decrease risk and progression Counteracts ALS hypermetabolism |
|
| Diabetes | Mixed effects (depends on ethnicity) IGT observed in patients Different mechanisms form classic diabetes |
|
| Dyslipidaemia | Increased risk of disease | Decreased mortality Early switch to lipid metabolism in motor neurons and muscles may be an early compensatory mechanism |
| MAFLD | Hepatic steatosis frequent finding Unknown significance |
|
| Diet | ||
| Fat intake | ω-3 PUFAs may exert a double-edge role | Associated with longer survival |
| Antioxidants | Lowers disease risk Intake correlates with higher functional scores Co-supply with ω-3 PUFAs may show synergic effects |
|
| Dietary patterns | Human: MeD Mice: caloric restriction worsens disease severity |
|
| Microbiota | ||
| Composition | Opportunistic gram-negative bacteria | SCFA-producing bacteria |
| Mechanisms | Endotoxemia, IEB permeability, gut inflammation Deletion of C9orf72 exaggerates systemic immune response |
Nicotinamide and SCFAs levels |
| Gut-brain axis | TDP-43 deposition in the gut of animal models Gut-to-brain transport not assessed |
|
| Gut microbiota-based Therapy | Mice: SCFAs alleviate motor symptoms | |