Reciprocal interactions between gut microbiota and autophagy

Table 1 Data supporting the existence of a systemic regulation of autophagy by the gut microbiota

Ref.		Impact on autophagy
		Brain	Liver	Muscles
[49,74-76]	Diet-induced changes in the gut microbiota	Feeding of mother mice with an HSHF diet: Changes in the expression levels of LC3A-I/LC3A-II/ LC3B-I/LC3B-II in the offspring.	Feeding mice or rats with an HF diet: Changes in the expression levels of LC3, p62, mTOR, and p-AKT and modulation of the LC3-II amount.
[55,56,59,70]	Mice with specific gut microbiota	AD mice1: Modulation of the lysosomal activity (Cathepsin L) and SIRT1 activity and changes in the expression levels of Beclin-1, p62, and SIRT1.	ASF colonized mice: Changes in the expression of a set of genes related to autophagy/membrane trafficking (Uvrag, Atg14, Becn1, Bcl2l1, and Pik3c3) and lysosomal functions (Chmp4c and Chmp2a) compared to germ-free mice.
		FMT from patients with AIS to mice: Changes in the expression levels of Becn1, ATG12, and LC3 expression and in the amount of LC3-II.
[71,79]	Germ free or antibiotic-treated animals		Antibiotic treatment of mice fed a normal diet: Alteration of the basal expression of LC3 compared to controls.	Germ free piglets: Changes in the expression levels of LC3A, LC3B, and Becn1 and of mTOR, p-mTOR, AKT, and p-AKT levels compared to normal and/or FMT piglets.
[55,56,75,76,78]	Probiotics	SLAB512: Modulation of SIRT1 activity and changes in the expression levels of Beclin-1, p62, and SIRT-1 as well as in the LC3-II amount in AD mice1.	Limosilactobacillus reuteri: Modulation of the expression levels of mTOR and p-AKT in HFD-fed rats.	Lacticaseibacillus rhamnosus, Pediococcus acidilactici, Bifidobacterium adolescentis: Changes in the expression levels of LC3 and ATG7 in rats fed a high-calorie diet.
[52,71,74,77,80]	Gut microbiota-derived products	UA: Modulation of LC3-II/LC3-I and p-mTOR/mTOR ratio and changes in the expression levels of ATG7 and p62 in mouse models of aging3.	SCFAs: Activation of the PPARγ-UCP2-AMPK pathway, and induction of autophagy flux and lysosomal activity in mouse hepatocyte AML-12 cells.	UA: Induction of mitophagy in Caenorhabditis elegans and in rodents.
			FXR and TGR54: Involved in autophagy modulation.	UB: Modulation of LC3-II/LC3-I, p-mTOR/mTOR and p-ULK1/ULK1 ratio and change in the expression level of p62 in a rat model of ischemia/reperfusion injury.

¹AD mice: Mouse model of Alzheimer’s disease (3xTg-AD mice).

²SLAB51: A combination of nine probiotic strains (Streptococcus thermophilus, Bifidobacterium longum, B. breve, B. infantis, Lactobacillus acidophilus, Lactiplantibacillus plantarum, Lacticaseibacillus paracasei, Lactobacillus delbrueckii subsp. bulgaricus, and Levilactobacillus brevis).

³D-gal-treated mice and 12-mo-old mice.

⁴FXR and TGR5: Bile acid receptors.

HSHF diet: High sugar and high fat diet; HF diet: High fat diet; FMT: Fecal microbiota transplantation; SCFAs: Short chain fatty acids (propionate and butyrate); AIS: Acute ischemic stroke; ASF: Altered Schaedler’s flora; UA: Urolithin A; UB: urolithin B.