TABLE 3.

Potential treatments targeting microbiota in the gut–kidney-heart axis.

Potential treatments	Key findings	References
Diet intervention	Dietary intervention: The first-line treatment for CKD.	Lobel et al. (2020)
	Plant-dominant low-protein diet: Alter gut microbiome, modulate uremic toxin generation, delay CKD progression and reduce cardiovascular risks.	Conlon and Bird (2014), Gluba-Brzózka et al. (2017), Kalantar-Zadeh et al. (2020)
	High-fiber diet: Restore gut microbiome, reduce renal fibrosis, cardiac fibrosis, and left ventricular hypertrophy via inhibiting Egr1.	Kieffer et al. (2016), Marques et al. (2017)
	High sulfur amino acid-containing diet: Modulate the indole and IS levels by sulfide inhibition of TnaA, ameliorate kidney function in CKD mice.	Lobel et al. (2020)
	Low phosphate diet: Alleviate mitochondrial injury, vascular calcification, cardiac hypertrophy and failure.	Liu et al. (2018)
	Ketogenic diet: Protect obesity-associated CVD, improve renal function, increase beneficial gut microbiota; might aggravate renal dysfunction.	Ma et al. (2018), Olson et al. (2018), Bruci et al. (2020), Dowis and Banga (2021), Jia et al. (2021), Zhang (2021), Rojas-Morales et al. (2022)
Probiotics	Lactobacillus acidophilus ATCC 4356: Regulate oxidative stress and inflammation, and reduce atherosclerosis.	Chen et al. (2013)
	Lactobacillus acidophilus : Reduce serum dimethylamine and nitrosodimethylamine, and improve ESRD.	Yoshifuji et al. (2016)
	Lebenin: Inhibit uremic toxins, restore microbiota of uremic patients.	Sabatino et al. (2015)
	L. casei Zhang: Ameliorate AKI and CKD progression by increasing the levels of SCFAs and niacinamide.	Zhu et al. (2021)
	Bifidobacterium: inhibit inflammation, protect intestinal barrier, and alleviate CKD progression.	Rui-Zhi et al. (2020)
	Streptococcus thermophilus, Lactobacillus acidophilus and Bifidobacterium longum : Reduce BUN levels, improve kidney function in CKD patients.	Ranganathan et al. (2009), Ranganathan et al. (2010)
Prebiotics	p-inulin: Reduce inflammation, serum PCS and IS, improve metabolic function.	Cani et al. (2007), Meijers et al. (2010)
	Acarbose: Reduce serum p-cresol concentration.	Evenepoel et al. (2006)
	Fiber: Reduce inflammation and mortality in CKD patients.	Krishnamurthy et al. (2012)
	Resistant starch: Ameliorate IS, PCS and CKD in rats.	Kieffer et al. (2016)
Genetically engineered bacteria	S-sulfhydration or mutation of E. coli TnaA reduces its activity, thus alleviating serum IS levels and kidney injury.	Lobel et al. (2020)
	Deleting Bacteroides TnaA eliminates the production of indole and controls IS levels.	Devlin et al. (2016)
Fecal microbiota transplantation	FMT from CKD patients: Induce serum uremic toxins, renal fibrosis and oxidative stress in mice.	Barba et al. (2020)
	FMT from AKI mice: Aggravate the kidney injury in I/R-induced AKI mice.	Zhu et al. (2021)
	FMT from healthy mice: Improve gut microbiota disturbance and decrease PCS accumulation in CKD mice.	Caggiano et al. (2020)
Bacterial metabolite modulation	Indole absorbents: AST-120. Decrease serum IS and AGEs, delay the initiation of hemodialysis, restore intestinal barrier and reduce inflammation in CKD models.	Ueda et al. (2006), Ueda et al. (2007), Yamaguchi et al. (2017), Huang et al. (2020b)
	TMA inhibitor: DMB. Inhibit microbial TMA formation, plasma TMAO levels, endogenous macrophage foam cell formation and atherosclerotic lesion development.	Wang et al. (2015)
	AGE formation inhibitors (synthetic compounds and natural products): Block sugar attachment to proteins, attenuate glycoxidation, break down formed AGE crosslinks	Liu M. et al. (2020)
	RAGE antibody or gene knockout: Alleviate renal injury and development of nephropathy.	Flyvbjerg et al. (2004)
	Small molecule inhibitors of RAGE (RAGE229): Reduce diabetic complications by inhibiting the interaction between the cytoplasmic tail of RAGE and Diaphanous-1.	Manigrasso et al. (2021)
Antibiotics	Vancomycin: Decreased IS and PCS in ESRD patients.	Nazzal et al. (2017)
	Antibiotics: Improve kidney injury by preventing inflammatory response.	Furusawa et al. (2013)
	IR-induce AKI and CKD models in germ-free mice show more severe renal damage.	Jang et al. (2009), Mishima et al. (2017)
Conventional drugs	Lubiprostone: Ameliorate CKD progression and uremic toxins, restore Lactobacillaceae family and Prevotella genus.	Mishima et al. (2015)
	Metformin: Increase Lactobacillus and Akkermansia, improve atherosclerosis and gut barrier integrity.	Lee and Ko (2014), Li et al. (2016), de La Cuesta-Zuluaga et al. (2017), Caggiano et al. (2020)
	Acarbose: Increase Lactobacillus and Bifidobacterium, deplete Bacteroides, regulate bile acid metabolism	Gu et al. (2017)
	SGLT2i: Reduce uremic toxins, modulate Firmicutes to Bacteroidetes ratio, increase SCFA-forming bacteria.	Lee et al. (2018), Mishima et al. (2018), Caggiano et al. (2020)
Traditional Chinese medicine	Jian-Pi-Yi-Shen decoction: Improve renal function via modulating Clostridium_XIVb in CKD rats.	Zheng et al. (2020)
	Qing-Re-Xiao-Zheng formula: Protecte renal function via regulating gut microbiota dysbiosis and inhibiting inflammation in DKD rats.	Gao et al. (2021)
	Shenyan Kangfu tablet: Increase Firmicutes and decrease Bacteroidetes in diabetic mice.	Chen et al. (2021)
	Mahuang decoction: Ameliorate kidney impairment, restore microbiota dysbiosis.	Ming et al. (2021)