Table 2.
Summary of in vivo studies based on the application of fecal transplantation in kidney disease.
| Author, Year, Ref | AIM | FMT Modality | Experimental Design for FMT Procedure | Main Findings | Microbiome Evaluation | Effect on Uremic Toxins |
|---|---|---|---|---|---|---|
| Uchiyama et al., 2020 [85] |
Explore the role of uremic dysbiosis in CKD-associated IR and sarcopenia. |
Donor: CKD mice treated with adenine diet (0.2%). Recipient: healthy germ-free mice. |
FMT was performed once in healthy germ-free mice from control mice or CKD mice. | Uremic flora induced sarcopenia, IR, and intestinal permeability in recipient mice. | Decrease in Bacilli, Lactobacillales, and Lactonifactor. Increase in Erysipelotrichi, Erysipelotrichales Allobaculum, Clostridium, and Alistipes. |
↑ IS ↑ PHS ↑ HA ↑ IL-6 |
| Li et al., 2020 [24] |
Explore the role of gut microbiota in diabetic nephropathy. |
Donors: DN mice (STZ-treated) grouped by severe or moderate proteinuria. Recipient: Antibiotic-treated mice. |
Study 1: mice were treated with antibiotics and then with FMT from severe/mild proteinuria group, daily, for 3 days. After, FMT mice were treated with STZ. Study 2: STZ was administered before FMT in antibiotic-treated mice. FMT was performed from severe/mild proteinuria group, daily, for 3 days. |
Alterations in gut microbiome modulated the kidney function of DN models. The author suggests that Allobaculum and Anaerosporobacter may worsen renal function, while Blautia may be a protective factor in DN. |
Firmicutes were more abundant in mice treated with fecal content of mild proteinuria. Allobaculum increased in the recipients transplanted with severe proteinuria flora. Blautia increased in mice that received the microbiome from the mild proteinuria mice. |
FMT from severe proteinuria mice: ↑ TMAO ↑ LPS ↓ SCFAS FMT from moderate proteinuria mice: ↓ TMAO ↓ LPS ↑ SCFAS |
| Wang et al., 2020 [14] |
Explore the relationships between gut flora and renal failure. |
Donor: ESRD patients or healthy donors. Recipient: CKD mice (adenine treated) and CKD rats (5/6 nephrectomy treated with antibiotics). |
CKD mice: 200 ul (0.1 g/mL) of pooled stool was gavaged for 3 days. CKD rats: 1 mL (0.1 g/mL) of pooled stool was gavaged daily for 3 weeks. |
FMT from ESRD patients increased uremic toxins levels and aggravated kidney injury. FMT from healthy donors lowered serum creatinine, urea, and several uremic toxins. |
E. lenta was found to increase the production of HA and PAG. Fusobacterium nucleatum increased the production of indole and phenol. |
Mice/rats receiving ESRD stool: ↑ IS ↑ pCS ↑ PAG ↑ PhS ice/rats receiving healthy donor stool: ↓ TGF-β1 |
| Yang et al., 2020 [27] |
Explore the link between kidney and gut microbiota during AKI. |
Donor: sham-operated mice or IRI mice models. Recipient: germ-free mice. |
FMT was performed via gastric gavage on day 0 and day 10. | After renal IRI, gut microbiota modulated inflammation and severity of kidney injury. | NA | ↓ TNF-α ↓ IFN-γ |
| Liu et al., 2022 [135] |
Explore the role of FMT on CKD. |
Donor: sham-operated rats. Recipients: 1/2 nephrectomy rats treated with an antibiotic cocktail. |
FMT was performed daily for 21 days. | FMT improved kidney function and oxidative stress. | FMT restored the proportion of Lactobacillus johnsonii and Lactobacillus intestinalis. | ↓ IS ↓ PCS ↓ PhS ↓ Phenylacetyl glycine ↓ TMAO |
| Barba et al., 2020 [136] |
Explore the role of FMT on the metabolic complication and uremic toxins level. |
Donor: healthy mice. Recipient: CKD mice induced with adenine diet (0.25%). |
FMT was performed once a week for a total of three weeks by oral gavage. | FMT improved glucose intolerance, and IR. | FMT induced a significant amelioration α-diversity and restored the abundance of Oscillospira and Desulfovibrio. | ↓ PCS ↓ PCG |
| Hu et al., 2020 [137] |
Investigate the role of microbiome on diabetic nephropathy. |
Donor: healthy rats. Recipient: DN rats (STZ-treated rat). |
FMT was performed once a day for 3 days. | FMT improved tubulointerstitial injury and inflammation and reduced both triglycerides and serum acetate levels. |
FMT restored the proportion of Prevotellaceae, Ruminococcaceae, and Lactobacillaceae. | ↓ IL-6 |
| Lu et al., 2021 [138] |
Investigate the role of gut microbiota in diabetic nephropathy. |
Donor: healthy rats. Recipient: STZ-induced rat model of DKD. |
Total of 200 uL of the suspended fecal microbiota was administered in diabetic rats by oral gavage. | FMT improved renal injury, reduced the serum acetate levels, and restored renal insulin signaling via Akt phosphorylation. | NA | NA |
| Bastos et al., 2022 [139] |
Investigate the efficacy of FMT in a model of type DKD using BTBRob/ob mice. |
Donor: BTBR wild-type mice. Recipient: BTBRob/ob mice: homozygous for the leptin gene knockout. |
FMT was administered via rectal delivery. | FMT improved body weight and glomerular hypertension and reversed IR and colon permeability. |
The treatment enriched the abundance of Odoribacteraceae. | ↓ TNF-α |
| Lauriero et al., 2021 [140] |
Explore the link between gut flora and IgA nephropathy outcome. |
Donors: healthy controls or non-progressor IgAN or progressor IgAN patients. Recipient: antibiotic-treated humanized IgAN mice. |
FMT was performed for five days. | FMT modulated renal phenotype together with BAFF levels, IR, and inflammation. | FMT modulated the proportion of Bacteroidetes, Bacteroides spp., and Actinobacteria, and increased colonization of Firmicutes. |
↓ indole ↓ pCS ↓KC |
| Emal et al., 2017 [141] |
Investigate the role of gut microbiota in kidney disease. |
Donor: untreated mouse. Recipient: AKI mouse (antibiotic-treated before I/R injury). |
FMT was performed for three days via oral gavage. | FMT modulated the expression of macrophage influx and the expression of chemokines receptors. | NA | NA |
| Nakade et al., 2018 [142] |
Explore the pathophysiologic role of microbiota associated with D–amino acids AKI. |
Donor: healthy B6 mouse. Recipient: germ-free B6 AKI mouse. |
FMT was performed for 12 weeks before I/R injury via rectal route. |
FMT protected against tubular injury in AKI mouse. | NA | NA |
| Case reports: | ||||||
| Zhao et al., 2021 [143] |
Case report of FMT treatment in two female patients with IgA nephropathy. |
Donor: male healthy donor. Recipient: female patients with IgAN with intense GI discomfort. |
FMT was performed 40 times (200 mL/day for 5 days/week) and then a further 57 times over 5 months. | FMT lowered the 24 h urinary protein and improved the protein loss. | Case 1: FMT reversed α and β diversity. Case 2: FMT decreased Verrucomicrobia. |
NA |
| Zhou et al., 2021 [144] |
Case report of FMT treatment in an adult patient with membranous nephropathy (MN). |
Donor: male healthy donor. Recipient: patient with MN. |
FMT was performed 2 times: on day 0 and after 28 days. | FMT decreased urea and creatine levels and reversed the symptoms of edema and diarrhea. | NA | NA |
| Zhi et al., 2022 [145] | Evaluate the effect of oral FMT (encapsulated FMT) on Focal Segmental Glomerulosclerosis. |
Donor: healthy donor. Recipient: CKD patient. |
Twenty FMT capsules were administered once a week for three weeks via oral capsule. | FMT ameliorated urinary proteinuria and hyperlipidemia (triglyceride and cholesterol levels). A reduced levels of proinflammatory mediators was observed in the first three month after therapy. | FMT treatment restored the balance of Prevotella coprii and Bacteroides uniformiis. | ↓ IL-5 ↓ IL-4 ↓ IL-1β |
| FMT with pre-stimulated donors: | ||||||
| Cai et al., 2020 [146] |
Determine the role of gut microbiome and resveratrol on diabetic nephropathy. |
Donor: resveratrol-treated mice or control db/m. Recipient: animal model of DN (db/db mice). |
FMT was performed by oral gavage daily for 7 days. | FMT improved renal dysfunction, intestinal permeability, and inflammation. | FMT increased Proteobacteria, Alistipes, Turicibacter, Odoribacter, and Rikenellagenus and reduced the abundance of Firmicutes, Tenericutes, Deferribacteres, and Enterococci. | ↓ TNF-α, ↓ IFN-γ, ↓ IL-6, ↓ IL-1β |
| Han et al., 2021 [147] |
Explore the protective effect of microbiome and Astragulis membranaceus on CKD. |
Donor: CKD mice treated with Astragalus membranaceus. Recipient: CKD mice (Cyclosporin A-treated). |
FMT was performed for 6 weeks. | FMT ameliorated kidney function (glomerular dysfunction, renal tubules vacuolization, and fibrosis). | FMT reversed the proportion of Akkermansia and Lactobacillus. | NA |
Abbreviations: IR, insulin resistance; CKD, chronic kidney disease; AKI, acute kidney injury; IS, Indoxyl sulfate; PHS, phenyl sulphate; HA, hippuric acid; IL; DN, diabetic mephropathy; DKD, diabetic kidney disease; STZ, streptozotocin; TMAO, Trimethylamine N-Oxide, lipopolysaccharide; SCFAs, short chain fatty acids; ESRD, end-stage renal disease; PAG, phenylacetylglutamine; PCS, P-cresyl sulfate; TGF-β1, transforming grow factor β1; IRI, ischemia reperfusion injury; TNF-α; IFN-γ, interferon-γ; PCG, p-cresyl glucuronide; BTBRob/ob mice, black and tan brachyuric obese mutant mice; IgAN, IgA nephropathy; BAFF, B cells’ activating factor; GI, gastrointestinal; MN, membranous nephropathy; and NA, not assessed.