Table 2.

Effect and conditions of intervention with kefir bioactive compounds for different health benefits.

Health effect	Model/participants	Bioactive compound	MO1	Concentration tested	Intervention time	Effect tested/condition/bioactive compound concentration	Effect compared to control	Action mechanism	Reference
Anticarcinogenic	In vitro: MTT assay of MCF7 human breast cancer cell line	Kefiran	-	500 to 4000 μg/mL	48 h	Cell viability		-	[46]
						500 to 2000 μg/mL	↓up to 45%
						4000 μg/mL	Without effect
					72 h	500 μg/mL	Without effect
						1000 to 4000 μg/mL	↓up to 15.6%
	In vitro: MTT assay of HT-29 human colon cancer cell line	Exopolysaccharide MSR101	Lactobacillus kefiri MSR101	50 to 400 μg/mL	24 h	Cell viability	↓up to 55.9%	Upregulates the expression of apoptosis-related genes (Cyto-c, BAX, BAD, caspase 3, caspase 8, and caspase 9) in HT-29 cells	[47]
	In vitro: MTT assay of HepG2 human hepatocellular carcinoma cell line and HeLa human cervical carcinoma cell line	Kefiran	Lactobacillus kefiranofaciens	15.6 to 1000 μg/mL	24 h	Cell viability HeLa cells	↓up to 72%	Adversely affected the morphological characteristics of HeLa and HepG2 carcinoma cell lines	[48]
						HepG2 cells
						250 to 1000 μg/mL	↓up to 82%
						Below 250 μg/mL	Without effect
	In vitro: fecal water-induced DNA damage assay in HT-29 human colon cancer cell line	Lactic and acetic acids	-	20 to 200 μL/mL	30 min (preincubation)	DNA damage		Antioxidant activity	[49]
						200 μL/mL	↓ 20%
						Below 200 μL/mL	Without effect
	In vitro: cell nuclei counting assay of MCF7-E3 human breast cancer estrogen-sensitive cells	Bioactive peptides	-	0.31 to 10% (v/v)	6 days	Cell number	↓up to 88%	-	[15]
Anti-inflammatory	In vivo: DSS-induced acute colitis model in male wild-type C57BL/6 mice; chronic colitis model aggravated by Piroxicam in IL10−/− C57BL/6 mice	Extracellular vesicles (PRCC-1301 EVs)	Lactobacillus kefirgranum PRCC-1301	0.03 and 3 mg/kg bw/day	Acute colitis: from 2 days before administration of DSS to 5 days	Acute colitis		Promoting the intestinal barrier integrity through the expression of occlusion proteins (ZO-1, claudin-1, and occludin) in colon epithelial cells and inhibition of the NF-κB signaling pathway in the distal and proximal colon in an acute colitis model	[50]
						Body weight	↑16%
						Colon length (3 mg/kg bw)	↑29.6%
						Histological score	↓up to 63%
					Chronic colitis: from 14th to 28th day (Piroxicam from day 0 to day 14)	Chronic colitis
						Body weight	Without effect
						Colon length (3 mg/kg bw)	↑14.3%
						Histological score	↓up to 85.3%
	In vitro: RAW264.7 cell line (murine macrophages)	Exopolysaccharide R-17-EPS	Lactobacillus pentosus LZ-R-17	50 to 400 μg/mL	24 h	Macrophage cell viability	↑up to 38%	-	[51]
						Phagocytosis index	↑up to 44%
						Acid phosphatase activity	↑up to 78%
						NO production	↑up to 97.2%
						TNF-α
						50 and 400 μg/mL	Without effect
						100 to 200 μg/mL	↑up to 10.2%
						IL-6
						50 to 200 μg/mL	↑up to 16.7%
						400 μg/mL	↓ 9.5%
						IL-1β
						50 and 400 μg/mL	Without effect
						100 to 200 μg/mL	↑up to 14%
						IL-10
						100 to 400 μg/mL	↑up to 6.4%
						50 μg/mL	↓ 6.4%
	In vitro: DSS-induced acute colitis model in Caco-2 cell line cultures (human intestinal epithelial cells)	Extracellular vesicles	Lactobacillus kefirgranum PRCC-1301	100 μg/mL	6 h	Cytokine gene expression:		-	Kang et al. (2020) [50]
						IL-2	↓58.3%
						IL-8	↓64.3%
						TNF-α	↓67%
	In vitro: RAW264.7 cell line (murine macrophages)	Exopolysaccharide (R-5-EPS)	Lactobacillus helveticus LZ-R-5 from Tibetan kefir	50 to 400 μg/mL	24 h	Macrophage cell viability	↑up to 19%	-	[52]
						Phagocytosis index	↑up to 35.9%
						Acid phosphatase activity	↑up to 44%
						NO production	↑up to 44.4%
						TNF-α
						50 μg/mL	Without effect
						100 to 200 μg/mL	↑up to 25.5%
						400 μg/mL	↓27.5%
						IL-6	↑up to 54.3%
						IL-1β
						100 and 200 μg/mL	↑up to 20.5%
						50 and 400 μg/mL	↓up to 13.6%
						IL-10
						50 to 200 μg/mL	↑up to 18.2%;
						400 μg/mL	Without effect
	In vitro: PBMC culture isolated from human total peripheral blood	Kefiran	-	1000 and 5000 μg/mL	48 h	IL-6	Control: not detected Treatment:	-	Jenab et al. (2020) [46]
						1000 μg/mL	220 ng/L
						5000 μg/mL	270 ng/L
				500 to 4000 μg/mL	24 h, 48 h, 72 h, and 96 h	PBMC viability: 24 h
						500 to 1000 μg/mL	Without effect
						2000 to 4000 μg/mL	↑up to 200%
						48 h to 96 h	Without effect
	In vitro: TNF-α-induced intestinal inflammation model in Caco-2 cell line	Extracellular vesicles (80 to 400 nm)	Lactobacillus kefir, Lactobacillus kefiranofaciens, Lactobacillus kefirgranum	1 × 109 extracellular vesicles/mL (A strains mix ratios: 1 : 1 : 1)	24 h	IL-8		Reducing the phosphorylation of p65, a subunit of NF-κB	[53]
						mRNA level	↓up to 65.6%
						Secretion	↓up to 96.8%
	In vitro: a cell-free system containing sodium nitroprusside (10 mM)	Kefiran	-	5000 to 10.000 μg/mL	2.5 h	NO radical production	↓up to 40.91%	Nitric oxide radical scavenging capacity of kefiran	[54]
	In vitro: FliC-induced intestinal inflammation model in Caco-2 cell line	Exopolysaccharide	Lactobacillus paracasei CIDCA 8339, CIDCA 83123, and CIDCA 83124 strains	L. paracasei suspensions (OD590 0.25)	1 h (preincubation)	Promoter induction: CCL20	↓up to 55%	-	[13]
	In vivo: TNBS-induced inflammatory bowel disease in Balb/c mice	Extracellular vesicles	Lactobacillus kefir, Lactobacillus kefiranofaciens, and Lactobacillus kefirgranum	3 × 108 and 3 × 1010 extracellular vesicles/head/day (A strain mix ratios: 1 : 1 : 1)	10 days	Body weight	↑up to 12.5%	Blocking MPO activation in mouse serum	Seo et al. (2018) [53]
						Rectal bleeding severity	↓up to 75%
						Diarrheal conditions	↓up to 91.4%
						Histopathological damage	↓up to 85%
	In vitro: cell-free system	Polysaccharide extract	-	5000 μg/mL	72 h	Hyaluronidase inhibition	↓up to 35%	-	[55]
	In vitro: intestinal inflammation model in Caco-2 cell line induced by IL-1β, TNF-α, or FliC	Lactate	-	100 mM	30 min (preincubation)	Promoter inhibition CCL20		Inhibition of the NF-κB signaling pathway	[56]
						FliC-induced	↓78%
						IL-1β-induced	↓80%
						TNF-α-induced	↓42%
In vitro: peritoneal macrophages isolated from six-week Balb/c female mice	Protein (molecular mass > 30 kDa)	Lactobacillus kefiranofaciens M1	5 μL of kefir supernatant/mL	24 h	Secretion		-	[57]
					TNF-α	↑1000%
					IL-1β	↑700%
					IL-6	↑1300%
					IL-12	↑3000%
In vivo: Six- to 8-week-old BALB/c female mice	Kefiran	Lactobacillus kefiranofaciens	100 mg/kg bw/day	2, 5, or 7 days	Small intestine Mucosa		-	[58]
					IgA
					IL-10	↑up to 50%
					IL-6	↑up to 22%
					IL-12	↑up to 33%
					Fluid
					IL-4	↑up to 164%
					IL-12	↑up to 67.5%
					Large intestine
					IgA	↑up to 43%
					IgG	↑up to 41.7%
					IL-4	↑up to 44.4%
					IL-10	↑up to 47.2%
					IL-6	↑up to 30%
					IFN	↑up to 21.2%
					TNF	↑up to 20%
					Serum:
					IL-4	↑ up to 209%
					IL-6	↑ up to 254%
					IL-10	↑ up to 74.5%
					IFN	↑ up to 170%
In vivo: cotton-induced granuloma in Wistar rats	Kefiran	-	1 mL kefir suspension/day	7 days	Granuloma weight	↓44%	-	[16]
[59]	In vitro: Klebsiella pneumoniae (KP), Pseudomonas aeruginosa (PA), Bacillus cereus (BC), Staphylococcus aureus (SA), Staphylococcus epidermidis (SE), Escherichia coli (EC), clinical isolates Proteus mirabilis (PM), and Listeria monocytogenes (LM)	Lactic acid	Cow milk kefir: mesophilic aerobic bacteria, yeast, Lactobacillus, and Lactoccoccus	Cow milk kefir: 0.90% (w/w)	24 h	Microorganism growth Cow's milk kefir		-	[60]
						BC	↓132.33%
						KP	↓72.05%
						SA	↓33.33%
						SE	↓31.89%
						LM	↓16.66%
						PA	Without effect
						EC	Without effect
						PM	Without effect
			Donkey milk kefir: mesophilic aerobic bacteria, yeast, Lactobacillus, Lactoccoccus, and Leukonostoc	Donkey milk kefir: 0.80% (w/w)		Donkey milk kefir
						BC	↓183.33%
						KP	↓17.39%
						SA	↓4.34%
						SE	↓16.89%
						LM	↓58.33%
						PA	Without effect
						EC	↓33.33%
						PM	↓58.33%
	In vitro: Escherichia coli (EC), Salmonella Typhimurium (ST), and Staphylococcus aureus (SA)	Lactic, acetic, and pyruvic acids	Acetobacter orientalis, Lactococcus lactis, Lactobacillus gallinarum, Kazachstania unispora, Pichia kudriavzevii, Galactomyces candidum, Geotrichum bryndzae, Lactobacillus kefiri, and Saccharomyces cerevisiae	25, 50, 75, and 100% (v/v)	48 h	Microorganism growth		-	[14]
						EC	↓100%
						ST	↓100%
						SA	↓98.6% to 100%
	In vitro: Staphylococcus aureus (SA), Streptococcus faecalis (SF), Pseudomonas aeruginosa (PA), and Escherichia coli (EC)	Kefiran	-	1% (w/v)	24 h	Zone of inhibition Kefiran extracted by hot water			[61]
						EC	↓41.6%
						PA	↓51.3%
						SF	↓60.2%
						AS	↓61.6%
						Kefiran extracted by ultrasound
						EC	↓33.7%
						PA	↓43.0%
						SF	↓50.4%
						AS	↓51.4%
						Kefiran (hot water+ultrasound)
						EC	↓23.6%
						PA	↓32.8%
						SF	↓42.9%
						AS	↓43.4%
	In vitro: Pseudomonas aeruginosa (PA) and methicillin-resistant Staphylococcus aureus (MRSA)	FK-1000 (composed of sugars and amino acids)	Lactobacilacea, Acetobacteraceae, Pseudomonadacea, Streptococcaceae, Leuconostocaceae, Enterobacteriaceae, Alphaproteobacteria, Aeromonadaceae, and Pseudomonadales	200 μL/well of Muller Hinton	18 h	Microorganism growth pH 5		-	[62]
						MRSA	↓100%,
						PA	↓100%
						pH 7
						MRSA	↓83%
						PA	Without effect
	In vitro: Pseudomonas putida extracted from spoiled chicken	Fraction with MM < 6000 in the supernatant	Lactobacillus paracasei FX-6	0.078%, 0.156%, 0.3125%, 0.625%, 1.25%, 2.5%, 5.0%, and 10% (w/v)	21 h	Microorganism growth Pseudomonas putida 1.25% (w/v)	↓13.5% to 98%	Performance on the plasma membrane, DNA and proteins of pathogenic microorganisms	[63]
	In vitro: Escherichia coli (EC), Lactobacillus plantarum (LP), Micrococcus luteus (ML), Listeria monocytogenes (LM), Salmonella enteritidis (SE), Staphylococcus aureus (AS), and Bacillus cereus (BC)	Bacteriocin	-	100, 150, 200, and 250 μL/wells with a diameter of 7 mm	24 h	Zone of inhibition		-	[40]
						LP	↑up to 15 times
						ML	↑up to 20 times
						BC	↑up to 7 times
						LM	↑up to 14 times
						SA	↑up to 8 times
						SE	↑up to 10 times
						EC	Without effect
	In vitro: Escherichia coli (EC), Klebsiella pneumoniae (KP), Pseudomonas aeruginosa (PA), Enterococcus faecalis (EF), Bacillus cereus (BC), Bacillus subtilis (BS), and Staphylococcus aureus (SA)	Bioactive peptides	Lactobacillus, Lactococcus, and yeast	2.5% (w/v)	24 h	Antimicrobial activity		-	[64]
						SA	↑up to 100%
						EC	↑80% to 100%
						KP	↑up to 99.98%
						EF	↑94.5%to100%
						BS	↑up to 75.2%;
						PA	↑34.7% to 51%
						BC	↑up to 12.2%
	In vitro: Listeria monocytogenes (LM) and Salmonella enteritidis (SE)	Exopolysaccharide DN1	Lactobacillus kefiranofaciens DN1	0.35, 1% and 2.5% (w/v)	24 h	Microorganism growth 0.3% (w/v)		-	[65]
						LM	↓56%
						SE	↓5.45%
						1% and 2.5% (w/v)
LM						↓100%
SE						↓100%
In vitro: Escherichia coli (EC), Bacillus cereus (BC), and Salmonella enteritidis (SE)	Lactic Acid	-	25, 50, 75, and 100% (v/v)	24 h	Microorganism growth 50-100% (v/v)		-	[66]
					EC	↓31% to 99%
					SE	↓up to 98.7%
					BC	↓up to 87%
					25% (v/v)
					SE	↑6%
					BC	↑24%
In vitro: methicillin-resistant Staphylococcus aureus (MRSA) (S547)	Biofilms	Lactobacillus plantarum	106 CFU/mL	12, 24, 36, 48, 60, 72, and 84 h	Microorganism growth MRSA	↓1.4% to 30%	Inhibition of biofilm production by MRSA	[67]
In vitro: Escherichia coli (EC)	F1 bioactive peptide	Lactobacillus paracasei subsp. Tolerans FX-6	0.00625% (w/v)	20 h	Microorganism growth EC	↓33% to 57%	Damage to the outer and inner cell membrane with extravasation of potassium ions and cytoplasmic β-galactosidase; binding to the bacterial DNA	[68]
In vitro: Escherichia coli (EC), Klebsiella pneumoniae (KP), Pseudomonas aeruginosa (PA), Salmonella Typhymurium (ST), and Staphylococcus aureus (SA)	Kefiran	Lactobacillus kefiranofaciens	1% (w/v)	13 h	Microorganism growth		-	[69]
					EC	↓up to 25.2%
					PA	↓up to 19%
					KP	↓up to 9.2%
					ST	↓up to 3.3%
					AS	↓up to 2%
In situ (whey fermented with kefir grains): Aspergillus flavus (AFL), Penicillium crustosum (PC), Aspergillus terreus (AT), Aspergillus Fumigatus (AF), Trichoderma longibrachiatum (TL), Rhizopus sp., and Aspergillus parasiticus (AP)	Lactic and acetic acids	-	95% (v/v)	24 h	Microorganism germination		-	[70]
					Rhizopus sp.	↓70%
					AP	↓67
					TL	↓61%
					AF	↓60%
					AFL	↓34%
					PC	Without effect
					AT	Without effect
In vitro: spent culture supernatant (SCS) obtained from Clostridium difficile	Thermolabile fraction > 10 kDa in the supernatant	-	OD 550 = 1	1 h	Biological activity of C. difficile SCS on Vero cells Supernatant from Lactococcus lactis subps. lactis or from a mixture of all microorganisms of kefir	↓80%	-
					Supernatant from Lactobacillus kefir, Lb. plantarum, Saccharomyces cerevisiae, and Kluyveromyces marxianus	Without effect
In vitro: Streptococcus faecalis (SF), Pseudomonas aeruginosa (PA), Salmonella Typhi (STP), Bacillus subtilis (BS), Bacillus cereus (BC), Escherichia coli (EC), Klebsiella pneumoniae (KP), Staphylococcus aureus (SA), and Fusarium graminearum (FG) Aspergillus flavus AH3 (mycelial dry weights and aflatoxin B1)	Kefiran	-	0.1 mL/5 mm diameter paper disks 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, and 10% (v/v)	24 h for bacteria and yeasts and 7 days for fungi 10 days	Zone of inhibition		-	[71]
					STP	↑75%
					SF	↑66.6%
					BC	↑62.5%
					PA	↑50%
					BS	↑44.4%
					EC	↑37.5%
					SA	↑16.6%
					FG	↑15.4%
					KP	↑9.09%
					Aflatoxin B1	↓33.3% to 100%
					Mycelial dry weights	↓14.9% to 100%
In vitro: Salmonella Typhimurium (ST), Escherichia coli (EC), Pseudomonas aeruginosa (PA), and Staphylococcus aureus (SA)	Lactic acid (partial effect)	-	0.9% (w/w)	24 h	Zone of inhibition		-	[17] – Industrial kefir
					ST	↓60%
					SA	↓56.6%
					EC	↓56.5%
					PA	Without effect
				48 h	ST	↓41.4%
					SA	↓42.1%
					EC	Without effect
					PA	Without effect
				7 days	ST	↓1.67%
					SA	Without effect
					EC	Without effect
					PA	Without effect
In vitro: Salmonella enteritidis (SE)	S-layer proteins	Lactobacillus kefir strains CIDCA 8344 and CIDCA 8348	2 × 108 CFU/mL	4 h	Microorganism growth S-layer proteins from L. kefir 8348		-	[72]
					Salmonella enteritidis	↓up to 99.96%
					S-layer proteins from L. kefir 8344
					Salmonella enteritidis	↓50% to 99.93%
In situ (kefir-fermented milk): spores and vegetative cells de Bacillus cereus and toxin production by B. cereus	Organic acids	-	1% and 5% (w/v)	24 h	1% (w/v)		Reduction of the biological activity of the pathogenic microorganism	[31]
					Vegetative cells	↓70% to 98%
					Number of spores	↓up to 80 times
					5% (w/v)
					Vegetative cells	↓70% to 99.8%
					Number of spores	↓from 80 to 50,000 times
Antioxidant	In vitro: 2,2-diphenyl-1-picrylhydrazyl—DPPH; reduce Fe3+ to Fe2+ (FRAP)	Kefiran	-	0.08%, 0.04%, 0.02%, 0.01%, and 0.005% (w/v)	30 min	DPPH	↓25 to 85%	-	[61]
						FRAP	↓37 to 84%
	In situ (cow milk kefir): 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid—ABTS; oxygen radical absorbance capacity—ORAC	Bioactive peptides	-	-	-	ABTS	↑35.8%	The antioxidant effect cannot be attributed to the ion chelating ability	[14]
				20 μL/well (v/v)	80 min	ORAC	↑111.6%
	In vitro: ascorbic acid equivalent reducing capacity (AAEC)	Kefiran	-	1% and 0.5% (w/v)	20 min	Ascorbic acid equivalent reducing capacity	Control (hyaluronic acid) Without effect Treatment	Metal chelating activity and sequestering activity of hydroxyl and superoxide radical	[54]
						0.5% (w/v)	4.44 μg/mL
						1% (w/v)	8.47 μg/mL
	In situ (cow and ewe milk kefirs) 2,2′-Azino-bis-3-ethylbenzothiazoline-6-sulfonic acid—ABTS 2,2-Diphenyl-1-picrylhydrazyl—DPPH Reduce Fe3+ to Fe2+ (FRAP)	Total phenolic compounds	-	5% (v/v) 8.3% (v/v) 8.3% (v/v)	3 min 30 min 30 min	Ewe milk kefir		-	[73, 74] – Industrial kefir
						ABTS	↓4.6% to 46%
						DPPH	↓20% to 50%
						FRAP	↑24% to 134%
						Cow milk kefir
						ABTS	↓52% to 70%
						DPPH	↑70% to 220%
						FRAP	↑13% to 120%
	In vitro 2,2′-Azino-bis-3-ethylbenzothiazoline-6-sulfonic acid–ABTS 2,2-Diphenyl-1-picrylhydrazyl–DPPH	Bioactive peptides	-	0.625% (w/v)	6, 30, 60, 90, 150, and 180 min	ABTS	↑2% to 25.6%	-	[64]
				2.5%, 1.25%, 0.62, and 0.31% (w/v)	120 min	DPPH
						2.5% peptides 1.25% peptides	↓2.64% to 17.7%
						7 days	↑2.99%
						14 days	↓0.3% to 6.32%
						0.62% peptides
						7 days	↓1.15% to 11.03%
						From 14 days	↑13.22% to 18.85%
						0.31% peptides	↓17.0% to 30.0%
	In vitro: 2,2-diphenyl-1-picrylhydrazyl—DPPH	Exopolysaccharides	Bacillus amyloliquefaciens, Uncultured Bacillus sp. clone, Bacillus subtilis, Bacillus subtilis, Bacillus tequilensis, and ↓Bacillus siamensis	1 mL (109 CFU/mL)/3 mL	30 min	Antioxidant activity	↑10% to 20%	Resistance to hydrogen peroxide	[73]
	In vitro: 2,20-azobis(2-methypropionamidine) dihydrochloride)—APPH—in bovine serum albumin (BSA)	Exopolysaccharides	Acetobacter okinawensis, Leuconostoc pseudomesenteroides, and Kazachstania unispora	0.05%, 0.1%, 0.15%, 0.20%, and 0.25% (w/v)	360 min	AAPH-oxidized BSA protein	↓31% to 96%	-	[28]
	In situ (cow milk kefir): 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid—ABTS	Exopolysaccharides	-	0.00113% (w/v)	6 min	Antioxidant activity	↑8.43%	-	[74]
	In situ (goat milk kefir): 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid—ABTS; oxygen radical absorbance capacity—ORAC	Phenolic compounds	-	38.93, 61.60, 26.62, and 123.23% (w/v)	-	ABTS	↑62% to 120%	-	[75]
						ORAC	↑10% to 40%
Cholesterol	In-vitro: exopolysaccharides (EPSs) in DMEM medium containing 3T3-L1 adipocytes	Exopolysaccharides	Lactobacillus kefiri (LKDH1, LKDH3, and LKDH5 strains) and Leuconostoc mesenteroides (LMDH4, LMDH6, LMDH7, LMDH8, and LMDH9 strains)	0.01 mg/mL, 0.1 mg/mL, and 0.2 mg/mL of exopolysaccharides isolated from their producer microorganisms	6 days	Lipid accumulation in adipocytes		-	[76]
						0.01 mg/dL LMDH4	↓12%
						Other strains	Without effect
						0.1 mg/dL
						LMDH4	↓22%
						LMDH7	↓24%
						LKDH5	↓14%
						Other strains	Without effect
						0.2 mg/dL
						LMDH7	↓28%
						LDMH4	↓22%
						LKDH3	↓22%
						LKDH5	↓19%
						LMDH6	↓10%
						Other strains	Without effect
	In vivo: C57BL/6J high-fat and high-fructose diet-induced obese mice and with oral administration of heat-killed lactic acid bacteria (HLAB) from kefir	Exopolysaccharides	Leuconostoc mesenteroides LMDH4 and Lactobacillus kefiri LKDH5	10 mL/kg bw of a mixture Leuconostoc mesenteroides LMDH4 (1 × 1010 CFU/mL) and Lactobacillus kefiri LKDH5 (1 × 109 CFU/mL)	8 weeks	Total cholesterol	Without effect	Reduction in the proinflammatory genes expression (Hp and Wfdc21) and genes (Fabp4 and Fasn) related to the synthesis of fatty acids in the adipose tissues	[76]
						HDL	Without effect
						LDL	Without effect
						Triglyceride	Without effect
						Adipose tissue weight	↓36%
	In vitro: Lactococcus lactis WH-C1 from kefir in GM17 broth supplemented with cholesterol (30 mg/100 mL)	Exopolysaccharides	Lactococcus lactis WH-C1	4% (v/v) inoculum Lactococcus lactis WH-C1 from Tibet kefir grains	24 h	Cholesterol in the medium	↓up to 31.23%	-	[77]
Blood pressure	In situ (cow milk kefir): assay of inhibitory activity on angiotensin-converting enzyme (ACE)	Bioactive peptides	-	11.2 mg/100 mL	24 h	ACE activity	↓98.4%	-	[14]
Glucose	In vivo: C57BL/6J high-fat and high-fructose diet-induced obese mice and with oral administration of heat-killed lactic acid bacteria (HLAB) from kefir	Exopolysaccharides	Leuconostoc mesenteroides LMDH4 and Lactobacillus kefiri LKDH5	10 mL/kg bw of a mixture Leuconostoc mesenteroides LMDH4 (1 × 1010 CFU/mL) and Lactobacillus kefiri LKDH5 (1 × 109 CFU/mL)	8 weeks	Plasma glucose	Without effect	-	[76]
	In vivo: Streptozotocin-nicotinamide- (STZ-NA-) induced diabetic rats/male rats of 8-12 weeks old	Alcohol and phenolic compounds	-	5 to 20 mL kefir with black rice extract (1 : 1)/kg bw	4 weeks	Number of Langerhans islet	↑up to 199%	Proton-radical scavenging activity	[78]
						Insulin-positive β-cells	↑up to 2330%
Intestinal microbiota modulation	In vitro: fecal samples from healthy children aged between 8 months and 3 years old	Exopolysaccharides 8339 and 83124	L. paracasei CIDCA 8339 and CIDCA 83124	0.3% (w/v)	72 h	L. paracasei CIDCA 8339		-	[79]
						Lentisphaerae	↑32%
						Firmicutes	↑12%
						Victivallis	↑33%
						Acidaminococcu	↑15%
						Comamonas	↑6%
						Proteobacteria	↓31%
						Bacteroidetes	↓11%
						Actinobacteria	↓1.5%
						L. paracasei CIDCA 83124
						Proteobacteria	↑15%
						Comamonas	↑52%
						Firmicutes	↓17%
						Bacteroidetes	↓10%
						Actinobacteria	↓1.3%
						Escherichia	↓28%
						Bacteroides	↓11% to 12%
						Klebsiella	↓6%
	In vivo: thirty 16-week-old female C57BL/6J ovariectomized mice	Bioactive peptides	-	100 mg of bioactive peptides/kg bw	56 days	Firmicutes/Bacteroidetes	↑17%	-	[80]
						Alloprevotella	↑326%
						Romboustsia	↓85%
						Anaerostipes	↓66%
						Ruminococcus	↓55%
						Parasutterella	↓46%
						Streptococcus	↓39%
	In vivo: male Balb/c mice aged 16 weeks	Exopolysaccharide	Lactobacillus kefiranofaciens XL10	0.4 mL of an XL10 suspension (108 CFU/mL)	21 days	Firmicutes/Bacteroidetes	↑0.04% to 1.8%	-	[81]
						Lactobacillaceae	↑14.59%
						Ruminococcaceae (day 7)	↑15.12%
						Bifidobacteriaceae	↑0.2% to 0.59%
						Rikenellaceae	↓2.63% to 2.74%
						Abundance in the gender	↓ up to 39.19%
	BALB/c female mice (6 to 8 weeks old)	Kefiran	-	Daily intake 0.75 to 1 mg kefiran per day	21 days	Bifidobacteria	↑ up to 17%	-	[82]
	In vitro: Bifidobacterium bifidum PRL2010	Kefiran	-	0.3% (w/v)	72 h	Bifidobacterium bifidum PRL2010	Control (MRSc without carbon source) Without growth Treatment 5.8 × 108 CFU/mL	Enhanced transcription of genes that act as effector molecules in the microbe-host interaction, such as pili; transcription of genes involved in the metabolism of diet glucans	[41]
Nervous system	In vitro: MTT assay of PC12 cell line (from rat adrenal gland -phaeochromocytoma)	Kefiran	-	5 and 10%	1 to 6 days	Cell viability		-	[46]
						1 day	↓up to 26.7%
						2 days	Without effect
						4 days (10%)	↓15.4%
						6 days (10%)	↓21.2%
	In vivo: aging mouse model induced with D-galactose (oxidative stress)	Exopolysaccharide	Lactobacillus plantarum YW11	Low dose: 20 mL/kg bw/day of 1 mg/mL EPS solution High dose: 20 mL/kg bw/day of 2.5 mg/mL EPS solution	12 weeks	Low dose		Modulation of gut microbiota and reduction of oxidative stress of the intestinal tract (decrease of NOx fecal content and increase of content of short-chain fatty acids—acetic and butyric)	[83]
						T-AOC	↑27.7%
						MDA	Without effect
						GSH-Px	Without effect
						SOD	Without effect
						CAT	Without effect
						High dose
						T-AOC	↑38.18%
						MDA	↓49.6%
						GSH-Px	↑21.55%
						SOD	↑33.14%
						CAT	↑61.09%
Osteoporosis	In vivo: thirty 16-week-old female C57BL/6J ovariectomized mice	Bioactive peptides (KPS)	-	100 mg of KPs/kg bw	56 days	Trabecular bone volume	↑264%	-	[80]
						Trabecular number	↑235%
						Bone mineral density	↑41%
						Mechanical properties	↑42%
						Hardness of the bones	↑36%
						Trabecular separation areas	↓36.5%
						Nanoindentation areas	↓33%

¹Producer microorganism. ↑: increase; ↓: decrease; EPS: exopolysaccharide; IL: interleukin; TNF-α: tumor necrosis factor-α; IFN: interferon; ZO-1: zonula occludens-1; NO: nitric oxide; PBMC: peripheral blood mononuclear cell; DSS: dextran sulfate sodium; TNBS: 2,4,6-trinitrobenzene sulfonic acid; FliC: flagellin; DO: optical density; CCL20: chemokine-ligand-20; bw: body weight; MPO: myeloperoxidase; MDA: malondialdehyde; GSH-Px: glutathione peroxidase; SOD: superoxide dismutase; CAT: catalase; T-AOC: total antioxidant capacity; MTT: (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl); Cyto-c: cytochrome c; BAX: BCL2-associated X; BAD: BCL2-associated agonist of cell death.