Review Article

Bioactive Compounds from Kefir and Their Potential Benefits on Health: A Systematic Review and Meta-Analysis

Table 2

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

Health effectModel/participantsBioactive compoundMO1Concentration testedIntervention timeEffect tested/condition/bioactive compound concentrationEffect compared to controlAction mechanismReference

AnticarcinogenicIn vitro: MTT assay of MCF7 human breast cancer cell lineKefiran-500 to 4000 μg/mL48 hCell viability-[46]
500 to 2000 μg/mL↓up to 45%
4000 μg/mLWithout effect
72 h500 μg/mLWithout effect
1000 to 4000 μg/mL↓up to 15.6%
In vitro: MTT assay of HT-29 human colon cancer cell lineExopolysaccharide MSR101Lactobacillus kefiri MSR10150 to 400 μg/mL24 hCell 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 lineKefiranLactobacillus kefiranofaciens15.6 to 1000 μg/mL24 hCell 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/mLWithout effect
In vitro: fecal water-induced DNA damage assay in HT-29 human colon cancer cell lineLactic and acetic acids-20 to 200 μL/mL30 min (preincubation)DNA damageAntioxidant activity[49]
200 μL/mL↓ 20%
Below 200 μL/mLWithout effect
In vitro: cell nuclei counting assay of MCF7-E3 human breast cancer estrogen-sensitive cellsBioactive peptides-0.31 to 10% (v/v)6 daysCell number↓up to 88%-[15]
Anti-inflammatoryIn vivo: DSS-induced acute colitis model in male wild-type C57BL/6 mice; chronic colitis model aggravated by Piroxicam in IL10-/- C57BL/6 miceExtracellular vesicles (PRCC-1301 EVs)Lactobacillus kefirgranum PRCC-13010.03 and 3 mg/kg bw/dayAcute colitis: from 2 days before administration of DSS to 5 daysAcute colitisPromoting 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 weightWithout 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-EPSLactobacillus pentosus LZ-R-1750 to 400 μg/mL24 hMacrophage 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/mLWithout 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/mLWithout 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 vesiclesLactobacillus kefirgranum PRCC-1301100 μg/mL6 hCytokine 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 kefir50 to 400 μg/mL24 hMacrophage 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/mLWithout 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/mLWithout effect
In vitro: PBMC culture isolated from human total peripheral bloodKefiran-1000 and 5000 μg/mL48 hIL-6Control: not detected Treatment:-Jenab et al. (2020) [46]
1000 μg/mL220 ng/L
5000 μg/mL270 ng/L
500 to 4000 μg/mL24 h, 48 h, 72 h, and 96 hPBMC viability: 24 h
500 to 1000 μg/mLWithout effect
2000 to 4000 μg/mL↑up to 200%
48 h to 96 hWithout effect
In vitro: TNF-α-induced intestinal inflammation model in Caco-2 cell lineExtracellular vesicles (80 to 400 nm)Lactobacillus kefir, Lactobacillus kefiranofaciens, Lactobacillus kefirgranum extracellular vesicles/mL (A strains mix ratios: 1 : 1 : 1)24 hIL-8Reducing 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/mL2.5 hNO 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 lineExopolysaccharideLactobacillus paracasei CIDCA 8339, CIDCA 83123, and CIDCA 83124 strainsL. paracasei suspensions ( 0.25)1 h (preincubation)Promoter induction: CCL20↓up to 55%-[13]
In vivo: TNBS-induced inflammatory bowel disease in Balb/c miceExtracellular vesiclesLactobacillus kefir, Lactobacillus kefiranofaciens, and Lactobacillus kefirgranum and extracellular vesicles/head/day (A strain mix ratios: 1 : 1 : 1)10 daysBody weight↑up to 12.5%Blocking MPO activation in mouse serumSeo 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 systemPolysaccharide extract-5000 μg/mL72 hHyaluronidase inhibition↓up to 35%-[55]
In vitro: intestinal inflammation model in Caco-2 cell line induced by IL-1β, TNF-α, or FliCLactate-100 mM30 min (preincubation)Promoter inhibition CCL20Inhibition 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 miceProtein ( kDa)Lactobacillus kefiranofaciens M15 μL of kefir supernatant/mL24 hSecretion-[57]
TNF-α↑1000%
IL-1β↑700%
IL-6↑1300%
IL-12↑3000%
In vivo: Six- to 8-week-old BALB/c female miceKefiranLactobacillus kefiranofaciens100 mg/kg bw/day2, 5, or 7 daysSmall 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 ratsKefiran-1 mL kefir suspension/day7 daysGranuloma 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 acidCow milk kefir: mesophilic aerobic bacteria, yeast, Lactobacillus, and LactoccoccusCow milk kefir: 0.90% (w/w)24 hMicroorganism growth
Cow’s milk kefir
-[60]
BC↓132.33%
KP↓72.05%
SA↓33.33%
SE↓31.89%
LM↓16.66%
PAWithout effect
ECWithout effect
PMWithout effect
Donkey milk kefir: mesophilic aerobic bacteria, yeast, Lactobacillus, Lactoccoccus, and LeukonostocDonkey milk kefir: 0.80% (w/w)Donkey milk kefir
BC↓183.33%
KP↓17.39%
SA↓4.34%
SE↓16.89%
LM↓58.33%
PAWithout effect
EC↓33.33%
PM↓58.33%
In vitro: Escherichia coli (EC), Salmonella Typhimurium (ST), and Staphylococcus aureus (SA)Lactic, acetic, and pyruvic acidsAcetobacter orientalis, Lactococcus lactis, Lactobacillus gallinarum, Kazachstania unispora, Pichia kudriavzevii, Galactomyces candidum, Geotrichum bryndzae, Lactobacillus kefiri, and Saccharomyces cerevisiae25, 50, 75, and 100% (v/v)48 hMicroorganism 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 hZone 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 Pseudomonadales200 μL/well of Muller Hinton18 hMicroorganism growth
pH 5
-[62]
MRSA↓100%,
PA↓100%
pH 7
MRSA↓83%
PAWithout effect
In vitro: Pseudomonas putida extracted from spoiled chickenFraction with in the supernatantLactobacillus paracasei FX-60.078%, 0.156%, 0.3125%, 0.625%, 1.25%, 2.5%, 5.0%, and 10% (w/v)21 hMicroorganism 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 mm24 hZone 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
ECWithout 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 peptidesLactobacillus, Lactococcus, and yeast2.5% (w/v)24 hAntimicrobial 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 DN1Lactobacillus kefiranofaciens DN10.35, 1% and 2.5% (w/v)24 hMicroorganism 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 hMicroorganism 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)BiofilmsLactobacillus plantarum106 CFU/mL12, 24, 36, 48, 60, 72, and 84 hMicroorganism growth
MRSA
↓1.4% to 30%Inhibition of biofilm production by MRSA[67]
In vitro: Escherichia coli (EC)F1 bioactive peptideLactobacillus paracasei subsp.
Tolerans FX-6
0.00625% (w/v)20 hMicroorganism 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)KefiranLactobacillus kefiranofaciens1% (w/v)13 hMicroorganism 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 hMicroorganism germination-[70]
Rhizopus sp.↓70%
AP↓67
TL↓61%
AF↓60%
AFL↓34%
PCWithout effect
ATWithout effect
In vitro: spent culture supernatant (SCS) obtained from Clostridium difficile kDa in the supernatant-1 hBiological 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 marxianusWithout 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 hZone of inhibition-[17] – Industrial kefir
ST↓60%
SA↓56.6%
EC↓56.5%
PAWithout effect
48 hST↓41.4%
SA↓42.1%
ECWithout effect
PAWithout effect
7 daysST↓1.67%
SAWithout effect
ECWithout effect
PAWithout effect
In vitro: Salmonella enteritidis (SE)S-layer proteinsLactobacillus kefir strains CIDCA 8344 and CIDCA 8348 CFU/mL4 hMicroorganism 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. cereusOrganic acids-1% and 5% (w/v)24 h1% (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
AntioxidantIn 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 minDPPH↓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—ORACBioactive peptides---ABTS↑35.8%The antioxidant effect cannot be attributed to the ion chelating ability[14]
20 μL/well (v/v)80 minORAC↑111.6%
In vitro: ascorbic acid equivalent reducing capacity (AAEC)Kefiran-1% and 0.5% (w/v)20 minAscorbic acid equivalent reducing capacityControl (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 minABTS↑2% to 25.6%-[64]
2.5%, 1.25%, 0.62, and 0.31% (w/v)120 minDPPH
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—DPPHExopolysaccharidesBacillus amyloliquefaciens, Uncultured Bacillus sp. clone, Bacillus subtilis, Bacillus subtilis, Bacillus tequilensis, and ↓Bacillus siamensis1 mL (109 CFU/mL)/3 mL30 minAntioxidant activity↑10% to 20%Resistance to hydrogen peroxide[73]
In vitro: 2,20-azobis(2-methypropionamidine) dihydrochloride)—APPH—in bovine serum albumin (BSA)ExopolysaccharidesAcetobacter okinawensis, Leuconostoc pseudomesenteroides, and Kazachstania unispora0.05%, 0.1%, 0.15%, 0.20%, and 0.25% (w/v)360 minAAPH-oxidized BSA protein↓31% to 96%-[28]
In situ (cow milk kefir): 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid—ABTSExopolysaccharides-0.00113% (w/v)6 minAntioxidant activity↑8.43%-[74]
In situ (goat milk kefir): 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid—ABTS; oxygen radical absorbance capacity—ORACPhenolic compounds-38.93, 61.60, 26.62, and 123.23% (w/v)-ABTS↑62% to 120%-[75]
ORAC↑10% to 40%
CholesterolIn-vitro: exopolysaccharides (EPSs) in DMEM medium containing 3T3-L1 adipocytesExopolysaccharidesLactobacillus 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 microorganisms6 daysLipid accumulation in adipocytes-[76]
0.01 mg/dL LMDH4↓12%
Other strainsWithout effect
0.1 mg/dL
LMDH4↓22%
LMDH7↓24%
LKDH5↓14%
Other strainsWithout effect
0.2 mg/dL
LMDH7↓28%
LDMH4↓22%
LKDH3↓22%
LKDH5↓19%
LMDH6↓10%
Other strainsWithout 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 kefirExopolysaccharidesLeuconostoc mesenteroides LMDH4 and Lactobacillus kefiri LKDH510 mL/kg bw of a mixture Leuconostoc mesenteroides LMDH4 ( CFU/mL) and Lactobacillus kefiri LKDH5 ( CFU/mL)8 weeksTotal cholesterolWithout effectReduction 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]
HDLWithout effect
LDLWithout effect
TriglycerideWithout effect
Adipose tissue weight↓36%
In vitro: Lactococcus lactis WH-C1 from kefir in GM17 broth supplemented with cholesterol (30 mg/100 mL)ExopolysaccharidesLactococcus lactis WH-C14% (v/v) inoculum Lactococcus lactis WH-C1 from Tibet kefir grains24 hCholesterol in the medium↓up to 31.23%-[77]
Blood pressureIn situ (cow milk kefir): assay of inhibitory activity on angiotensin-converting enzyme (ACE)Bioactive peptides-11.2 mg/100 mL24 hACE activity↓98.4%-[14]
GlucoseIn vivo: C57BL/6J high-fat and high-fructose diet-induced obese mice and with oral administration of heat-killed lactic acid bacteria (HLAB) from kefirExopolysaccharidesLeuconostoc mesenteroides LMDH4 and Lactobacillus kefiri LKDH510 mL/kg bw of a mixture Leuconostoc mesenteroides LMDH4 ( CFU/mL) and Lactobacillus kefiri LKDH5 ( CFU/mL)8 weeksPlasma glucoseWithout effect-[76]
In vivo: Streptozotocin-nicotinamide- (STZ-NA-) induced diabetic rats/male rats of 8-12 weeks oldAlcohol and phenolic compounds-5 to 20 mL kefir with black rice extract (1 : 1)/kg bw4 weeksNumber of Langerhans islet↑up to 199%Proton-radical scavenging activity[78]
Insulin-positive β-cells↑up to 2330%
Intestinal microbiota modulationIn vitro: fecal samples from healthy children aged between 8 months and 3 years oldExopolysaccharides 8339 and 83124L. paracasei CIDCA 8339 and CIDCA 831240.3% (w/v)72 hL. paracasei CIDCA 8339-[79]
Lentisphaerae↑32%
Firmicutes↑12%
Victivallis↑33%
Acidaminococcu↑15%
Comamonas6%
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 miceBioactive peptides-100 mg of bioactive peptides/kg bw56 daysFirmicutes/Bacteroidetes↑17%-[80]
Alloprevotella↑326%
Romboustsia↓85%
Anaerostipes↓66%
Ruminococcus↓55%
Parasutterella↓46%
Streptococcus↓39%
In vivo: male Balb/c mice aged 16 weeksExopolysaccharideLactobacillus kefiranofaciens XL100.4 mL of an XL10 suspension (108 CFU/mL)21 daysFirmicutes/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 day21 daysBifidobacteria↑ up to 17%-[82]
In vitro: Bifidobacterium bifidum PRL2010Kefiran-0.3% (w/v)72 hBifidobacterium bifidum PRL2010Control (MRSc without carbon source)
Without growth
Treatment
 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 systemIn vitro: MTT assay of PC12 cell line (from rat adrenal gland -phaeochromocytoma)Kefiran-5 and 10%1 to 6 daysCell viability-[46]
1 day↓up to 26.7%
2 daysWithout effect
4 days (10%)↓15.4%
6 days (10%)↓21.2%
In vivo: aging mouse model induced with D-galactose (oxidative stress)ExopolysaccharideLactobacillus plantarum YW11Low 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 weeksLow doseModulation 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%
MDAWithout effect
GSH-PxWithout effect
SODWithout effect
CATWithout effect
High dose
T-AOC↑38.18%
MDA↓49.6%
GSH-Px↑21.55%
SOD↑33.14%
CAT↑61.09%
OsteoporosisIn vivo: thirty 16-week-old female C57BL/6J ovariectomized miceBioactive peptides (KPS)-100 mg of KPs/kg bw56 daysTrabecular 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.