Table 1.

Animal trials using next-generation probiotics

	Number of animals	Age	Study details	Condition of the microorganism	Method of administration	Dose	Frequency	Treatment length	Results	References
A. muciniphila ATTC BAA-835	54	6 weeks	Accelerated aging	N.A	Oral gavage	2 × 108	Three times a week	10 weeks	Improvement of immune system and gut permeability	[41]
A. muciniphila p2261	245	7 weeks	Fecal transplant from cancer patients	Live or pasteurized	Oral gavage	1 × 108–1 × 109	Three times in 2 weeks	14 days	Reduced inflammation; production of anticancer metabolites	[42]
A. muciniphila ATCC BAA-835	N.A	6–8 weeks	Acute colitis	Pasteurized and purified membrane protein	Oral gavage	1.5 × 108 of pasteurised A. muciniphila; 3 µg of Amuc_1100 protein	N.A	From 2 weeks before treatment to sacrifice	Pasteurised A. muciniphila and Amuc_1100 relieved colon shortening and splenomegaly and attenuated histological injuries in the proximal colon	[43]
A. muciniphila ATTC BAA835	24	6–7 weeks	Colitis	Live	Oral gavage	3 × 109	Daily	14 days	Colon histological damage and mucosal barrier improvement; Reduced inflammation	[44]
A. muciniphila ATTC BAA835	53	10 weeks	Obesity and type 2 diabetes	Live and heat-killed	Oral gavage	2 × 108	N.A	4 weeks	Reduced body weight, improved body composition; Improved gut barrier and metabolic parameters	[34]
A. muciniphila ATCC BAA-835	20	6 weeks	Healthy	Live	Oral gavage	2 × 108	Daily	5 weeks	Reduced fat mass and increased lean mass; Improved glucose homeostasis; Reduced metabolic endotoxemia and inflammation	[45]
A. muciniphila ATCC-BAA-835	24	6 weeks	High-fat diet	Live, supernatant or purified protein	Oral gavage	4 × 108	Daily	14 weeks	Reduced body mass; Improved glucose tolerance; increased serum concentrations of insulin and glucagon-like peptide-1 (GLP-1)	[46]
A. muciniphila ATTC BAA-835	21	8 weeks	Obese	Pasteurized	Oral gavage	2 × 108	Daily	5 weeks	Reduced body weight gain and fat mass gain without affecting cumulative food intake	[47]
A. muciniphila ATTC BAA-835	125	10–11 weeks	Obesity and diabetes	Live, pasteurized and purified protein Amuc_1100	Oral gavage	1 × 109–1 × 1010 for live Akkermansia; 1 × 1010 for pasteurized Akkermasia; 3 µg of purified protein	Daily	1st experiment 4 weeks, 2nd and 3rd experiment 5 weeks	Live and pasteurized A. muciniphila reduces body weight, fat mass gain, improve glucose intolerance and insulin resistance	[48]
A. muciniphila ATCC BAA-835	36	20 weeks	Porphiromonas gingivalis induced periodontitis	Live and purified protein Amuc_1100	Oral gavage	1 × 109	Three times a week	6 weeks	A. muciniphila and Amuc_1100 reduces alveolar bone loss and periodontal inflammation	[49]
A. muciniphila ATCC BAA-835	24	22 weeks	Obesity	Live	Oral gavage	1 × 109	Daily	2 weeks	Inflammation reduction; reduced soft and hard tissue damage and alveolar bone loss	[50]
A. muciniphila ATCC BA-835	36	6–8 weeks	Diabetes	A. muciniphila-derived extracellular vesicles	Oral gavage	10 µg	Daily	2 weeks	Reduction of gut permeability	[51]
A. muciniphila CIP 107961 T	24	25 weeks	Diabetes	Centrifugated	Oral gavage	2 × 108	Three times a week	From 3 weeks of age to 10 weeks	Delayed onset of diabetes; reduced serum endotoxin levels	[52]
A. muciniphila BAA-835	36	8 weeks	Endotoxemia-Induced Inflammation in Apoe − / −	Live and heat killed	Oral gavage	5 × 109	Daily	8 weeks	A muciniphila improved both aortic and systemic inflammation, reduced gut permeability	[53]
B. fragilis ATCC 25285	40	N.A	Graft-versus-host disease (GVHD)	Live	Oral gavage	1 × 109	Three times a week for 1 week and weekly for 30 days	33 days	Improved acute and chronic GVHD development	[54]
B. acidifaciens JCM10556	38	24 weeks	Obese	Live	Oral gavage	5 × 109	Daily	10 weeks	Reduced body weight and fat mass; Improved hepatic and peripheral insulin sensitivity	[55]
B. uniformis CECT 7771	28	6–8 weeks	High-fat diet induced obesity	Live	Oral gavage	5 × 108	Daily	7 weeks	Reduced body weight gain, liver steatosis; improved immune system and glucose oral tolerance	[56]
B. uniformis CECT 7771	30	6–8 weeks	Obese	Live	Oral gavage	5 × 107	Daily	17 weeks	Body weight and adiposity reduction; improved oral glucose tolerance; reduced gut permeability, plasma cholesterol and triglycerides	[57]
B. uniformis CECT 7771	40	6–8 weeks	Obese	Centrifuged and re-suspended in 10% skimmed milk	Oral gavage	1 × 108	Daily	14 weeks	Reduced body weight gain, plasma cholesterol, triglycerides, glucose and leptin	[58]
B. thetaiotaomicron DSM 2079	75	8 weeks	High-fat diet	Live	Oral gavage	1 × 1010	Daily	8 days	Decrease of body weight, serum triglycerides, insulin	[59]
B. thetaiotaomicron VPI-5482	60	8 weeks	High-fat diet	Live and heat killed	Oral gavage	5 × 108	Three times a week	7 weeks	Alleviated diet-induced body-weight gain and adiposity	[60]
F. prausnitzii A2–165	30	6 weeks	Asthma	Live, supernatant and dead	Oral gavage	1 × 109	Daily	22 days	Decreased inflammation; increased fecal short-chain fatty acids	[61]
F. prausnitzii A2–165 (DSM 17677) or B. thetaiotaomicron VPI-5482 (ATCC 29148)	64	N.A	Gnotobiotic animals	Live	Oral gavage	B. thetaiotaomicron 1 × 107; F. prausnitzii 7 × 109	Once a week	Until F. prausnitzii was established in a donor rat	Increased colonic mucus production	[62]
F. prausnitzii A2–165	80	6 weeks	Induced inflammation	Live	Intragastrical	1 × 109	Daily	10 days	Reduction of inflammation	[63]
F. prausnitzii ATCC 27766	60	N.A	Induced colitis	Live and supernatant concentrated	Oral gavage	1 × 109	Daily	7 days	Reduced weight loss and inflammation in colitis	[64]
F. prausnitzii A2–165	96	6–8 weeks	Induced colitis	Bacterial strains or supernatant	Intragastrical	1 × 109	Daily	7 days for sever protocol and 10 days for moderate protocol	Reduced weight loss and inflammation in colitis	[65]
F. prausnitzii ATCC27766	35	6 weeks	Induced colitis	Fresh and fresh culture supernatant	Oral gavage	1 × 109	Daily	7 days	Reduced inflammation; increased short-chain fatty acids	[66]
F. prausnitzii A2-165; HTF-F	50	2 months	Induced colitis	Live and its extracellular polymeric matrix	Intrarectal	3 × 109 of F. prausnitzii; 50 µg of its extracellular polymeric matrix	Daily	For ten days prior the DSS exposure and during the eight days of DSS treatment	Attenuated clinical symptoms in DSS-colitis; decreased inflammation	[67]
F. prausnitzii strain N.A	24	8 weeks	Diabetes	Purified microbial anti-inflammatory molecule (MAM) from F. prausnitzii	N.A	200 μL at a concentration of 1 μg/μL	Daily	4 weeks	Restoration of the intestinal barrier; decreased inflammation	[68]
F. prausnitzii strain N.A	30 calves	Newborn	Healthy	Live culture	Oral gavage and intrarectal	40 mL	One dose in the first week of life and a second dose 1 week later	2 weeks	Decreased incidence of severe diarrhea and related mortality rate	[69]
F. prausnitzii A2–165	80	6–8 weeks	Acute induced colitis	Live and supernatant	Intragastrical	1 × 109	Daily	10 days	Decreased intestinal permeability; decreased inflammation	[70]
F. prausnitzii A2–165	29	7–8 weeks	Gnotobiotic animals	Concentrated colture	Intragastrical and intrarectal	1 × 109	N.A	4 weeks	Reduced weight loss and inflammation	[71]
F. prausnitzii ATCC 27766	18	8 weeks	High-fat diet	N.A	Intragastrical	2 × 108	Twice a week every 2 weeks	13 weeks	Increased insulin sensitivity; decreased inflammation in the visceral adipose tissue	[72]
F. prausnitzii A2–165	102	N.A	Radiation-induced inflammation	Live	Intragastrical	1 × 109	Daily	6 days	Reduced severity of the histological damage and epithelial permeability	[73]
E. hallii L2–7	32	12 weeks	Obesity and diabetes	Active and heat-inactivated	Oral gavage	1 × 108	Daily	4 weeks	Reduced blood glucose levels; reduced hepatic triglyceride levels; increased fecal butyrate	[74]
C. butyricum MIYAIRI 588	18	5 weeks	High-fat diet	Spores	Oral gavage	1.4 × 109	Daily	12 weeks	Decreased plasma cholesterol levels and enhanced bile acid excretion	[75]
R. intestinalis DSMZ-14610	24	6 weeks	Induced colitis	Supernatant	Oral gavage	0.2 mL of 5× concentrated growth supernatant	Daily	7 days	Reduced intestinal inflammation; increased short-chain fatty acids	[76]
P. copri DSM 18205	12	12–14 weeks	High-fat/high-sucrose diet + fructo-oligosaccharides	Live	Oral gavage	N.A	Daily	7 days	Improved glucose homeostasis and insulin tolerance	[77]
P. copri DSM 18205	20	6–8 weeks	Healthy	Live	Oral gavage	1 × 108	Daily	4 weeks	Increased production of Th17 cells in the gut (improved immune response)	[78]
P. copri DSM 18205	10	10 to 12 weeks	High-fat diet	Live or heat-killed	Oral gavage	1 × 108	Daily	1st experiment: 7 days 2nd:7 days 3rd: single gavage	Improved of glucose tolerance only with live P. copri	[79]
P. copri CB7	12	10 weeks	High-fat diet	Live	Oral gavage	5 × 108	Twice a week	3 weeks	Increased insulin resistance	[80]
P. copri CB7	N.A	N.A	Induced colitis	Live	Oral gavage	1 × 107	Single gavage	Single gavage	Increased inflammation, more severe colitis	[81]