THERAPEUTIC IndEx GAStroenteroloGy pag. 5 OUROUR PRPROBIOTICOOBIOTTIC ImmunoloGy pag. 17

DermAtoloGy pag. 21 STRAINSSTRRAINSS

AntI-AGInG pag. 23

CArDIoloGy/ metAbolISm pag. 27

DIetetICS pag. 29

GIneColoGy pag. 31 uroloGy pag. 39

Gut-brAIn pag. 43 Probiotics like nobody else OurOur IInnovativennovative orAl CAre pag. 47 Probiotical S.p.A. Via E. Mattei, 3, 28100 Novara (NO), Italy - T: +39 0321 46 59 33 61 Strains:Sttrains:i F: +39 0321 49 26 93 - email: [email protected] - www.probiotical.com teChnoloGIeS pag. 49 ReadyReaddy fforor YourYour HealthHeallth tHeraPeUtiC index

GastroenteroloGy pag. 5

ImmunoloGy pag. 17

DermatoloGy pag. 20 antI-aGInG pag. 22

CarDIoloGy/metabolIsm pag. 25

DIetetICs pag. 27

GIneColoGy pag. 29 uroloGy pag. 37

Gut-braIn pag. 41 oral Care pag. 44 teChnoloGIes pag. 45 Romane Catalogo Indice 13-5-20:Layout 1 26/05/20 17:44 Pagina 1

Probiotical is driving probiotics innovation since 1985. Our expertise comprises strain selection, advanced R&D, production of strains to finished products with all guarantees of stability and demonstrated efficacy in many functionalities.

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StrainS & blendS index

Bifidobacterium • Bifidobacterium breve - BR03™ (DSM 16604) Gastroenterology: Strain: pag. 8, 15 - Blend: pag. 5, 6, 8, 10, 14 ; Dermatology: Blend: pag. 21 ; Dietetics: Strain: pag. 27 - Blend: pag. 27 ; • Bifidobacterium adolescentis - BA02 (DSM 18351, formerly Urology: Strain: pag. 35, 38 ; Gut-brain : Strain: pag 42 - Blend: pag 43 ALB 1) Gastroenterology: Blend: pag. 8 • Bifidobacterium breve - B632™ (DSM 24706) • Bifidobacterium animalis subsp. lactis - BA05 Gastroenterology: Blend : pag. 5, 6 ; Immunology: Blend : pag. 19 ; (DSM 18352) Gynecology: Strain: pag. 35 Urology: Strain: pag. 38

• Bifidobacterium animalis subsp. lactis - Bb1 • Bifidobacterium breve - MB113 (DSM 23732) (DSM 17850) Anti-aging: Strain: pag. 23 ; Gynecology: Cardiology/metabolism: Strain: pag 25 - Blend: pag 25 Strain: pag. 35 ; Urology: Strain: pag. 39, 40 • Bifidobacterium infantis - BI02 (DSM 24687, formerly MB287) Cardiology/metabolism: Strain: pag. 26 • Bifidobacterium animalis subsp. lactis - BS01™ (LMG P-21384) Gastroenterology: Strain: pag. 7 , • Bifidobacterium longum - W11 (LMG P-21586) Blend: pag. 8 , Immunology: Strain pag. 18 - Blend: pag. 17 ; Gastroenterology: Strain: pag. 9; Gut-brain : Strain: pag 43 Dermatology: Blend: pag. 20 ; Anti-aging: Strain: pag. 22 ; • - BL03 (DSM 16603) Gastroenterology: Gut-brain : Strain: pag. 42 - Blend: pag. 43 Bifidobacterium longum Blend: pag. 8 , Urology: Strain : pag. 40 ; Gut-brain : Blend: pag 43

• Bifidobacterium animalis subsp. lactis - BS05 • Bifidobacterium longum - 04 (DSM 23233) (DSM 23032) Anti-aging: Strain: pag. 22 Cardiology/metabolism: Blend: pag. 25 ; Dietetics: Strain: pag. 28 ; Gut-brain : Blend: pag. 41 • Bifidobacterium animalis subsp. lactis - BS07 (MB 2409) Cardiology/metabolism: Strain: pag. 25 • Bifidobacterium longum - DLBL07 (DSM25669) Anti-aging: Blend: pag. 24 • Bifidobacterium animalis subsp. lactis - MB2409 (DSM 23733) Cardiology/metabolism: Blend: pag. 25 • Bifidobacterium longum - DLBL08 (DSM 25670) Anti-aging: Blend: pag. 24 • Bifidobacterium bifidum - BB01 (DSM 22892) Gastroenterology: Strain: pag. 13 • Bifidobacterium longum - DLBL09 (DSM 25671) Anti-aging: Blend: pag. 24

• Bifidobacterium bifidum - BB06 (MB 107) • Bifidobacterium longum - DLBL10 (DSM 25672) Cardiology/metabolism: Strain: pag. 25 Anti-aging: Blend: pag. 24

• Bifidobacterium bifidum - MB109 (DSM 23731) • Bifidobacterium longum - DLBL11 (DSM 25673) Cardiology/metabolism: Strain: pag. 25 - Blend: pag. 25 Anti-aging: Blend: pag. 25 Lactobacillus • Limosilactobacillus fermentum - LF5 (CNCM I-789) (API) (formerly Lactobacillus fermentum ) Gastroenterology: Strain: pag. 16 ; Gynecology: Strain: pag. 29, 34 • Lactobacillus acidophilus - LA02 (DSM 21717) Gastroenterology: Strain: pag. 13, 15 - Blend: pag. 10 ; • Limosilactobacillus fermentum - LF08 (DSM 18297) Gynecology: Blend: pag. 31 ; Urology: Strain: pag. 38 ; (formerly Lactobacillus fermentum ) Gynecology: Strain: pag. 29 Gut-brain : Strain: pag 40, 42 • Limosilactobacillus fermentum - LF09 (DSM 18298) • Lactobacillus acidophilus - LA06 (DSM 23033) (formerly Lactobacillus fermentum ) Gastroenterology : Strain: pag. 16 ; Gynecology: Strain: pag. 29 Anti-aging: Strain: pag. 22

• Lactobacillus acidophilus - CRL1294 (DSM 24513) • Limosilactobacillus fermentum - LF10 (DSM 19187) (formerly Lactobacillus fermentum ) Gastroenterology : Strain: pag. 16 ; (under worldwide exclusive license from the CERELA) Gynecology: Strain: pag. 30 - Blend: pag. 31, 34 ; Gut-brain : Blend: pag. 42 Gynecology: Strain: pag. 31 • Limosilactobacillus fermentum - LF11 (DSM 19188) • - LC03 (DSM 27537) Lacticaseibacillus casei (formerly Lactobacillus fermentum ) Gastroenterology : Strain: pag. 16 ; (formerly Lactobacillus casei ) Gynecology: Strain: pag. 30 Gastroenterology: Strain: pag. 13 • Limosilactobacillus fermentum - LF15 (DSM 26955) • Lactobacillus crispatus - LCR01 (DSM 24619) (formerly Lactobacillus fermentum ) Gynecology: Blend: pag. 34 Gynecology: Strain: pag. 36 • Limosilactobacillus fermentum - LF16 (DSM 26856) • Lactobacillus crispatus - CRL1251 (DSM 24438) (formerly Lactobacillus fermentum ) Gynecology: Strain: pag. 30 ; (under worldwide exclusive license from the CERELA) Gut-brain : Blend: pag. 41 Gynecology: Strain: pag. 33 • Limosilactobacillus fermentum - ME-3 (DSM 14241) • Lactobacillus crispatus - CRL1266 (DSM 24439) (formerly Lactobacillus fermentum ) Cardiology/metabolism: Strain: pag. 26 (under worldwide exclusive license from the CERELA) • Lactobacillus gasseri - LGS06 (DSM 32405) Gynecology: Strain: pag. 33 Dietetics: Strain: pag. 28 ; Gynecology: Strain: pag. 36 • Lactobacillus delbrueckii subsp. bulgaricus - LDB01 • Lactobacillus gasseri - CRL1259 (DSM 24512) (DSM 16606) Gastroenterology : Strain: pag. 13 (under worldwide exclusive license from the CERELA) • Lactobacillus delbrueckii subsp. delbrueckii - LDD01 Gynecology: Strain: pag. 33 (DSM 22106) Gastroenterology : Strain: pag. 5 , 14 - Blend: pag. 6,12 ; • Lacticaseibacillus paracasei - LPC00 (LMG P-21380) Urology: Strain: pag. 38 ; Gut-brain : Blend: pag. 42 ; (formerly Lactobacillus paracasei ) Gastroenterology : Strain: pag. 13 ; Oral care : Blend: pag. 44 Immunology: Blend: pag. 19

• Limosilactobacillus fermentum - LF5 (CNCM I-789) • Lacticaseibacillus paracasei - LPC09 (DSM 24243) (formerly Lactobacillus fermentum ) (formerly Lactobacillus paracasei ) Gastroenterology : Strain: pag. 15 ; Gastroenterology : Strain: pag. 16 ; Gynecology: Strain: pag. 29, 34 Urology: Strain: pag. 28 - Blend: pag. 37 , 39 Romane Catalogo Indice 13-5-20:Layout 1 26/05/20 17:44 Pagina 5

• Lacticaseibacillus paracasei subsp. paracasei - • Lacticaseibacillus rhamnosus - LR05 (DSM 19739) CRL1289 (DSM 24440) (formerly Lactobacillus paracasei ) (formerly Lactobacillus rhamnosus ) (under worldwide exclusive license from the CERELA) Immunology: Blend: pag. 17 ; Dermatology: Blend: pag. 20 Gynecology: Strain: pag. 33 • Lacticaseibacillus rhamnosus - LR06 (DSM 21981) • Lactiplantibacilluspentosus - LPS01 (DSM 21980) (formerly Lactobacillus rhamnosus ) (formerly Lactobacillus pentosus ) Gastroenterology : Strain: pag. 14 - Blend: pag. 12 ; Urology: Gastroenterology : Strain: pag. 14 - Blend: pag. 12 ; Anti-aging: Strain: pag. 37 ; Oral care : Blend: pag. 44 Strain: pag. 22 ; Urology: Strain: pag. 35 ; Gut-brain : Blend: pag 41 - Strain: pag. 42 ; Oral care : Blend: pag. 44 • Lactiplantibacillus plantarum - LP01™ (LMG P-21021) (formerly Lactobacillus plantarum ) Gastroenterology : Strain: pag. 7, • Lactobacillus salivarius - CRL1328 (DSM 24441) 14, 15 - Blend: pag. 6, 8, 10, 12 ; Immunology: Blend: pag. 17, 19 ; (under worldwide exclusive license from the CEntro Anti-aging: Strain : pag. 22 ; Gynecology: Blend: pag. 34 ; Urology: de REferencia para LActobacilos, Argentina) Strain: pag. 40 - Blend: pag. 37, 40 ; Gut-brain : Strain: pag. 42 - Gastroenterology : Strain : pag.16 ; Gynecology: Strain: pag. 31 ; Blend: pag. 41, 42 ; Oral care : Blend: pag. 44 Urology: Strain: pag. 38 • Lactiplantibacillus plantarum - LP02 (LMG P-21020) (formerly Lactobacillus plantarum ) • Lactobacillus salivarius - LS01™ (DSM 22775) Gastroenterology : Strain: pag. 14 ; Immunology: Blend: pag. 17 ; Gastroenterology: Strain: pag. 15 ; Immunology: Blend: pag. 19 ; Gynecology: Blend: pag. 34 ; Urology: Strain: pag. 37 Dermatology: Strain: pag. 20 - Blend: pag. 21 ; Anti-aging: Strain: pag. 22 ; Gut-brain : Strain: pag. 42 • Lactiplantibacillus plantarum - LP09 (DSM 25710) (formerly Lactobacillus plantarum ) Gastroenterology : Strain: pag. 14 • Lactobacillus salivarius - LS03 (DSM 22776) • Limosilactobacillus reuteri - Lb26 (DSM 16341) Dermatology: Strain: pag. 21 ; Gut-brain : Blend: pag 42 (formerly Lactobacillus reuteri ) Anti-aging: Strain: pag. 23 ; Urology: • Lactococcus lactis - LLC02 (DSM 29536) Strain: pag. 39 Gastroenterology: Blend: pag. 6 • Limosilactobacillus reuteri - LRE02 (DSM 23878) (formerly Lactobacillus reuteri ) Gastroenterology : Strain: pag. 15 , Immunology: Strain: pag. 18 ; Gynecology: Strain: pag. 35 ; Urology: Strain: pag. 40 Streptococcus • Lacticaseibacillus rhamnosus - GG (ATCC 53103) • - FP4 (DSM 18616) (formerly Lactobacillus rhamnosus ) Streptococcus thermophilus Gastroenterology : Strain: pag. 11 ; Immunology: Strain: pag. 18 ; Dietetics: Blend: pag. 27 Gut-brain : Strain: pag. 42 - Blend: pag 43 ; Oral care : Strain: pag. 44 • Streptococcus thermophilus - YO8 (DSM 17843) • Lacticaseibacillus rhamnosus - LR04 (DSM 16605) Gastroenterology : Strain: pag. 13 (formerly Lactobacillus rhamnosus ) Gastroenterology : Strain: pag. 11, 14, 15, 16 ; Immunology: • Streptococcus thermophilus - ST10 (DSM 25246) Blend: pag. 17 ; Urology: Blend: pag. 37 Gastroenterology : Strain: pag. 13 c i BR03™ (DSM 16604) l

Bifidobacterium breve - o c + y

Bifidobacterium breve - B632™ (DSM 24706) New Study b a

DAILY DOSAGE IN CLINICAL STUDY 1,3) 100 million CFU each + 100 million CFU each FINISHED DOSAGE FORM b

-

FUNCTIONALITY Gaseous colic • Prevention of gastrointestinal symptoms • Rebalance of the intestinal microbiota in children and in infants y • Inhibition of Enterobacteriaceae and of other coliforms isolated from colicky infants g o l

SCIENTIFIC SUPPORT o r

Human clinical trials In vitro studies e t

1) Bona G. et al. The association of BR03 and B632 is effective to pre- a) Simone M. et al. The Probiotic Bifidobacterium breve B632 Inhibited n

vent colics in bottle-fed infants: a pilot, controlled, randomized and dou - the Growth of Enterobacteriaceae within Colicky Infant Microbiota Cultu - e o

ble blind study. Published in J Clin Gastroenterol, 2016. res. BioMed Research International 1- 6, 2014. r t

2) Aloisio I. et al. Three-Month Feeding Integration With Bifidobacterium b) Aloisio I. et al. Characterization of Bifidobacterium spp. strains for the s Strains Prevents Gastrointestinal Symptoms in Healthy Newborns. Fron - treatment of enteric disorders in newborns. Appl Microbiol Biotechnol a tiers in Nutrition, May 2018, art. 39. 2012, 96:1561–1576. G 3) Mogna L. et al. Capability of the Two Microorganisms Bifidobacterium c) Nicola S. et al. Interaction between probiotics and human immune breve B632 and Bifidobacterium breve BR03 to Colonize the Intestinal cells: the prospective anti-inflammatory activity of Bifidobacterium breve Microbiota of Children J Clin Gastroenterol, 2014. Suppl. 1, November/ BR03. AgroFOOD, 2010; 21(2):S44-47. December, Vol. 48. d) Mogna L. et al. Assessment of the In Vitro Inhibitory Activity of Specific See next page for other studies on this combination in celiac disease Probiotic Bacteria Against Different Escherichia coli strains. J Clin Ga - stroenterol. 2012; 46 Suppl.S29-32. e) Del Piano M. et al. In Vitro Sensitivity of Probiotics to Human Pancrea - tic Juice. J Clin Gastroenterol. Vol 42, Suppl. 3, Part 2, Sept. 2008. (DSM 20074 was re-deposited as 22106).

Lactobacillus delbrueckii subsp. delbrueckii - LDD01 (DSM 22106) FINISHED DOSAGE FORM FUNCTIONALITY Gaseous colic • Inhibition of E. coli , including toxinogenic O157:H7 • Inhibition of Klebsiella pneumoniae and of different coliforms isolated from colicky infants SCIENTIFIC SUPPORT In vitro studies c) Mogna L. et al. In Vitro Inhibition of Klebsiella pneumoniae by Lacto - a) Savino F. et al. Antagonistic effect of Lactobacillus strains against gas- bacillus delbrueckii subsp. delbrueckii LDD01 (DSM 22106): An Inno - producing coliforms isolated from colicky infants. BMC Microbiology vative Strategy to Possibly Counteract Such Infections in Humans? J Clin 2011, 11:157. Gastroenterol. 2016 Nov/Dec;50 Suppl 2, Proceedings from the 8th Pro- b) Mogna L. et al. Assessment of the In Vitro Inhibitory Activity of Specific biotics, Prebiotics & New Foods for Microbiota and Human Health mee - Probiotic Bacteria Against Different Escherichia coli strains. J Clin Ga - ting held in Rome, Italy on September 13-15, 2015:S136-S139. stroenterol. 2012;46 Suppl.S29-32.

5 e BR03™ (DSM 16604) s Bifidobacterium breve - a e

+ s i

Bifidobacterium breve - B632™ (DSM 24706) d

c

DAILY DOSAGE IN CLINICAL STUDY 1) 100 million CFU + 100 million CFU • 2-4) 1 billion CFU + 1 billion CFU FINISHED DOSAGE FORM a i l FUNCTIONALITY e

Decrease inflammation in celiac disease C

- SCIENTIFIC SUPPORT Human clinical trials 3) Quagliariello A. et al. Effect of Bifidobacterium breve on the Intestinal y g

1) Mogna L. et al. Capability of the two microorganisms B632 and BR03 Microbiota of Coeliac Children on a Gluten Free Diet: A Pilot Study. Nu - o l

to colonize the intestinal microbiota of children. J Clin Gastroenterol. trients. 2016 Oct 22;8(10). pii:E660. o 2014; 48 Suppl:S37-39. r 4) Primec M. et al. Clinical intervention using Bifidobacterium strains in e t

2) Klemenak M. et al. Administration of decreases the production of celiac disease children reveals novel microbial modulators of TNF- a and n

TNF- α in children with celiac disease. Dig Dis Sci (2015). short-chain fatty acids. Clinical Nutrition 2018, 1-9. e o r t s a G Lactiplantibacillus plantarum - LP01™ (LMG P-21021) (formerly Lactobacillus plantarum )

Lactococcus lactis - LLC02 (DSM 29536) New Studies n o i t a Lactobacillus delbrueckii subsp. delbrueckii - LDD01 (DSM 22106) r a

• • p

DAILY DOSAGE IN CLINICAL STUDY 1 billion cells 800 million cells 200 million cells RAW MATERIAL e AND FINISHED DOSAGE FORM r p

FUNCTIONALITY Opposing dysbiosis and improving symptoms such as abdominal pain and bloating in patients l with Inflammatory bowel diseases, in patients having undergone abdominal surgery and in patients after colonoscopy e w o b SCIENTIFIC SUPPORT /

Human clinical trial 3) Bonavina L, Ariani A, Ficano L, Iannuzziello D, Pasquale L, Aragona y r

1) Bonavina L, Arini A, Ficano L, Iannuzziello D, Pasquale L, Aragona SE, SE, Drago L, Ciprandi G, On Digestive Disorders ISG. Lactobacillus e g

Ciprandi G, On Digestive Disorders ISG. Abincol® ( Lactobacillus plantarum plantarum LP01, Lactobacillus lactis subspecies cremoris LLC02, and r u s

LP01, Lactobacillus lactis subspecies cremoris LLC02, Lactobacillus del - Lactobacillus delbrueckii LDD01) in patients undergoing bowel pre - l brueckii LDD01), an oral nutraceutical, pragmatic use in patients with chro - paration. Acta Biomed. 2019 Jul 10;90(7-S):13-17. a n nic intestinal disorders. Acta Biomed. 2019 Jul 10;90(7-S):8-12. i

In vitro studies m

2) Bonavina L, Arini A, Ficano L, Iannuzziello D, Pasquale L, Aragona SE, o

Ciprandi G, On Digestive Disorders ISG. Post-surgical intestinal dysbiosis: Mogna L. et al. Assessment of the In Vitro Inhibitory Activity of Specific d b

Probiotic Bacteria Against Different Escherichia coli strains. J Clin Ga - a use of an innovative mixture ( Lactobacillus plantarum LP01, Lactobacillus / lactis subspecies cremoris LLC02, Lactobacillus delbrueckii LDD01). Acta stroenterol. 2012;46 Suppl.S29-32. D

Biomed. 2019 Jul 10;90(7-S):18-23. b I

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BR03™ (DSM 16604) o Bifidobacterium breve - i t

DAILY DOSAGE IN CLINICAL STUDY 1) 10 billion CFU (uncoated) • 2) 5 billion CFU uncoated and RAW MATERIAL a p AND FINISHED DOSAGE FORM i

1 billion cells microencapsulated t s

• • • • n

FUNCTIONALITY Constipation Intestinal transit Anti-inflammatory Reduction of gastro-intestinal discomfort Inhibition of pathogenic E. coli o C SCIENTIFIC SUPPORT / S b

Human clinical trials In vitro studies I

1) Del Piano M. et al. The use of probiotics in the treatment of constipa - a) Mogna L. et al. Assessment of the In Vitro Inhibitory Activity of Specific -

tion in the elderly CIBUS, 2005; 1(1):23-30. Probiotic Bacteria Against Different Escherichia coli strains. J Clin Ga - y

2) Del Piano M. et al. Evaluation of the intestinal colonization by micro - stroenterol. 2012;46 Suppl.S29-32. g o encapsulated probiotic bacteria in comparison with the same uncoated b) Nicola S. et al. Interaction between probiotics and human immune l o

strains. J Clin Gastroenterol. 2010; 44 Suppl 1:S42-6. cells: the prospective anti-inflammatory activity of Bifidobacterium breve r

BR03. AgroFOOD, 2010; 21(2):S44-47. e t

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Juice. J Clin Gastroenterol. Vol 42, Suppl. 3, Part 2, Sept. 2008. (DSM e o

20074 was re-deposited as 22106). r t s a Bifidobacterium longum - BL03 (DSM 16603) G Lactiplantibacillus plantarum - LP01™ (LMG P-21021) (formerly Lactobacillus plantarum ) Bifidobacterium animalis subsp. lactis - BS01™ (LMG P-21384) Bifidobacterium adolescentis - BA02 (DSM 18351, formerly ALB 1) Bifidobacterium breve - BR03™ (DSM 16604) DAILY DOSAGE IN CLINICAL STUDY 10 billion CFU RAW MATERIAL AND FINISHED DOSAGE FORM FUNCTIONALITY Constipation • Intestinal transit

SCIENTIFIC SUPPORT Human clinical trial In vitro studies Del Piano M. et al. The use of probiotics in the treatment of constipation a) Del Piano M. et al. In Vitro Sensitivity of Probiotics to Human Pancreatic in the elderly (BL03, LP01, BS01, LR05, BA02 and BR03 seperately). Juice (LA02, LPC00, LP01, LR04, BR03, BL03 and BA02). J Clin Ga - CIBUS, 2005; 1(1):23-30. stroenterol. Vol 42, Suppl. 3, Part 2, Sept. 2008. b) Rossi M. et al. fermentation of fructooligosaccharides and inulin by Bifidobacteria : a comparative study of pure and fecal cultures (BA02). Applied and Environmental Microbiology, 2005;71(10):6150-6158.

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Gastroenterology - IbS/SUDD/ Constipation Lactiplantibacillus plantarum - LP01™ (LMG P-21021) (formerly Lactobacillus plantarum) Bifidobacterium breve - BR03™ (DSM 16604) + New Study DAILY DOSAGE IN CLINICAL STUDY • 1) 5 billion CFU + 5 billion CFU RAW MATERIAL AND FINISHED DOSAGE FORM • 2) 5 billion CFU / strain (uncoated form) vs. 1 billion cells/strain (microencapsulated form)

• 3-4) 2.5 billion CFU + 2.5 billion CFU • 5) 10 billion CFU IbS/Constipation

FUNCTIONALITY IBS • Constipation • Intestinal transit • Reduction of gastro-intestinal discomfort • Reduction of inflammation • Inhibition of E. coli, including toxinogenic O157:H7

SCIENTIFIC SUPPORT Human clinical trials In vitro studies 1) Saggioro A. Probiotics in the treatment of Irritable Bowel Syndrome. a) Mogna L. et al. Assessment of the in vitro inhibitory activity of specific J Clin Gastroenterol, 2004; 38(8): S104-106. probiotic bacteria against different Escherichia coli strains. J Clin Gastro- 2) Del Piano et al. Evaluation of the intestinal colonization by microen- enterol. 2012; 46 Suppl:S29-32. capsulated probiotic bacteria in comparison to the same uncoated b) Nicola S. et al. Interaction between probiotics and human immune strains. J Clin Gastroenterol, 2010; 44(8):S42-46. cells: the prospective anti-inflammatory activity of Bifidobacterium breve

3) Del Piano M. et al. The use of probiotics in healthy volunteers with eva- BR03. AgroFOOD, 2010; 21(2):S44-47. - Gastroenterology cuation disorders and hard stools. A double blind, randomized, placebo- controlled study. J Clin Gastroenterol, 2010; 44(8): S30-34. c) Amoruso A. et al. (2019) A Systematic Evaluation of the Immunomo- dulatory and Functional Properties of Probiotic Bifidobacterium Breve 4) Dimidi E. et al. The effect of probiotics on functional constipation in adults: a systematic review and meta-analysis of randomized controlled BR03 (DSM 16604) Lactobacillus Plantarum LP01 (LMG P-21021). J trials. Am J Clin Nutr 2014;100:1075–84. Prob Health. 7:214. 5) Del Piano M. et al. The use of probiotics in the treatment of constipa- Internal data in vitro on gut permeability avaiable upon request tion in the elderly (BL03, LP01, BS01, LR05, BA02 and BR03 sepera- tely). CIBUS, 2005; 1(1):23-30.

Lactiplantibacillus plantarum - LP01™ (LMG P-21021) (formerly Lactobacillus plantarum) Lactobacillus acidophilus - LA02 (DSM 21717) + DAILY DOSAGE IN CLINICAL STUDY 5 billion CFU + 5 billion CFU RAW MATERIAL AND FINISHED DOSAGE FORM FUNCTIONALITY IBS • Reduction of gastro-intestinal discomfort • Reduction of inflammation

SCIENTIFIC SUPPORT Human clinical trial In vitro study Saggioro A. Probiotics in the treatment of Irritable Bowel Syndrome. J Nicola S. et al. Immunomodulation properties of Lactobacillus plantarum LP01 Clin Gastroenterol, 2004; 38(8): S104-106. (LMG P-21021) and Lactobacillus acidophilus LA02 (DSM 21717) blend. Internal data in vitro on gut permeability and anti-inflammatory activity available upon request. 10 L s A O S S D F F L 2 2 1 b o H t U U r C C ) y A 0 ) l n u u

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Lacticaseibacillus rhamnosus - LR06 (DSM 21981) (formerly Lactobacillus rhamnosus ) P P / t r

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DAILY DOSAGE IN CLINICAL STUDY 1,2) LR06 3 billion CFU + LPS01 3 billion CFU + LP01 3 billion CFU + FINISHED DOSAGE FORM i t LDD01 1 billion CFU 500 million CFU • 3) 1.5 billion CFU per strain s e t n i

FUNCTIONALITY Gastric barrier function • Improvement of the incidence and severity of bad breath (halitosis) – see section oral health o r t s

SCIENTIFIC SUPPORT a G

Human clinical trials In vitro studies - 1) Del Piano M. et al. The Innovative Potential of Lactobacillus rhamnosus a) Mogna L. et al. In Vitro Inhibition of Klebsiella pneumoniae by Lacto - y

LR06, Lactobacillus pentosus LPS01, Lactobacillus plantarum LP01 and bacillus delbrueckii subsp. delbrueckii LDD01 (DSM 22106): An Inno - g

Lactobacillus delbrueckii subsp. delbrueckii LDD01 to Restore the Ga - vative Strategy to Possibly Counteract Such Infections in Humans? J Clin o l

stric Barrier Effect” in Patients Chronically Treated with PPIs – a Pilot Gastroenterol. 2016 Nov/Dec;50 Suppl 2, Proceedings from the 8th o Study. J Clin Gastroenterol 2010;46:S18-S26. Probiotics, Prebiotics & New Foods for Microbiota and Human Health r e meeting held in Rome, Italy on September 13-15, 2015:S136-S139. t

2) Del Piano M. et al. Correlation Between Chronic Treatment With Proton n

Pump Inhibitors (PPIs) and Bacterial Overgrowth in the Stomach – Any b) Mogna L. et al. Assessment of the in vitro inhibitory activity of specific e o

Possible Beneficial Role for Selected Lactobacilli ? J Clin Gastroenterol probiotic bacteria against different Escherichia coli strains. J Clin Gastro - r t

2014;48:S40-S46. enterol. 2012; 46 Suppl:S29-32. s

3) Del Piano M. et al. Correlation Between Specific Bacterial Groups in a the Oral Cavity and the Severity of Halitosis: any Possible Beneficial Role G for Selected Lactobacilli ? J Gastroint Dig Syst, 2014; 4:197.

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probiotic bacteria against different Escherichia coli strains. J Clin Gastro - o r enterol. 2012; 46 Suppl:S29-32. t s a Lactobacillus delbrueckii subsp. delbrueckii - LDD01 (DSM 22106) G FINISHED DOSAGE FORM FUNCTIONALITY Inhibition of E. coli , including enterohemorrhagic O157:H7 • Inhibition of Klebsiella pneumoniae and of different coliforms isolated from colicky infants SCIENTIFIC SUPPORT In vitro studies novative Strategy to Possibly Counteract Such Infections in Humans? a) Mogna L. et al. Assessment of the in vitro inhibitory activity of spe - J. Clin Gastroenterol. 2016 Nov/Dec; 50 Suppl 2. cific probiotic bacteria against different Escherichia coli strains. J Clin c) Savino F. et al. Antagonistic effect of Lactobacillus strains against Gastroenterol. 2012; 46 Suppl:S29-32. gas-producing coliforms isolated from colicky infants. BMC Microbio - b) Mogna L. et al. In Vitro Inhibition of Klebsiella pneumoniae by Lac - logy 2011, 11:157. tobacillus delbrueckii subsp. delbrueckii LDD01 (DSM 22106): An In -

Lactiplantibacillus plantarum - LP09 (DSM 25710) (formerly Lactobacillus plantarum ) RAW MATERIAL FUNCTIONALITY Anti-pathogen activity AND FINISHED DOSAGE FORM

SCIENTIFIC SUPPORT Internal data available upon request

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FINISHED DOSAGE FORM FINISHED DOSAGE FORM n a

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SCIENTIFIC SUPPORT y

In vitro study g o Deidda F. et al. The In Vitro Effectiveness of Lactobacillus fermentum l o

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SCIENTIFIC SUPPORT In vitro study Ocana V. et al. Characterization of a bacteriocin like substance produced by a vaginal Lactobacillus salivarius strain. Applied and Environmental Microbiology, 1999; 65(12):5631-5635.

Lacticaseibacillus rhamnosus - LR04 (DSM 16605) (formerly Lactobacillus rhamnosus ) RAW MATERIAL FUNCTIONALITY Inhibition of Klebsiella pneumoniae and E. coli AND FINISHED DOSAGE FORM

SCIENTIFIC SUPPORT In vitro studies 2) Mogna L. et al. Assessment of the in vitro inhibitory activity of specific 1) Mogna L. et al. In Vitro Inhibition of Klebsiella pneumoniae by Lactoba - probiotic bacteria against different Escherichia coli strains (LP01, LP02, cillus delbrueckii subsp. delbrueckii LDD01 (DSM 22106). An Innovative LR04, LR06, LPS01, LDD01, BR03, B632). J Clin Gastroenterol. 2012; Strategy to Possibly Counteract Such Infections in Humans? J Clin Gastro - 46 Suppl:S29-32. enterol, Vol 50, Supp. 2, November/December 2016. + Internal data on immune stimulation and anti-pathogen activity available upon request for certain strains

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Limosilactobacillus reuteri - LRE02 (DSM 23878) (formerly Lactobacillus reuteri ) RAW MATERIAL FUNCTIONALITY Production of reuterin and vitamin B12 • Anti-Pathogen activity AND FINISHED DOSAGE FORM

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Ligilactobacillus salivarius - LS01™ (DSM 22775) i t (formerly Lactobacillus salivarius ) a m r

DAILY DOSAGE IN CLINICAL STUDY 1,2,3) 2 billion CFU FINISHED DOSAGE FORM e d

4) 5 billion CFU + 2 billion CFU of Streptococcus thermophilus ST10 c + Tara gum i p o FUNCTIONALITY Treatment of atopic dermatitis • Improvement of the Quality of Life in subjects with Atopic Dermatitis t A

• •

Skin health Inhibition of C. acnes (formerly classified as P. acnes )–induced IL-8 release -

SCIENTIFIC SUPPORT y g

Human clinical trials In vitro studies o l

1) Drago L. et al. Effects of Lactobacillus salivarius LS01 (DSM 22775) a) Drago L. et al. Strain-dependent release of cytokines modulated by o treatment on adult atopic dermatitis: a randomized placebo-controlled Lactobacillus salivarius human isolates in an in vitro model. BMC Res t a study. Int J Immunopathol Pharmacol. 2011; 24(4):1037-48. Notes. 2010; 3:44. m 2) Drago L. et al. Changing of fecal flora and clinical effect of L. salivarius b) Deidda F. et al. New Approach in Acne Therapy, A Specific Bacte - r e LS01 in adults with atopic dermatitis. J Clin Gastroenterol. 2012; 46 riocin Activity and a Targeted Anti IL-8 Property in Just 1 Probiotic D Suppl:S56-63. Strain, the L. salivarius LS03. (LS01, LS02, LS03) J Clin Gastroenterol 3) Niccoli A. et al. Preliminary results on clinical effects of probiotic Lac - 2018;52:S78-S81. tobacillus salivarius LS01 in children affected by atopic dermatitis. J Clin Gastroenterol. 2014; 48 Suppl:S34-36. 4) Drago L. et al. Treatment of atopic dermatitis eczema with a high con - centration of Lactobacillus salivarius LS01 associated with an innovative gelling complex. J Clin Gastroenterol. 2014; 48 Suppl:S47-511.

Bifidobacterium animalis subsp. lactis - BS01™ (LMG P-21384) + Lacticaseibacillus rhamnosus - LR05 (DSM 19739) (formerly Lactobacillus rhamnosus ) DAILY DOSAGE IN CLINICAL STUDY 1 billion cells each + 2.5 g FOS RAW MATERIAL AND FINISHED DOSAGE FORM FUNCTIONALITY Atopic dermatitis

SCIENTIFIC SUPPORT Human clinical trial Manzotti G. et al. Probiotics as a Novel Adjuvant Approach to Atopic Dermatitis. Journal of Contemporary Immunology (2014) Vol. 1 No. 2 pp. 57-66. + Immunomodulation in vitro data available upon request

20 a i Ligilactobacillus salivarius - LS01™ (DSM 22775) (formerly Lactobacillus salivarius ) r a c i t Bifidobacterium breve - BR03™ (DSM 16604) + r u

c

DAILY DOSAGE IN CLINICAL STUDY 1,3,4) 2 billion CFU + 2 billion CFU LS01 + BR03. FINISHED DOSAGE FORM i n

2) 1 billion CFU + 1 billion CFU o r h c

FUNCTIONALITY • Reduce frequency, duration and intensity of Atopic Dermatitis symptoms Improvement of the Quality of Life in subjects with ,

Atopic Dermatitis (AD) • Rosacea • Chronic urticaria • Skin health a e c a

SCIENTIFIC SUPPORT s o R

Human clinical trials In vitro studies - 1) Iemoli E. et al. Probiotics reduce gut microbial translocation and improve a) Deidda F. et al. New Approach in Acne Therapy: A Specific Bacte - y

adult atopic dermatitis. J Clin Gastroenterol. 2012; 46 Suppl:S33-40. riocin Activity and a Targeted Anti IL-8 Property in Just 1 Probiotic g

Strain, the L. salivarius LS03. J Clin Gastroenterol. 2018 May 18. o 2) Licari A. et al. Efficacia clinica di Lactobacillus salivarius LS01 e Bifido - l bacterium breve BR03 in pazienti pediatrici affetti da dermatite atopica. Il b) Drago L. Immunomodulatory Effects of Lactobacillus salivarius LS01 o t medico pediatra 2016;38-42. and Bifidobacterium breve BR03, alone and in combination, on Peri - a

3) Nettis E. et al. Probiotics and refractory chronic spontaneous urticaria. pheral Blood Mononuclear Cells of Allergic Asthmatics. Allergy Asthma m Immunol Res. 2015 July; 7(4):409-413. r Eur Ann Allergy Immunol 2016, Vol 48, N 5, 182-187. e

4) Fortuna M. C. et al. A case of Scalp Rosacea treated with low dose do - D xycycline and probiotic therapy and literature review on therapeutic options. Dermatologic Therapy ISSN 1396-0296; DOI:10.1111/12355.

+ Refer to precedent page for additional studies on LS01 alone in atopic dermatitis e

Ligilactobacillus salivarius - LS03 (DSM 22776) n c A (formerly Lactobacillus salivarius ) -

RAW MATERIAL y

FUNCTIONALITY Acne - Anti-pathogen activity: inhibition of C. acnes (formerly classified as P. acnes ) and its AND FINISHED DOSAGE FORM g

induction of IL-8 • Immunomodulation • Strong adhesion to the intestinal mucosa o l o SCIENTIFIC SUPPORT: t a In vitro study m

Deidda F. et al. New Approach in Acne Therapy: A Specific Bacteriocin r Activity and a Targeted Anti IL-8 Property in Just 1 Probiotic Strain, the L. e salivarius LS03. J Clin Gastroenterol. 2018 May 18. D

21

t

BS05 (DSM 23032) n Bifidobacterium animalis subsp. lactis - a d i x

Lactobacillus acidophilus - LA06 (DSM 23033) o i t

FINISHED DOSAGE FORM n A •

FUNCTIONALITY Antioxidant activity Reduced glutathione (GSH) and increased superoxide dismutase production -

SCIENTIFIC SUPPORT g n In vitro and animal model studies i g

Amaretti A. et al. Antioxidant properties of potentially probiotic bacteria: in a - vitro and in vivo activities. Appl Microbiol Biotechnol. 2013; 97(2):809-17. i t n A Ligilactobacillus salivarius - LS01™ (DSM 22775) New data (formerly Lactobacillus salivarius ) FINISHED DOSAGE FORM Lactiplantibacillus plantarum - LP01™ (LMG P-21021) (formerly Lactobacillus plantarum ) Lacticaseibacillus rhamnosus - LR06 (DSM 21981) (formerly Lactobacillus rhamnosus )

Bifidobacterium animalis subsp. lactis - BS01™ (LMG P-21384) New data RAW MATERIAL AND FINISHED DOSAGE FORM FUNCTIONALITY Antioxidant activity • Reduced glutathione (GSH) and increased superoxide dismutase production

SCIENTIFIC SUPPORT Internal in vitro data available upon request on above-mentioned functions and strains

22

t

Lb26 (DSM 16341) (formerly Lactobacillus reuteri ) n Limosilactobacillus reuteri - a d (under worldwide exclusive license from BIOMAN for nutraceutical and pharma applications) i x o i

RAW MATERIAL t

AND FINISHED DOSAGE FORM n •

FUNCTIONALITY Carrier of selenium with high bioavailability Organic selenium from probiotic strain allergen A

free with High Bioavailability: Protection of DNA, proteins and lipids from oxidative damage -

g

SCIENTIFIC SUPPOR n In vitro studies c) Galano E. et al. Privileged Incorporation of Selenium as Selenocysteine i g

a) Mogna L. et al. Selenium and zinc internalized by Lactobacillus buchneri in Lactobacillus reuteri Proteins Demonstrated by Selenium-specific Ima - a - i

Lb26 (DSM 16341) and Bifidobacterium lactis Bb1 (DSM 17850): impro - ging and Proteomics. Molecular & Cellular Proteomics 12.8, 2013. t ved bioavailability using a new biological approach. J Clin Gastroenterol. d) Mangiapane E. et al. Selenium effects on the metabolism of a Se-meta - n 2012; 46 Suppl:S41-5. bolizing Lactobacillus reuteri : analysis of envelope-enriched and extracel - A b) Mangiapane E. et al. An integrated proteomic and physiological appro - lular proteomes. The Royal Society of Chemistry, 2014. ach to understand the adhesion mechanism of the probiotic Lactobacillus e) Mangiapane E. et al. Selenium and Selenoproteins: An Overview on Dif - reuteri Lb26 DSM16341. Journal of integrated Omics, 2013. ferent Biological Systems. Current Protein and Peptide Science, 2014, 15, 598-607.

Bifidobacterium animalis subsp. lactis - Bb1 (DSM 17850) (under worldwide exclusive license from BIOMAN for nutraceutical and pharma applications) RAW MATERIAL AND FINISHED DOSAGE FORM FUNCTIONALITY Carrier of zinc with High Bioavailability: • Normal function of the immune system • Normal DNA synthesis and cell division • Protection of DNA, proteins and lipids from oxidative damage • Maintenance of normal bone • Normal cognitive function • Fertility and reproduction

SCIENTIFIC SUPPORT In vitro study Mogna L. et al. Selenium and zinc internalized by Lactobacillus buchneri Lb26 (DSM 16341) and Bifidobacterium lactis Bb1 (DSM 17850): im- proved bioavailability using a new biological approach. J Clin Gastroen- terol. 2012; 46 Suppl:S41-5.

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- MB109 (DSM 23731) g Bifidobacterium bifidum + a n - 04 (DSM 23233) a

Bifidobacterium longum m

l

DAILY DOSAGE IN CLINICAL STUDY 1 billion CFU/strain FINISHED DOSAGE FORM o r e t FUNCTIONALITY Cardiovascular health • Cholesterol lowering s e l o

SCIENTIFIC SUPPORT h C

Human clinical trial In vitro and in vivo testing - Guardamagna O. et al. Bifidobacteria supplementation: effects on plasma Bordoni et al. Cholesterol-lowering probiotics: in vitro selection and in lipid profile in dyslipidemic children. Nutrition (2014), doi: 10.1016/ j.nut. vivo testing of Bifidobacteria . Appl. Microbiol. Biotechnol. 2013. m s i

2014.01.014. 97:8273-8281. l o b a t Bifidobacterium breve - MB113 (DSM 23732 ) e m /

Bifidobacterium lactis - MB2409 (DSM 23733) y g o Bifidobacterium bifidum - MB109 (DSM 23731) l o i d

Bifidobacterium bifidum - BB06 (DSM 24688, formerly MB 107) r a

Bifidobacterium animalis subsp. lactis - BS07 (DSM 24690, formerly MB 243) C FINISHED DOSAGE FORM FUNCTIONALITY Cardiovascular health • Cholesterol lowering

SCIENTIFIC SUPPORT In vitro and in vivo testing Bordoni et al. Cholesterol-lowering probiotics: in vitro selection and in vivo testing of Bifidobacteria . Appl. Microbiol. Biotechnol. 2013. 97:8273-8281.

25 t

- BI02 (DSM 24687, formerly MB287) n

Bifidobacterium infantis e

RAW MATERIAL m e

AND FINISHED DOSAGE FORM g FUNCTIONALITY Cardiovascular health • Cholesterol lowering a n

SCIENTIFIC SUPPORT a m

Internal in vitro data on Bile Salt Hydrolase (BSH) production available upon request l o r e t s e l

Limosilactobacillus fermentum - ME-3 (DSM 14241) (formerly Lactobacillus fermentum ) o h C (under license from the University of Tartu for food applications) -

RAW MATERIAL m

AND FINISHED DOSAGE FORM s • • FUNCTIONALITY Cardiovascular health LDL-cholesterol lowering Antioxidant properties i l

SCIENTIFIC SUPPORT o b

Many scientific studies are available, including several human clinical trials a t e m / y g o l o i d r a C

26 e c

Bifidobacterium breve - BR03™ (DSM 16604) n + a m - FP4 (DSM 18616) r

Streptococcus thermophilus o f r

DAILY DOSAGE IN CLINICAL STUDY 1) 5 billion CFU + 5 billion CFU RAW MATERIAL e

AND FINISHED DOSAGE FORM p

s

• t

FUNCTIONALITY Immune response improving Performance enhancing r o

SCIENTIFIC SUPPORT p S

Human clinical trials In vitro studies -

1) Jäger R. et al. Probiotic Streptococcus thermophilus FP4 and Bifido - a) Nicola S. et al. Interaction between probiotics and human immune s c bacterium breve BR03 Supplementation Attenuates Performance and cells: the prospective anti-inflammatory activity of Bifidobacterium breve i t

Range-of-Motion Decrements Following Muscle Damaging Exercise. Nu - BR03. AgroFOOD, 2010; 21(2):S44-47. e trients. 2016 Oct 14;8(10). pii: E642. t b) Mogna L. et al. Assessment of the in vitro inhibitory activity of specific e i 2) Pane M. et al. Gut Microbiota, Probiotics, and Sport: From Clinical Evi - probiotic bacteria against different Escherichia coli strains (LP01, LP02, D dence to Agonistic Performance. J Clin Gastroenterol, 2018;52:S46-S49. LR04, LR06, LPS01, LDD01, BR03, B632). J Clin Gastroenterol. 2012; 46 Suppl:S29-32. + Internal data available upon request on CLA production and protection of gut epithelial barrier with BR03 (TEER)

Bifidobacterium breve - BR03™ (DSM 16604) t n

RAW MATERIAL e

AND FINISHED DOSAGE FORM m •

FUNCTIONALITY Restoration of a better dietary ω-6/ ω-3 balance Conjugated linoleic acids (CLA) production e

• Prospective use in the treatment of obesity g a n

SCIENTIFIC SUPPORT Internal data available upon request a m

t h g i e W

-

s c i t e t e i D

27 t

04 (DSM 23233) n

Bifidobacterium longum - e

DAILY DOSAGE IN CLINICAL STUDY 1 billion CFU FINISHED DOSAGE FORM m e g

FUNCTIONALITY Restoration of a better dietary ω-6/ ω-3 balance • Conjugated linoleic acids (CLA) production a • • n

Prospective use in the treatment of obesity Cholesterol management a m

SCIENTIFIC SUPPORT t h

Human clinical trial g i

Guardamagna O. et al. Bifidobacteria supplementation: effects on pla - e W

sma lipid profile in dyslipidemic children. Nutrition (2014), doi: -

10.1016/j.nut.2014.01.014. s c

Internal data available upon request i t e t e i

Lactobacillus gasseri - LGS06 (DSM 32405) D RAW MATERIAL AND FINISHED DOSAGE FORM FUNCTIONALITY Weight management

SCIENTIFIC SUPPORT Scientific publications are available on gasseri strains on weight loss and reduction of visceral fats

28 a d

Limosilactobacillus fermentum - LF5 (CNCM I-789) (API) (formerly Lactobacillus fermentum ) i d

DAILY DOSAGE IN CLINICAL STUDY 1,2,3,4) 1 billion CFU FINISHED DOSAGE FORM n a C

FUNCTIONALITY Vaginal health • Inhibition of Candida strains • Treatment of vulvovaginal candidiasis (VVC) -

SCIENTIFIC SUPPORT y g

Human clinical trials In vitro studies o 1) Presidio Ospedaliero Delmati, Divisione di Ostetricia - Ginecologia. LF5 a) Deidda F. et al. The In Vitro Effectiveness of Lactobacillus fermentum l o

- LAB: studio di tollerabilità locale e di attività in pazienti affette da Can - Against Different Candida Species Compared With Broadly Used Azoles. c dida albicans . 1992. J Clin Gastroenterol, Vol 50, Supp. 2, November/December 2016. e n

2) Centro di ricerca: USSL Lombardia 55 - Presidio Ospedaliero Delmati, b) Deidda F. et al. In Vitro Activity of Lactobacillus fermentum LF5 Against y

S. Angelo Lodigiano, Divisione di Ostetricia-Ginecologia, Primario: Dott. Different Candida Species and Gardnerella vaginalis A New Perspective G Francesco Rovere. LF5 (lAB): Studio di dose range finding in pazienti af - to Approach Mixed Vaginal Infections? J Clin Gastroenterol Volume 50, fette da Candida albicans . 1992. Supp. 2, November/December 2016. 3) Donini G. Studio clinico sull’efficacia e la tollerabilità di LF5 (LAB) cap - sule vaginali in confronto a placebo in pazienti affette da Candida Albicans . Ospedale S. Salvatore, Divisione Ostetrico-Ginecologica, Pesaro. 1992. 4) Rovere F. Local tolerability and activity study in patients suffering from Candida albicans (“Delmati2 Hospital, Italy, 1992).

Limosilactobacillus fermentum - LF08 (DSM 18297) (formerly Lactobacillus fermentum ) RAW MATERIAL FUNCTIONALITY Inhibition of Candida strains AND FINISHED DOSAGE FORM

SCIENTIFIC SUPPORT: Internal vitro data, available upon request

Limosilactobacillus fermentum - LF09 (DSM 18298) (formerly Lactobacillus fermentum ) FINISHED DOSAGE FORM FUNCTIONALITY Restoration of a physiological gut barrier • Inhibition of Candida growth • Strain from brushing of the gut mucosa

SCIENTIFIC SUPPORT: In vitro data In vitro study Deidda F. et al. The In Vitro Effectiveness of Lactobacillus fermentum Against Different Candida Species Compared With Broadly Used Azoles. J Clin Gastroenterol. 2016 Nov/Dec;50 Suppl 2, S171-S174

29 a

(formerly Lactobacillus fermentum d Limosilactobacillus fermentum - LF10 (DSM 19187) ) i d

DAILY DOSAGE IN CLINICAL STUDY 1,2) 400 million CFU FINISHED DOSAGE FORM n a C

FUNCTIONALITY Vaginal health • Inhibition of Candida strains • Counteraction of vulvovaginal candidiasis (VVC) -

SCIENTIFIC SUPPORT y g

Human clinical trials In vitro study o l

1)Vicariotto F. et al. Effectiveness of the association of 2 probiotic strains Deidda F. et al. In vitro effectiveness of Lactobacillus fermentum against o formulated in a slow release vaginal product, in women affected by vul - different Candida species compared with broadly used azoles. Journal c vovaginal candidiasis: a pilot study. J Clin Gastroenterol. 2012; 46 e

of Clinical Gastroenterology, 2016;50:S171-S174. n

Suppl:S73-80. y

2) Murina F et al. Can Lactobacillus fermentum LF10 and Lactobacillus G acidophilus LA02 in a Slow-release Vaginal Product be Useful for Pre - vention of Recurrent Vulvovaginal Candidiasis? A Clinical Study. J Clin Gastroenterol 2014;48:S102-S105.

Limosilactobacillus fermentum - LF11 (DSM 19188) (formerly Lactobacillus fermentum ) DAILY DOSAGE IN CLINICAL STUDY 800 million CFU FINISHED DOSAGE FORM

FUNCTIONALITY Vaginal health • Inhibition of Candida strains • Counteraction of vulvovaginal candidiasis (VVC)

SCIENTIFIC SUPPORT In vitro data Deidda F. et al. In vitro effectiveness of Lactobacillus fermentum against different Candida species compared with broadly used azoles. Journal of Clinical Gastroenterology, 2016;50:S171-S174.

Limosilactobacillus fermentum - LF16 (DSM 26856) (formerly Lactobacillus fermentum ) FINISHED DOSAGE FORM FUNCTIONALITY Vaginal health • Inhibition of Candida growth

SCIENTIFIC SUPPORT Internal in vitro data, available upon request

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FINISHED DOSAGE FORM n a

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SCIENTIFIC SUPPORT y g

In vitro study c) Tomas MSJ. Et al. Characterization of potentially probiotic vaginal lac - o l

a) Tomas MSJ. Et al. Growth and lactic acid production by vaginal Lac - tobacilli isolated from Argentinean women. British Journal of Biomedical o tobacillus acidophilus CRL 1259, and inhibition of uropathogenic Esche - Science, 2005; 62(4). c richia coli, Journal of Medical Microbiology, 2003;52-1-8. e d) Zàrate G. and Nader-Macias ME. Influence of probiotic vaginal lacto - n b) Ocana V. and Nader-Macias ME. Adhesion of Lactobacillus vaginal bacilli on in vitro adhesion of urogenital pathogens to vaginal epithelial y strains with probiotic properties to vaginal epithelial cells. Biocell, cells. Letters in Applied Microbiology ISSN 0266-8254; G 2001;25(3):265-273;

Lactobacillus acidophilus - CRL1294 (DSM 24513) (under exclusive worldwide license from the CERELA) h

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l a n i g a v

Lactobacillus crispatus - CRL1251 (DSM 24438) -

(under exclusive worldwide license from the CERELA) y g RAW MATERIAL o FUNCTIONALITY Vaginal health AND FINISHED DOSAGE FORM l o c e n y G

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Limosilactobacillus fermentum - LF5 (CNCM I-789) (formerly Lactobacillus fermentum ) s o n

DAILY DOSAGE IN CLINICAL STUDY 1,2,3,4) 1 billion CFU FINISHED DOSAGE FORM i g

• • a

FUNCTIONALITY Vaginal health Inhibition of Candida strains Treatment of vulvovaginal candidiasis (VVC) v

l a

SCIENTIFIC SUPPORT i r e

Human clinical trial In vitro study t Deidda F. et al. In Vitro Activity of Lactobacillus fermentum LF5 Against c For the clinical studies on LF5 in Candida, please refer to the prior a

Different Candida Species and Gardnerella vaginalis : A New Perspective B section on Candida -

to Approach Mixed Vaginal Infections? J Clin Gastroenterol. 2016;

50:S168-S170. y g o l o

Limosilactobacillus fermentum - LF15 (DSM 26955) (formerly Lactobacillus fermentum ) + c e n

Lactiplantibacillus plantarum - LP01™ (LMG P-21021) (formerly Lactobacillus plantarum ) y

DAILY DOSAGE IN CLINICAL STUDY 400 million CFU/strain/tablet + Tara gum + FOS + Arabinogalactan FINISHED DOSAGE FORM G

FUNCTIONALITY Vaginal health • Inhibition of Gardnerella vaginalis • Counteraction of Bacterial Vaginosis (BV)

SCIENTIFIC SUPPORT Human clinical trial Vicariotto F. et al. Effectiveness of the two microorganisms L. fermentum LF15 and L. plantarum LP01, formulated in slow release vaginal tablets, in women affected by Bacterial Vaginosis: a pilot study. J Clin Gastroen - terol. 2014; 48 Suppl:S106-112. Further study available on the anti-pathogen activity of LP01 against E. coli in the anti-pathogen section (gastroenterology).

New Study Lactiplantibacillus plantarum - LP02 (LMG P-21020) (formerly Lactobacillus plantarum ) Limosilactobacillus fermentum - LF10 (DSM 19187) (formerly Lactobacillus fermentum ) DAILY DOSAGE IN CLINICAL STUDY 500 million per strain FINISHED DOSAGE FORM

FUNCTIONALITY Vaginal health • Counteraction of Candida vulvovaginitis • Counteraction of C andida vulvovaginitis including recurrences

SCIENTIFIC SUPPORT Clinical study Murina F. et al. Thymol, eugenol and lactobacilli in a medical device for the treatment of bacterial vaginosis and vulvovaginal candidiasis . New Micro - biologica, 41,3, 220-224, 2018, ISN 1121-7138.

34 1 n n B a ( B S S D B I L M F S F S F I H n n u U U U c i t C C C e 6 A i u c r t

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Gynecology - Pregnancy h t Lactobacillus crispatus - LCR01 (DSM 24619) l a

RAW MATERIAL e h

FUNCTIONALITY Vaginal health • Rebalance of a healthy vaginal microbiota • Inhibition of Candida AND FINISHED DOSAGE FORM l a n SCIENTIFIC SUPPORT i g

L. crispatus is a species naturally predominant in the healthy vaginal ecosystem. A body of literature shows that women with a vaginal ecosystem do - a V minated by L. crispatus are less at risk of bacterial vaginosis, miscarriage, preterm birth and sexually transmissible diseases d n a

y c n

Lactobacillus gasseri - LGS06 (DSM 32405) a n

RAW MATERIAL g e

FUNCTIONALITY Vaginal health • Rebalance of a healthy vaginal microbiota AND FINISHED DOSAGE FORM r P

- SCIENTIFIC SUPPORT y

L. gasseri is a species naturally predominant in the healthy vaginal ecosystem. Literature shows that gasseri is associated with a decreased risk of g

early preterm birth and strains of gasseri have been found to present antagonistic activity against vaginal pathogens such as Candida albicans, o Neisseria gonorrhea and Trichomonas vaginalis l o c e n y G

36

i Lactiplantibacillus plantarum - LP01™ (LMG P-21021) (formerly Lactobacillus plantarum ) t U

-

+ y

Lacticaseibacillus paracasei - LPC09 (DSM 24243) (formerly Lactobacillus paracasei ) g o DAILY DOSAGE IN CLINICAL STUDY 1) LP01 2.5 billion + LPC09 1 billion FINISHED DOSAGE FORM l o r

FUNCTIONALITY Cystitis • Inhibition of E. coli • Metabolization of oxalates, prevention of kidney stones U

SCIENTIFIC SUPPORT Clinical study In vitro studies 1) Vicariotto F. Effectiveness of An Association of a Cranberry Dry a) Mogna L. et al. Assessment of the in vitro inhibitory activity of spe - Extract, D-Mannose, and the 2 Microorganisms Lactobacillus planta - cific probiotic bacteria against different Escherichia coli strains . J Clin rum LP01 and Lactobacillus paracasei LPC09 in Women Affected by Gastroenterol. 2012; 46 Suppl:S29-32. Cystitis. Journal of Clin Gastroenterol 2014;48:S96-S101. b) Mogna L. et al. Screening of different probiotic strains for their in vitro ability to metabolise oxalates: any prospective use in humans? J Clin Gastroenterol. 2014; 48 Suppl:S91-95. + Internal data on anti-inflammatory and anti-oxidant properties avai - lable upon request

Lactiplantibacillus plantarum - LP01™ (LMG P-21021) (formerly Lactobacillus plantarum ) Lactiplantibacillus plantarum - LP02 (LMG P-21020) (formerly Lactobacillus plantarum ) Lacticaseibacillus rhamnosus - LR04 (DSM 16605) (formerly Lactobacillus rhamnosus ) Lacticaseibacillus rhamnosus - LR06 (DSM 21981) (formerly Lactobacillus rhamnosus ) Lactiplantibacillus pentosus - LPS01 (DSM 21980) (formerly Lactobacillus pentosus ) Bifidobacterium breve - BR03™ (DSM 16604) RAW MATERIAL FUNCTIONALITY Cystitis • Inhibition of E. coli AND FINISHED DOSAGE FORM SCIENTIFIC SUPPORT In vitro study Mogna L. et al. Assessment of the in vitro inhibitory activity of specific probiotic + Internal data on anti-inflammatory and anti-oxidant properties available bacteria against different Escherichia coli strains (LP01, LP02, LR04, LR06, upon request for some of these strains LPS01, LDD01, BR03, B632). J Clin Gastroenterol. 2012; 46 Suppl:S29-32.

37 LDD01 (DSM 22106) Lactobacillus delbrueckii subsp. delbrueckii - Uti FINISHED DOSAGE FORM FUNCTIONALITY Inhibition of pathogens E. coli, Klebsiella and gas-producing coliforms

SCIENTIFIC SUPPORT In vitro studies c) Mogna L. et al. In Vitro Inhibition of Klebsiella pneumoniae by Lacto- a) Mogna L. et al. Assessment of the in vitro inhibitory activity of specific bacillus delbrueckii subsp. delbrueckii LDD01 (DSM 22106): An Inno- Urology - - Urology probiotic bacteria against different Escherichia coli strains. J Clin Gastro- vative Strategy to Possibly Counteract Such Infections in Humans? J Clin enterol. 2012; 46 Suppl:S29-32. Gastroenterol. 2016 Nov/Dec;50 Suppl 2, Proceedings from the 8th Pro- b) Savino F. et al. Antagonistic effect of Lactobacillus strains against gas- biotics, Prebiotics & New Foods for Microbiota and Human Health mee- producing coliforms isolated from colicky infants. BMC Microbiology ting held in Rome, Italy on September 13-15, 2015:S136-S139. 2011, 11:157.

Bifidobacterium breve - B632™ (DSM 24706) FINISHED DOSAGE FORM FUNCTIONALITY Inhibition of pathogens E. coli and Enterobacteriaceae

SCIENTIFIC SUPPORT In vitro studies b) Simone M. et al. The Probiotic Bifidobacterium breve B632 Inhibited a) Mogna L. et al. Assessment of the in vitro inhibitory activity of specific the Growth of Enterobacteriaceae within Colicky Infant Microbiota Cultu- probiotic bacteria against different Escherichia coli strains (LP01, LP02, res. BioMed Research International 1-6, 2014. LR04, LR06, LPS01, LDD01, BR03, B632). J Clin Gastroenterol. 2012; 46 Suppl:S29-32.

Ligilactobacillus salivarius - CRL 1328 (DSM 24441) (formerly Lactobacillus salivarius) RAW MATERIAL FUNCTIONALITY Prevention of urogenital infections • Inhibition of Enterococcus faecalis, Enterococcus faecium AND FINISHED DOSAGE FORM and Neisseria gonorrhea • Inhibition of Candida

SCIENTIFIC SUPPORT In vitro studies d) Rovere F. Local tolerability and activity study in patients suffering from a) Ocana V. et al. Characterization of a bacteriocin like substance produced Candida albicans (Delmati2 Hospital, Italy, 1992). by a vaginal Lactobacillus salivarius strain. Applied and Environmental Mi- e) Gillor O. et al. The dual role of bacteriocins as anti- and probiotics. Appl crobiology, 1999; 65(12):5631-5635. Microbiol Biotechnol. 2008 December; 81(4): 591–606. doi: 10.1007/ b) Ocana V. et al. Surface characteristics of lactobacilli isolated from human s00253-008-1726-5. vagina. J. Gen. Appl. Microbiol., 1999; 45:203-212. f) Dover S.E. et al. Natural antimicrobials and their role in vaginal health: a c) Tomas MSJ. et al. Influence of pH, temperature and culture media on short review. Int J Probiotics Prebiotics. 2008 ; 3(4): 219–230. the growth and bacteriocin production by vaginal Lactobacillus salivarius g) Juárez Tomás M.S. et al. Viability of vaginal probiotic lactobacilli during re- CRL 1328. Journal of Applied Microbiology, 2002; 93: 714-724. frigerated and frozen storage. Anaerobe, Vol 10, Issue 1, February 2004, 1-5.

38 t p L S v c 2 V M D a J I C L S ( L B S F F L e n D e o u b a n U U r i t ) C C l - r c i o u o

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Chiancone F, Carrino M, Meccariello C, Pucci L, Fedelini M, Fedelini l o

P. The Use of a Combination of Vaccinium Macracarpon, Lycium bar - r

barum L. and Probiotics (Bifiprost®) for the Prevention of Chronic Bac - U terial Prostatitis: A Double-Blind Randomized Study. Urol Int. 2019; 103(4):423-426. doi: 10.1159/000502765.

Lacticaseibacillus paracasei - LPC09 (DSM 24243) (formerly Lactobacillus paracasei ) Lactobacillus acidophilus - LA02 (DSM 21717) FINISHED DOSAGE FORM Lactiplantibacillus plantarum - LP01™ (LMG P-21021) (formerly Lactobacillus plantarum ) Limosilactobacillus reuteri - LRE02 (DSM 23878) (formerly Lactobacillus reuteri ) Bifidobacterium animalis subsp. lactis - Bb1 (DSM 17850) Bifidobacterium breve - BR03™ (DSM 16604) Bifidobacterium longum - BL03 (DSM 16603) RAW MATERIAL FUNCTIONALITY Oxalate degradation • Reduction of intestinal inflammation • Potential reduction AND FINISHED DOSAGE FORM of kidney stones incidence

SCIENTIFIC SUPPORT In vitro study Mogna L. et al. Screening of different probiotic strains for their in vitro + Internal data on anti-inflammatory and anti-oxidant properties avai - ability to metabolise oxalates: any prospective use in humans? (LPC09, lable upon request on certain strains LA02, LP01, LRE02, BR03, BL03) J Clin Gastroenterol. 2014; 48 Clinical studies on-going on LP01+LPC09+Bb1 and other actives in Suppl:S91-95. prostate health

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• Inhibition of E. coli and Candida n i a

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Marotta A. et al., Effects of Probiotics on Cognitive Reactivity, Mood, Data is available upon request on the preclinical rationale of selection u

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DAILY DOSAGE IN CLINICAL STUDY 1.5 billion CFU + 1.5 billion CFU + 1.5 billion CFU + 500 million CFU FINISHED DOSAGE FORM r O FUNCTIONALITY Restoration of a healthy oral flora • Improvement of the incidence and severity of bad breath (halitosis) • Inhibition of pathogens and Volatile Sulphur Compounds producing bacteria

SCIENTIFIC SUPPORT Human clinical trial In vitro studies Del Piano M. et al. Correlation between specific bacterial groups in the a) Mogna L. et al. In Vitro Inhibition of Klebsiella pneumoniae by Lacto - oral cavity and the severity of halitosis: any possible beneficial role for se - bacillus delbrueckii subsp. delbrueckii LDD01 (DSM 22106). An Inno - lected Lactobacilli? J Gastroint Dig Syst, 2014; 4:197. vative Strategy to Possibly Counteract Such Infections in Humans? J Clin Gastroenterol, Vol 50, Supp. 2, November/December 2016. + Refer to gastroenterology section for further clinical studies on this blend b) Mogna L. et al. Assessment of the in vitro inhibitory activity of specific probiotic bacteria against different Escherichia coli strains (LP01, LP02, LR04, LR06, LPS01, LDD01, BR03, B632). J Clin Gastroenterol. 2012; 46 Suppl:S29-32. + Internal data on immunomodulation, anti-oxidant activity and epithelial barrier effect (TEER in Caco2 cells) available upon request for some of these strains s

Lacticaseibacillus rhamnosus - GG (ATCC 53103) (formerly Lactobacillus rhamnosus ) e i • r DAILY DOSAGE IN CLINICAL STUDY 1) 5 billion CFU (uncoated) 1 billion cells (microencapsulated) RAW MATERIAL a

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Gut-brAIn pag. 43 Probiotics like nobody else OurOur IInnovativennovative orAl CAre pag. 47 Probiotical S.p.A. Via E. Mattei, 3, 28100 Novara (NO), Italy - T: +39 0321 46 59 33 61 Strains:Sttrains:i F: +39 0321 49 26 93 - email: [email protected] - www.probiotical.com teChnoloGIeS pag. 49 ReadyReaddy fforor YourYour HealthHeallth