VetPlus Promax Paste 18ml

FOR ANIMAL USE ONLY — Administer as directed by a veterinarian or as per the VetPlus label instructions. VetPlus Promax Paste is a veterinary nutraceutical probiotic and gut health supplement — not a veterinary medicine. Promax Paste is indicated for supportive management of acute diarrhoea, post-antibiotic gut dysbiosis, and intestinal microbiome disruption in dogs. It is not a substitute for veterinary diagnosis or treatment of diarrhoea — dogs with persistent (>48 hours), bloody, or severe diarrhoea, or diarrhoea accompanied by vomiting, lethargy, anorexia, or systemic illness signs require prompt veterinary assessment to rule out parvovirus, haemorrhagic gastroenteritis (HGE), intussusception, foreign body obstruction, toxin ingestion, or other conditions requiring specific veterinary treatment. Keep out of reach of children. Store in a cool, dry place; use within the period stated on the packaging after opening.

VetPlus Promax Paste 18ml Medium Breed | Probiotic, Prebiotic, Kaolin & Pectin Gut Health Paste | Digestive Support, Diarrhoea Relief & Intestinal Balance for Dogs

VetPlus Promax Paste is a veterinary nutraceutical probiotic, prebiotic, and gut protectant paste manufactured by VetPlus Ltd (UK), formulated for the supportive management of acute diarrhoea, post-antibiotic gut dysbiosis, dietary indiscretion-associated GI upset, and intestinal microbiome disruption in dogs. Promax Paste contains four complementary active components: Enterococcus faecium DSM 10663/NCIMB 10415 (the SF68 strain) — the only probiotic strain with formal EFSA FEEDAP Panel regulatory approval for dogs as a zootechnical feed additive for intestinal flora stabilisation; fructooligosaccharides (FOS) — the short-chain prebiotic fibre that selectively feeds Lactobacillus and Bifidobacterium species in the canine colon; kaolin — the hydrated aluminium phyllosilicate clay mineral with potent intestinal adsorbent, enterotoxin-binding, and mucosal cytoprotective properties; and pectin — the soluble plant cell wall polysaccharide that forms a gel matrix in the GI tract, acting as a protective mucoadhesive layer, a prebiotic fermentation substrate, and a bulking agent for stool normalisation. The 18ml paste volume is sized for medium breed dogs (approximate body weight 10–25 kg). Separate pack sizes are available for small breeds (9ml) and large breeds (30ml).

The Canine Gut Microbiome and the Pathophysiology of Dysbiosis and Acute Diarrhoea

• The canine intestinal microbiome — composition, function, and vulnerability: the healthy canine gastrointestinal tract harbours a complex microbiome: the small intestinal microbiome (duodenum, jejunum, ileum) is relatively sparse (10⁴–10⁸ bacteria/ml luminal contents) and dominated by aerobes and facultative anaerobes (Lactobacillus, Streptococcus, Enterococcus, Clostridium [non-toxigenic species]); the large intestinal microbiome (caecum and colon) is dense (10¹⁰–10¹¹ bacteria/g luminal contents) and dominated by obligate anaerobes (Bacteroidetes [Bacteroides, Prevotella] and Firmicutes [Lachnospiraceae, Ruminococcaceae, Faecalibacterium] — the two dominant phyla constituting >90% of the healthy canine colonic microbiome; Fusobacteria and Proteobacteria are also present in lower proportions); the canine gut microbiome functions: (a) colonisation resistance against intestinal pathogens (competitive exclusion: commensal bacteria compete for mucosal attachment sites, limiting adhesion of enteropathogens [Salmonella, Campylobacter, Clostridium perfringens toxinotype A/C, Clostridium difficile] to the intestinal epithelium; direct antimicrobial production: bacteriocins [Lactobacillus-produced class IIa bacteriocins: pediocin PA-1, enterocin A, nisin — target Gram-positive pathogens including C. perfringens and Listeria monocytogenes] and hydrogen peroxide [produced by Lactobacillus via pyruvate oxidase] are direct bactericidal agents against commensal pathogens; indirect immune exclusion: short-chain fatty acids [SCFAs — acetate, propionate, butyrate — the fermentation products of colonic Firmicutes] acidify the colonic lumen [pH approximately 6.0–6.5] → inhibit the growth of acid-sensitive pathogens); (b) SCFA production: butyrate (the primary energy source for colonocytes [the colonic epithelial cells]: colonocytes derive approximately 60–70% of their ATP from butyrate β-oxidation [butyrate → butyryl-CoA → β-oxidation → acetyl-CoA → TCA cycle]; butyrate also activates GPR41/GPR43 [SCFA G-protein coupled receptors] on colonocytes and enteroendocrine cells → PYY [peptide YY] and GLP-1 release → reduced GI motility and increased absorption time); propionate (gluconeogenic substrate — propionyl-CoA → succinyl-CoA [via methylmalonyl-CoA mutase] → TCA cycle → oxaloacetate → gluconeogenesis in hepatocytes); acetate (the predominant plasma SCFA — peripheral tissue oxidative substrate and lipogenic precursor); (c) intestinal barrier integrity: colonic bacteria regulate tight junction (TJ) protein expression — butyrate via HDAC inhibition (butyrate is a potent Class I and Class IIa HDAC [histone deacetylase] inhibitor → histone H3/H4 hyperacetylation at the promoters of claudin-3, occludin, and ZO-1 genes → increased TJ protein expression → reduced paracellular permeability); Lactobacillus-derived D-amino acids (D-Ala, D-Phe, D-Tyr) activate TLR2 on intestinal epithelial cells (IECs) → NF-κB-dependent claudin-1 upregulation; (d) immune system education and regulation: the gut-associated lymphoid tissue (GALT) — Peyer’s patches (PP), isolated lymphoid follicles (ILFs), and the lamina propria — is the largest lymphoid organ in the dog; commensal bacteria train the mucosal immune system to tolerate harmless antigens while maintaining vigilance against pathogens: dendritic cells (DCs) in the lamina propria sample luminal bacteria via transepithelial dendrites that penetrate tight junctions to directly survey the lumen without disrupting the epithelial barrier → commensal bacterium-educated DCs promote Treg differentiation (via IL-10 and TGF-β production) → oral tolerance to food antigens and commensal bacteria; conversely, pathogen-activated DCs promote Th1/Th17 responses → mucosal defence
• Dysbiosis — the disruption of the microbiome equilibrium and its consequences in dogs: dysbiosis (Greek: dys = bad/altered + biosis = life — an imbalanced microbial community) in dogs occurs when the normal microbiome composition and function is disrupted by: (a) antibiotic exposure: antibiotics are the most common cause of iatrogenic gut dysbiosis in dogs; broad-spectrum antibiotics (amoxicillin-clavulanate, metronidazole, enrofloxacin, tylosin) indiscriminately kill commensal bacteria alongside pathogens; metronidazole (the most commonly prescribed antibiotic for canine diarrhoea) paradoxically causes gut dysbiosis — it preferentially kills strict anaerobes (the Firmicutes and Fusobacteria that produce butyrate) → reduced butyrate production → colonocyte energy deficit → increased intestinal permeability; metronidazole also reduces Lactobacillus and Bifidobacterium (the primary commensal probiotic species) → loss of colonisation resistance → Clostridiodes difficile overgrowth risk; post-antibiotic dysbiosis may persist for weeks to months − canine microbiome recovery after a 2-week amoxicillin-clavulanate course takes approximately 4 weeks for partial recovery and >8 weeks for near-complete recovery (based on 16S rRNA sequencing studies); (b) dietary change/indiscretion: abrupt dietary change (the most common trigger for acute self-limiting diarrhoea in dogs) disrupts the microbiome because the colonic microbial community is adapted to the substrate profile of the habitual diet − a sudden change in carbohydrate type (switching from rice-based to wheat-based), protein source (switching from chicken to beef), or fat content alters the available fermentation substrate → different bacterial species are favoured → temporary dysbiosis until the microbiome adapts; dietary indiscretion (garbage eating, scavenging, eating decomposed food) introduces a sudden high load of non-habitual substrates and potential toxins → osmotic diarrhoea (non-absorbed osmotically active carbohydrates and amino acids in the colon → water retention in the lumen → osmotic diarrhoea) and/or secretory diarrhoea (bacterial toxins from ingested spoiled food activate adenylate cyclase in enterocytes → increased cAMP → PKA phosphorylation of the CFTR chloride channel → Cl− secretion into the lumen → Na+/water follow → secretory diarrhoea); (c) stress: psychological stress (kennelling, travel, rehoming, changes in household routine) activates the HPA axis (hypothalamic-pituitary-adrenal) → cortisol → mast cell degranulation in the intestinal wall → histamine and substance P release → increased intestinal permeability and altered GI motility; the enteric nervous system (ENS — the ‘second brain’; approximately 500 million neurons in the canine GI tract − comparable in neuron number to the spinal cord) is directly regulated by the gut microbiome via the microbiota-gut-brain axis (MGBA: SCFAs activate ENS afferent neurons → vagal afferent signalling → brainstem and hypothalamic modulation of GI motility and secretion; dysbiosis → altered SCFA profile → altered ENS signalling → stress-induced diarrhoea); (d) parvoviral and other enteric infections: viral enteritis (canine parvovirus type 2 [CPV-2] — the single-stranded non-enveloped DNA virus that targets actively dividing intestinal crypt epithelial cells via the transferrin receptor 1 [TfR1; CD71] as its primary receptor; CPV-2 → crypt cell necrosis → villus blunting → malabsorption and bloody diarrhoea − parvoviral enteritis is a veterinary emergency requiring hospitalisation, IV fluid therapy, anti-emetics, and antibiotics for secondary bacterial translocation prophylaxis; Promax Paste is NOT appropriate as the primary treatment for suspected parvovirus and must not delay emergency veterinary care) causes profound dysbiosis as crypt cell necrosis eliminates the rapidly dividing epithelial cells that maintain the mucous layer and tight junction barrier → bacterial translocation

Active Ingredients & Mechanisms of Action

• Enterococcus faecium DSM 10663/NCIMB 10415 (SF68 strain) — the EFSA-approved veterinary probiotic: Enterococcus faecium SF68 is the most extensively researched veterinary probiotic strain in companion animal medicine: (a) regulatory status: E. faecium NCIMB 10415 (SF68) is the only probiotic microorganism with formal European Food Safety Authority (EFSA) FEEDAP Panel scientific opinion approving its use as a zootechnical feed additive (functional group: ‘gut flora stabilisers’) for dogs under EU Regulation 1831/2003 (Commission Regulation [EC] No 1451/2006 and subsequent renewals); the EFSA FEEDAP assessment confirmed: (i) safety for the target species (E. faecium SF68 does not possess transferable vancomycin resistance determinants [vanA/vanB glycopeptide resistance genes] — this is a critical safety distinction: wild-type E. faecium is intrinsically resistant to vancomycin at low levels [vanC1/C2 chromosomal resistance], which is strain-specific and non-transferable; SF68 has been tested and confirmed negative for acquired vanA/vanB resistance plasmids); (ii) safety for the consumer; (iii) safety for the environment; and (iv) efficacy for gut flora stabilisation in dogs and cats; (b) probiotic mechanisms: (i) colonisation resistance via competitive exclusion: E. faecium SF68, when delivered in high CFU counts (VetPlus Promax Paste delivers a high guaranteed CFU count — check label for current CFU specification), transiently colonises the canine small intestine → competes with pathogenic bacteria (Clostridium perfringens, Campylobacter jejuni, Salmonella enterica) for the same mucosal adhesion receptors (fibronectin-binding proteins [FBPs] on the enterocyte surface are adhesion sites for Lactobacillus/Enterococcus surface-layer proteins [S-proteins] and for pathogen adhesins; competitive occupancy of FBPs by SF68 → reduced pathogen adhesion); (ii) bacteriocin production: E. faecium SF68 produces enterocin L50 (EntL50A/EntL50B — a two-peptide class IIb bacteriocin; the synergistic combination of EntL50A [MGAIAKLVAKFGWPIVEAYKQFVKGWRNAIAS] and EntL50B disrupts the cytoplasmic membrane of Gram-positive pathogens [Clostridium perfringens, Listeria monocytogenes, Bacillus subtilis] by forming membrane pores via electrostatic interaction with the negatively charged phospholipid head groups of the target membrane → K+/ATP leakage → membrane depolarisation → target cell death without harming the host enterocyte [mammalian cell membranes have cholesterol that stabilises the membrane against bacteriocin-mediated disruption]); (iii) immune modulation: E. faecium SF68 cell wall components (lipoteichoic acid [LTA] and peptidoglycan fragments [muramyl dipeptide, MDP]) are recognised by TLR2 (LTA) and NOD2 (MDP) pattern recognition receptors (PRRs) on lamina propria DCs → controlled, non-inflammatory NF-κB activation → IL-10 and TGF-β production → Treg expansion → mucosal immune tolerance (the distinction between probiotic-induced and pathogen-induced TLR2 signalling: probiotics deliver LTA in a context of an intact epithelial barrier and low overall PAMPs [pathogen-associated molecular patterns] load → tolerogenic DC activation; pathogens breach the epithelial barrier and deliver high-concentration PAMP signals → pro-inflammatory DC activation); (iv) IgA enhancement: E. faecium SF68 promotes intestinal IgA secretion by plasma cells in the lamina propria (sIgA [secretory IgA] — the dimeric IgA bound to the secretory component [SC; polymeric immunoglobulin receptor [pIgR] ectodomain, cleaved upon transcytosis across the IEC] − is the primary immunoglobulin of intestinal mucosal immunity; sIgA coats luminal bacteria [immune exclusion] and neutralises enterotoxins without activating complement or causing inflammation [the ‘quiet’ mucosal antibody]); (v) butyrate-mediated TJ regulation: E. faecium SF68, as a member of the Firmicutes phylum (lactic acid bacteria − LAB), produces lactic acid and acetic acid as primary fermentation end-products; lactic acid is cross-fed by colonic Roseburia and Coprococcus species (acetate + lactate → butyrate via the Roseburia/Coprococcus butyryl-CoA transferase pathway) → indirect butyrate production → HDAC inhibition → TJ protein upregulation → barrier repair
• Fructooligosaccharides (FOS) — the selective prebiotic fibre: FOS (fructooligosaccharides; short-chain fructans: 1-kestose [GF2], nystose [GF3], and fructosylnystose [GF4]; produced by sucrose transfructosylation [via fungal fructosyltransferase — Aspergillus niger or Aureobasidium pullulans ftf gene products] or by partial inulin hydrolysis [from chicory Cichorium intybus root, a rich source of inulin [GFn, n = 2–60 fructose units]]); FOS are resistant to host digestion: dogs (like all mammals) lack the specific glycoside hydrolases (sucrase-isomaltase [SI/MGAM — Maltase-glucoamylase] can partially hydrolyse sucrose and the β1,2 glycosidic bond of kestose at very low efficiency; inulinase [EC 3.2.1.7] — the enzyme that efficiently cleaves β2,1 fructosyl-fructose bonds — is not expressed in mammalian small intestinal brush border) to digest FOS in the small intestine → FOS reach the colon intact; in the colon: FOS are selectively fermented by Bifidobacterium (via Bifidobacterium-specific inulin-type fructan utilisation [IFU] gene clusters: bfrA/bfrB [Bifidobacterium fructan β-fructosidase] and the BL1656 ABC transporter for FOS import into the cell − a privileged import-first mechanism that allows Bifidobacterium to access FOS before other bacteria can hydrolyse them extracellularly) and Lactobacillus (via intracellular β-fructosidase after SusBCD-like outer membrane transporter-mediated import); this selective fermentation pattern (bifidogenic effect) → increased Bifidobacterium and Lactobacillus relative abundance → increased acetate and lactate production → colonic acidification → growth inhibition of acid-sensitive pathogens (Clostridium perfringens, Salmonella, Shigella); FOS dose-dependently increase faecal Bifidobacterium counts and improve faecal consistency scores (Bristol Stool Scale equivalent in dogs) in multiple canine intervention studies; FOS synbiotic effect with E. faecium SF68: the probiotic bacterium (SF68) is the biotic agent; the FOS (prebiotic) is the selectively fermentable substrate that feeds and amplifies the probiotic’s colonic persistence and activity (the synbiotic combination synergistically improves microbiome restoration vs either component alone)
• Kaolin — the intestinal adsorbent and cytoprotective clay mineral: kaolin (hydrated aluminium silicate; Al₂Si₂O₅(OH)₄; triclinic phyllosilicate mineral; specific surface area approximately 5–25 m²/g depending on particle size [ultrafine kaolin: >20 m²/g; standard kaolin: 5–10 m²/g]; the high surface area provides the adsorptive capacity) is a pharmacologically active intestinal adsorbent: (a) toxin and enteropathogen adsorption: kaolin’s layered aluminosilicate crystal structure (stacked 1:1 tetrahedral Si-O₂ – octahedral Al-OH layers, charge-neutral at the basal faces but with edge hydroxyl groups that carry variable charge [positive at low pH: AlOH2+; negative at high pH: AlO−]) binds: bacterial enterotoxins (Clostridium perfringens alpha-toxin [a zinc metalloenzyme phospholipase C — Zn2+ chelation by kaolin’s edge silanol/aluminol groups reduces C. perfringens alpha-toxin activity]; E. coli heat-labile toxin [LT] and heat-stable toxin [STa: STa is a 19-amino acid peptide that activates guanylate cyclase C [GC-C] → cGMP → CFTR activation → Cl− secretion → secretory diarrhoea; kaolin adsorbs STa via electrostatic interaction between STa’s basic residues and kaolin’s negatively charged silanol groups]); rotavirus (the double-stranded RNA virus that causes acute self-limiting diarrhoea in puppies via the VP8* lectin-like domain binding to sialic acid on enterocyte brush border − kaolin’s silanol surface-hydroxyl groups can competitively adsorb sialylated rotavirus VP8* to the clay surface via hydrogen bonding, reducing viral attachment to the enterocyte sialic acid receptors); (b) mucosal cytoprotection: kaolin forms a physical barrier on the intestinal mucosal surface (kaolin particles, due to their plate-like crystal morphology and moderate mucoadhesion, deposit on the intestinal mucus layer → mechanical protection against enteropathogen adhesion and enterotoxin access to the brush border; this is analogous to the mechanism of smectite [diosmectite] which has a much higher negative surface charge density than kaolin and is the most clinically studied mineral adsorbent in small animal practice); (c) fluid and electrolyte adsorption from the lumen: kaolin’s high specific surface area non-specifically adsorbs water and electrolytes from the intestinal lumen → increased luminal viscosity → slowed intestinal transit → improved absorption time for water and electrolytes; this contributes to the stool-firming effect of kaolin-containing preparations
• Pectin — the soluble fibre, gel former, and prebiotic: pectin (from the Greek pektikos: congealed; a heteropolysaccharide of the plant cell wall; primary composition: homogalacturonan [HG: a linear polymer of α-1,4-linked D-galacturonic acid (GalA) residues, partially methyl-esterified at the C-6 carboxyl group − degree of methyl esterification [DM] determines pectin’s gelling properties: high-methoxyl [HM] pectin [DM >50%]: gels in high-sugar/low-pH conditions; low-methoxyl [LM] pectin [DM <50%]: gels in the presence of Ca2+ [Ca2+–carboxylate cross-linking of adjacent HG chains via the ‘egg-box’ junction zone model]]; rhamnogalacturonan I [RGI: the branched ‘hairy region’ with α-1,4-linked alternating GalA and rhamnose units, decorated with arabinan, galactan, and arabinogalactan I side chains] and rhamnogalacturonan II [RGII: a structurally conserved pectic polysaccharide that forms borate diester cross-links between adjacent pectin chains]); pectin functions in Promax Paste: (a) gel formation and protective mucoadhesive coating: pectin, in the aqueous environment of the intestinal lumen, forms a viscous gel matrix (LM pectin + luminal Ca2+ → ‘egg-box’ junction zones → pectin gel network); the gel coats the intestinal mucosal surface → protective mucoadhesive layer that physically barriers the mucosa from luminal toxins, acid, and pathogens (mucoadhesion: pectin’s carboxylate groups [GalA-COOH] form hydrogen bonds and ionic interactions with the mucin glycoprotein (primarily MUC2 — the secreted gel-forming mucin of the intestinal mucus layer; MUC2 has a tandem repeat core protein with O-linked oligosaccharide chains [core-1 and core-2 O-glycans] that provide multiple hydrogen-bonding acceptor sites for pectin carboxylate groups]); (b) stool normalisation and transit time regulation: pectin’s gel-forming properties increase the viscosity of intestinal contents → slowed intestinal transit → increased fluid/electrolyte absorption time; pectin also acts as a bulking agent for loose stools (the gel network retains water in a structured matrix → water is held within the gel rather than expelled into the lumen → firmer, more formed stools); (c) prebiotic fermentation substrate: pectin reaches the colon largely intact (pectin is not digested by mammalian polygalacturonase, which dogs lack [dogs express no intestinal pectinase activity]; colonic bacteria express pectate lyase [PelA–PelE], rhamnogalacturonate lyase [RglA/RglB], and GalA epimerase for pectin depolymerisation); colonic fermentation of pectin produces SCFAs (primarily propionate and butyrate from HG fermentation; acetate from RGI side chain fermentation) → colonocyte energy support and TJ barrier repair; Bacteroides thetaiotaomicron is a major pectin-fermenting commensal in the canine colon (BtPL1 pectate lyase and BtGH105 unsaturated GalA hydrolase); (d) diarrhoea-associated fluid loss mitigation: the gel matrix formed by pectin in the lumen binds free luminal water → reduced fluid loss from hypersecretory or osmotic diarrhoea → complementary to kaolin’s direct adsorptive mechanism

Indications

• Acute self-limiting diarrhoea in medium breed dogs (dietary indiscretion, dietary change, mild infectious gastroenteritis)
• Post-antibiotic gut dysbiosis — microbiome restoration following antibiotic therapy (metronidazole, amoxicillin-clavulanate, enrofloxacin, tylosin)
• Stress-induced diarrhoea (kennelling, travel, rehoming, environmental change)
• Pre- and post-operative gut microbiome support (surgical procedures with peri-operative antibiotic use)
• Supportive care during intestinal infectious diarrhoea (under veterinary supervision)
• Routine microbiome maintenance during high-risk periods (vaccination, dietary transition)

Directions for Use

• Administer as directed by a veterinarian or as per VetPlus label instructions; dose is body-weight-dependent
• The 18ml pack is sized for medium breed dogs (approximately 10–25 kg body weight); confirm dose with your veterinarian
• Administer orally — directly into the mouth or mixed into food
• For acute diarrhoea: administer at the onset of diarrhoea and continue for a minimum of 5–7 days or as directed; for post-antibiotic use: begin administration at the start of antibiotic therapy and continue for a minimum of 7 days after completing the antibiotic course
• Store in a cool, dry place; use within the period stated on the packaging after opening

Safety Information

• For use in dogs — keep out of reach of children
• Not a substitute for veterinary diagnosis and treatment of severe, bloody, or persistent diarrhoea
• Seek immediate veterinary attention for diarrhoea with blood, profuse watery diarrhoea, vomiting, lethargy, or systemic illness signs
• Use under veterinary supervision in dogs with known gastrointestinal disease or immunocompromise
• Store in a cool, dry place; discard if the paste changes colour, odour, or consistency after opening