Piglet post-weaning diarrhoea without pharmacological zinc oxide and colistin — live oral E. coli vaccine, fermented liquid feed, probiotics and low-protein diets

Replaces: medicinal zinc oxide and colistin in weaner diets · Species: pigs · Evidence: high

The chemical problem#

• Zinc oxide at 2,500–3,000 ppm (about 20–30 times the nutritional requirement) was used for decades against post-weaning diarrhoea (PWD). About 90 % passes into manure, and zinc accumulates in soils and harms soil life and aquatic ecosystems. High zinc co-selects for antibiotic resistance (e.g. livestock-associated MRSA, zinc-resistance gene czrC). The EU withdrew all veterinary ZnO products from June 2022.
• Colistin in piglets is a major driver of mcr-1 resistance (see V01). The EMA recommended drastic reductions.
• PWD is caused mainly by enterotoxigenic E. coli (ETEC) with F4 (K88) and F18 fimbriae, triggered by weaning stress, low feed intake and a high-protein diet.

Product overview#

A combined program has replaced ZnO in Denmark, the Netherlands and other EU countries:

1. Live oral bivalent E. coli F4/F18 vaccine (e.g. Coliprotec F4/F18, authorized in the EU): one oral dose from 18 days of age induces local (gut) immunity before weaning.
2. Fermented liquid feed (FLF): feed fermented with lactic acid bacteria (pH below 4.5, high lactic acid) inhibits E. coli and Salmonella in the feed and in the gut.
3. Probiotics (Bacillus spp., Lactobacillus, Enterococcus faecium, Saccharomyces yeast) and functional fibres (e.g. sugar-beet pulp, wheat bran).
4. Nutrition: lower crude protein (about 16–18 %) with essential amino acids, lower acid-binding capacity, highly digestible protein sources, plus organic acids (formic, lactic, benzoic).
5. Management: later weaning (at 28 days or more), creep feeding, small groups, temperature, water quality.

Active ingredient / Composition#

• Vaccine: live non-pathogenic E. coli strains expressing F4 and F18 fimbriae (composition per SmPC).
• FLF: Lactobacillus plantarum/Pediococcus starter cultures, fermented 24–48 h.
• Probiotics per EU feed additive authorization.

Key facts#

Advantages#

• Removes ZnO emissions (about 1–2 kg Zn/t of feed) from agriculture.
• Reduces antibiotic use in weaners, the age group with the highest antibiotic use in pigs.
• FLF also improves feed intake and gut morphology.
• No resistance selection from the vaccine or fermentation.

Mode of action#

• Vaccine: oral live antigens stimulate secretory IgA against F4/F18 fimbriae, which blocks ETEC adhesion to the gut wall.
• FLF/organic acids: low pH and lactic acid inhibit Enterobacteriaceae in the feed and stomach.
• Low protein: less undigested protein reaches the colon, so less putrefactive fermentation and fewer ETEC proliferate.
• Probiotics/fibre: competitive exclusion and butyrate production (gut barrier).

Application#

Limitations#

• The vaccine only covers F4/F18 ETEC, so diagnosis (PCR of fimbriae types) is needed.
• Farms with poor hygiene or early weaning will still see problems; management must change too.
• FLF needs investment and good hygiene (otherwise yeast or mould spoilage).

Evidence of displacement — D1: works, adoption not proven#

Assessment (hand-reviewed): No national figure after the June 2022 EU ban: 81% of Danish herds still used ZnO in 2018; a 14-farm survey is too small.

Figures found (verified as quoted, but the assessment above explains why they do not count as displacement evidence for this substitution):

• displacement — By 2018, 81% of Danish pig herds were using pharmaceutical zinc oxide (pZnO). (Denmark, 2018; peer-reviewed: exa.ai)
• displacement — In a survey of producers, 57% reported that weaner pigs were not fed a diet containing zinc oxide, while 36% were still feeding a diet containing zinc oxide. (United Kingdom, 2026; peer-reviewed: frontiersin.org)
• driver — The European Union banned the use of medicinal levels of zinc oxide (2,500–3,000 ppm) in piglet feed, effective June 2022, due to environmental concerns and the promotion of antibiotic resistance. (European Union, 2022; peer-reviewed: porcinehealthmanagement.biomedcentral.com)
• performance — No single alternative practice has been identified that is as effective and inexpensive as the use of 2,500 ppm zinc oxide for treating post-weaning diarrhoea. (—, 2023; weak: pure.sruc.ac.uk)

Suppliers — real products and services (from the vendor index)#

Honest finding: the vendor index has no dedicated zinc-oxide replacement product. This is recorded as a supplier gap — the companies below are the closest capabilities.

Companies below are active vendors in the vendor index whose own card (profile / official website) shows this product or service — matched 2026-09-28 by keyword and checked by hand against the card text. Being listed is not an endorsement; open each card for evidence, contacts and status.

Government funding signals#

Public grants for a specific technology are a leading indicator: governments fund what regulators want to replace and what is close to practical adoption. Searched on 2026-09-27 in: EU CORDIS (FP7, Horizon 2020, Horizon Europe), US federal awards (USAspending: USDA NIFA/ARS/APHIS/Forest Service, EPA, DOE, NOAA, USAID; plus NSF and NIH), UK UKRI Gateway to Research, Australian Research Council. Each grant below was reviewed by hand for relevance. China, Brazil and India are covered in the subsection below (publication-acknowledged grants). Not covered: Russia (RSF, FASIE — not reachable from the research environment) and national agencies outside these databases. Amounts are the funder’s contribution as recorded (US NIH/UKRI: per award or fiscal year).

Signal: Strong. 4 relevant grant(s) · about €1.9M in total · jurisdictions: Australia, UK, USA.

China, Brazil, India — national research grants acknowledged in publications#

Chinese, Brazilian and Indian funders have no open grant databases reachable here, so this measures scientific papers published since 2015 that acknowledge national government grants, taken from the grant numbers publishers deposit with Crossref. Only papers whose title contains this article’s key terms are counted (a conservative lower bound; “100+” = search window full). It shows research-funding intensity, not budgets. Funders: China — NSFC, National Key R&D Program, China Agriculture Research System; Brazil — CNPq, CAPES, FAPESP, Embrapa, FAPEMIG; India — DBT, DST, ICAR, SERB, CSIR, BIRAC. Rating per country: Strong ≥50 papers · Moderate 10–49 · Weak 1–9.

Scientific evidence#

• Fairbrother JM, Nadeau É, Gyles CL (2005). Escherichia coli in postweaning diarrhea in pigs: an update on bacterial types, pathogenesis, and prevention strategies. Animal Health Research Reviews 6: 17–39.
• Heo JM, Opapeju FO, Pluske JR, Kim JC, Hampson DJ, Nyachoti CM (2013). Gastrointestinal health and function in weaned pigs: a review of feeding strategies to control post-weaning diarrhoea without using in-feed antimicrobial compounds. Journal of Animal Physiology and Animal Nutrition 97: 207–237.
• Nadeau É, Fairbrother JM, Zentek J, et al. (2017). Efficacy of a single oral dose of a live bivalent E. coli vaccine against post-weaning diarrhea due to F4 and F18-positive enterotoxigenic E. coli. The Veterinary Journal 226: 32–39.
• Missotten JAM, Michiels J, Degroote J, De Smet S (2015). Fermented liquid feed for pigs: an ancient technique for the future. Journal of Animal Science and Biotechnology 6: 4.
• European Commission Implementing Decision C(2017) 4529 — withdrawal of marketing authorisations for veterinary medicinal products containing zinc oxide for oral use in food-producing species (effective June 2022).

Bioeconomy value#

Fermentation, living vaccines and microbial additives replace a mined heavy metal and a critical antibiotic. Manure becomes safer to recycle as fertilizer.