**1. Introduction**

294 Antimicrobial Agents

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In recent decades, acidifiers have emerged as viable alternatives to antibiotics in swine diets, in order to stimulate optimal growth performance and prevent various enteric diseases. Antimicrobials have been used for more than 50 years to enhance growth performance and prevent various pig diseases (Gustafson & Bowen, 1997). There is growing public awareness of the relationship between the feed medication with antimicrobials as growth promoters in livestock diets and the risk of developing cross-resistance of pathogens to antibiotics, threatening animals and human health (Corpet, 1996; Mathew et al. 2007; Hunter et al. 2010). During the last few years, as the use of antibiotics in pig diets has decreased, the use of acidifiers has increased.

Acidifiers can be in organic or inorganic acids or associated salts. As a group of chemicals, organic acids are considered to be any organic carboxylic acid of the general structure R-COOH (including fatty acids and amino acids) (Partanen & Mroz, 1999). Organic acids are widely distributed in plants and animals. They are also produced by microbial fermentation of carbohydrates and other fermentable material, predominantly in the large intestine of pigs. Table 1 shows the common name, chemical name, formula and first pKa- the pH at which the acid is half dissociated - of organic acids that are commonly used as dietary acidifiers in pigs (Partanen & Mroz, 1999).

The activity of most common acids, as well as their beneficial effects is shown in Table 2. Acidifiers have received much attention in pig production due to their beneficial effects on growth performance of pigs (Mahan et al. 1996; Partanen, 2001; Papatsiros et al. 2011). Many acids are available as sodium, potassium or calcium salts and several researchers have proposed their use because of their convenient application and their better effects than those of pure state acids. Table 3 shows a list of the most common salts of acids and their properties. The advantage of salts over free acids is that they are generally odourless and easier to handle in the feed manufacturing process due to their solid and less volatile form. Salts of acids are also less corrosive and may be more soluble in water than free acids (Partanen & Mroz, 1999). Although beneficial effects have been reported from trials using supplements of salts in pig diets (Table 3), other studies have not introduced any positive effects (Biagi et al. 2007; Weber & Kerr, 2008).

The Prophylactic Use of Acidifiers as Antibacterial Agents in Swine 297

Inorganic acids added to the pig diets are hydrochloric, sulfuric, and phosphoric acid. Organic and inorganic acids or/and salt form combinations are often used in commercially available acidifiers. The response to mixed acids is generally better than to single acids possibly due to dissociation properties of these acids at various locations in the pig's digestive tract (Hardy

2002; Franco et al. 2005; Partanen et al. 2007; Kasprowicz-Potocka et al. 2009).

Table 2. Activity of most common acids - Beneficial effects

Benefits from the use of dietary acidifiers include positive effects on growth performance and health status (Figure 1). Proposed mechanisms of action include reduction or stabilization of gastric pH, resulting in increased activity of proteolytic enzymes and gastric retention time, and thus led to improvement of protein digestion. Organic acids may influence mucosal morphology or induce alterations in gut microflora through bacteriostatic or bactericidal actions, as well as enhance endogenous enzyme activity, stimulate pancreatic secretions, and they also serve as substrates in intermediary metabolism (Partanen & Mroz, 1999. It is also

**2. Mechanisms of action** 


Table 1. List of acids and their properties

proportions

proportions

proportions

proportions

soluble

soluble

proportions

3.13 very soluble Solid

COOH 4.82 soluble in all

COOH 3.83 very soluble

CHCOOH 4.76 sparingly

COOH 3.02 sparingly

(OH)COOH 3.40 soluble in all

**water Physical form Odour / Taste Production** 

Pungent odour Emission of strong odors

Pungent odour Sour taste

Pungent odour Emission of very strong smells

Rancind, upleasant odour Acrid taste, with a sweetish after taste (similar to ether)

Rancind, disagreeable odour Sour milk taste

Distinctive odour Midly acrid and sour taste

Odourless Tart flavour, fruit-like taste

Odourless Apple taste

taste

Odourless Pleasant sour taste

Highly fragrant odour

**Synthetically:** from methyl formate and formamide, byproduct of acetic acid production and by laboratory

**Naturally:** in many fruits (apples, strawberries and raspberries), honey and nettles

**Synthetically:** by various

**Synthetically:** from ethyl alcohol and carbon monoxide **Naturally:** by bacteria of genus Propionibacterium, as the end product of their fermentation of dietary fibre in the colon

**Synthetically:** by fermentation of sugar or starch **Naturally:** by bacterial fermentation dietary fibre in

**Synthetically:** from chemicals or organically as a byproduct of corn fermentation. **Naturally:** by bacterial fermentation of carbohydrates such as glucose, sucrose, or lactose by many species (Lactobacillus, Bifidobacterium, Streptococcus) Natural constituent of some

methods

methods **Naturally:** by bacterial fermentation dietary fibre in

the colon

the colon

feedstuffs

Iceland moss.

anhydride

tamarinds)

oxygen

**Synthetically:** by a fermentation process **Naturally:** in a variety of fruits (most notably citrus fruitslemons, limes) and vegetables

**Synthetically:** by partial oxidation of toluene with

**Naturally:** in many plants as an intermediate in the formation of other compounds

**Synthetically:** by several different chemical pathways **Naturally:** in certain berries

**Synthetically:** from malic acid **Naturally:** in fumitory (Fumaria officinalis), bolete mushrooms (specifically Boletus fomentarius var. pseudo-igniarius), lichen, and

**Synthetically:** from maleic

**Naturally:** in apples and in many other fruits (mostly in unripe fruits)

**Synthetically:** by chemical reactions of maleic anhydrid **Naturally:** in many plants (particularly grapes, bananas,

Liquid (in pure state) Colourles transparent, fuming

Liquid Colourless, Very volatile

Liquid (in pure state) Oily

Liquid Oily

Liquid (in pure state) colourless or slightly yellow

Solid white crystalline powder or granule form

Solid white crystalline powder

2.93 very soluble Liquid Strong acid

Solid colorless crystalline

Liquid / Solid white crystal or crystalline powder

**Acid Chemical name Formula pKa Solubility in** 

Formic Formic Acid HCOOH 3.75 soluble in all

Acetic Acetic Acid CH3COOH 4.76 soluble in all

Propionic 2-Propanoic Acid CH3CH2COOH 4.88 soluble in all

CH3CH(OH)

CH3CH:CHCH:

COOHCH2CH

COOHCH(OH) CH(OH) COOH

COOHCH2C(OH) (COOH)CH2 COOH

acid C6H5COOH 4.19

Table 1. List of acids and their properties

Butyric Butanoic Acid CH3CH2CH2

Lactic 2-Hydroxypropanoic Acid

Sorbic 2,4-Hexandienoic Acid

Malic Hydroxybutanedioic Acid

> 2-Hydroxy-1,2,3- Propanetricarboxylic

Benzenecarboxylic

Tartaric 2,3-Dihydroxy-Butanedioic Acid

Acid

Citric

Benzoic acid

Fumaric 2-Butenedioic Acid COOHCH:CH

Inorganic acids added to the pig diets are hydrochloric, sulfuric, and phosphoric acid. Organic and inorganic acids or/and salt form combinations are often used in commercially available acidifiers. The response to mixed acids is generally better than to single acids possibly due to dissociation properties of these acids at various locations in the pig's digestive tract (Hardy 2002; Franco et al. 2005; Partanen et al. 2007; Kasprowicz-Potocka et al. 2009).


