Antibiotic Alternatives: A Ray of Hope in The ERA of Increasing Antimicrobial Resistance

Antibiotics have been used in animal feed for growth promotion at lower or sub-therapeutic doses for many years. Due to their beneficial effect, AGP became popular and is commonly used! The indiscriminate usage with higher dosages expects better returns but this led to AMR and most of them became resistant. The worldwide health industry started thinking deeply about AMR and the European Union (EU) was the first to act on it whereas the global use is still increasing. Although the average consumption of antimicrobials is highly variable between countries, China is the largest consumer with 318 mg /population correction unit (PCU*). 

Globally over 70% of total antimicrobials produced are used in commercial animal production (Van Boeckel et al., 2017). In contrast, about 40% of antimicrobials’ sales in U.S. in food-producing animals have been reduced since 2015. Change in the consumer’s preferences is one of the reasons. Considering this impact, antibiotic alternatives became the need of an hour to minimise the progression of antimicrobial resistance (AMR). Antibiotic Alternative Therapy (AATs) is devised to combat AMR sustainably. Being advantageous over others, AAT has emerged as a dependable solution in recent times worldwide. Some of the available AATs in the animal feed nutrition market are as follows:

A. Phytobiotic:

Plant Extracts or Phytobiotics have been used for many years because of their antimicrobial, anti-inflammatory, antioxidant, and antiparasitic activities. Plant extracts include metabolites such as terpenoids, phenolics, glycosides, and alkaloids, present as alcohols, aldehydes, ketones, esters, ethers, and lactones. Plant extracts from aromatic spices (cinnamon, clove, etc.), pungent spices (pepper, garlic, and ginger), and herbs spices (rosemary, thyme, mint, moringa, etc.) are commonly used as feed additives. In animal nutrition, phytobiotics are included due to a wide range of activities like stimulation of feed intake, antimicrobial, coccidiostat, anthelmintic and immunostimulation. In addition, phytobiotics are natural and cost-effective, leave no residues in the end products hence, no withdrawal period. Beneficial effects of Phytobiotics have been proven in poultry for: 

• Growth promotion [improved body weight gain (BWG), feed conversion ratio (FCR)] 
• Gut function (improved nutrient digestibility, endogenous digestive enzyme secretion)
• Healthy microflora and integrity of GIT
• Improved immune health (stronger GALT)
• Optimized carcass quality (improved quality, reduced microbial load)
• Enhanced palatability, quality (sensory aspects) and
• Reduced mortality

Phytobiotics’ antimicrobial properties may be due to essential oils’ ability to penetrate the bacterial cell membrane, disintegrate membrane structure and cause ion leakage. Phytobiotic-based products contain a wide range of active ingredients formulated in a way to produce a desired effect like essential oils-based bronchodilators and anti-inflammatory agents deliver quicker symptomatic relief compared to allopathic as well as herbal (cough syrups) contemporaries.  Certain commonly used phytobiotics and their benefits are mentioned as follows-

• Cineol and eucalyptol from eucalyptus oil prevent infectious disease, dilate air sacs provide better air circulation and improve growth

• Thymol improves body weight and FCR
• Curcumin, an active ingredient of Curcuma longa (turmeric) has anti-inflammatory, antibacterial, antifungal, and anti-protozoal properties. Supplementation of turmeric powder could improve and maintain the egg production performance of the old laying hen at a higher level with a lower cholesterol content
• Garlic (Allium sativum) contains highly assimilable forms of selenium (selenomethionine, selenocysteine) which acts as an antioxidant to improve egg quality
• Bael (Aegle marmelos) contains bioactive compounds such as coumarin, xanthotoxol, imperatorin, aegeline, and marmeline having antidiarrheal, antimicrobial, antiviral, antipyretic, ulcer healing, diuretic, antifertility and anti-inflammatory properties

There are many other phytobiotics with no evidence of dysbiosis, AMR, or withdrawal.

B. Prebiotics and Probiotics:

•  The water should not contain any disinfectant or chlorine
• Water should be administered within 4-8 hours of mixingPrebiotics are indigestible carbohydrates source that selectively stimulates the growth of several beneficial bacteria in the colon. Prebiotics help to prevent the colonization of pathogens by creating unfavourable conditions like altering the pH of intestinal content. A good prebiotic could not be absorbed or hydrolysed in the GIT, it must be a selective substrate for a limited number of beneficial bacteria in the colon stimulating their growth and activating their metabolic function eventually resulting in the healthier colon microflora. The common prebiotics include oligofructose, fructans, inulin, fructo-oligosaccharides, galactan, galacto-oligosaccharides, resistant starch, pectin, etc. In simple terms, prebiotics should provide energy, metabolic substrate and essential micronutrients to the selected beneficial microbes.

Probiotics are live strains of selective microorganisms that when administered in an adequate amount confer a health benefit on the host. Microbes are selected based on their health-beneficial effects, and adaptability to the conditions in feed and the gastrointestinal tract. Probiotics have a beneficial effect like stimulating growth and improving immunity. Bifidobacterium, and lactobacillus, the useful bacteria found in the digestive system have mannanase enzymes and selectively bind mannan oligosaccharides (MOS). Feeding chickens with MOS significantly increases the length of the villi. The most selected effective and beneficial probiotics are Gram-positive bacteria belonging to Bacillus, Enterococcus, Lactobacillus, Pediococcus, and Streptococcus. Yeast and fungi are also used as probiotics. The dose recommendation for most of the probiotic strains is 1X109 colony-forming units (CFU/KG) of feed. 

Factors that should be considered when mixing probiotics-

C. Organic acids:

Organic acids have a significant role in reducing pH in the gut of poultry chickens. Reduction in pH causes acidification of the GIT thereby increasing the activity of the protease enzyme and improving nutrient utilization. The most known organic acids are acetic, formic, butyric, and propionic acids (simple monocarboxylic acids), malic, lactic, and tartaric acids (carboxylic acids carrying a hydroxyl group on alpha carbon). Moreover, they have been reported to be good at fighting against pathogenic bacteria. Organic acids also decrease colonization of pathogens such as Salmonella and E. coli which are known to damage epithelial cells of intestinal wall. 

• Ascorbic acid and citric acids increase the permeability of the bacterial cell, cause interference with membrane proteins, improve proliferation of epithelial cells of the GIT and increase villi height.
• Citric acid improves ileal digestibility, epithelial cell proliferation and villi height.
• Propionic acid increases the digestibility and availability of calcium and phosphorus.  
• Butyrate increases body weight and improves feed efficiency.

Conclusion:

Antibiotic alternatives have the potential to reduce dependency on antimicrobials.  To combat the current problem of anti-microbial resistance, the use of antibiotic alternatives for growth promotion appears to be an effective solution. Among all the options available in the market phytobiotics, probiotics, synbiotics and organic acids are the most widely accepted. Among these options, phytobiotics seem to be most promising one as they are of natural origin and generally recognised as safe. Phytobiotics contain a broad number of pharmacologically active substances resulting in pleiotropic effects. Additionally, phytobiotics are cost-effective and convenient to use with insignificant chances of negative effects. Therefore, promoting the usage of antibiotic alternatives is need of the hour to maintain sustainability for future generations. 

Vocabulary:

PCU* = A kilogram of animal product