Managing necrotic enteritis in an antibiotic-free environment -- A nutritional approach

The move towards antibiotic-free poultry production has created new challenges for the sector.


By Franco Mussini PhD, Elizabeth Kim PhD

The move towards antibiotic-free poultry production has created new challenges for the sector. Particularly, how to control the very real risk of a necrotic enteritis outbreak. With no ‘silver bullet’ yet identified, members of the North American technical team at Danisco Animal Nutrition explain why adopting an integrated feed strategy designed to combat known triggers of this financially-devastating disease is currently the most logical solution.  

Cause and effect

A common and highly infectious disease, necrotic enteritis (NE) is caused by a gram-positive, anaerobic bacterium known as Clostridium perfringens and has traditionally been controlled by the use of antibiotic doses in animal feed and water. However, consumer concerns around public health, as well as guidelines from the Food and Drug Administration (FDA) limiting the use of antibiotics in commercial farms, means that this established practice is increasingly being phased out.

This transition has left poultry producers without one of the key tools to fight this unpredictable disease and urgently in need of an alternative strategy. Yet, although commercially-available feed additives are widely recognized as offering significant potential, no single product has been found to offer a simple replacement.

So, rather than look for a straightforward substitute for antibiotics, the most logical approach is to tackle the conditions that are known to cause NE outbreaks; specifically, the multiple factors that combine to create the perfect environment for C. perfingens to proliferate.

Only by looking at this complex issue from every angle can producers hope to reduce the probability of the disease occurring in flocks. In each case, a thorough examination of each element helps to provide a framework for potential feed solutions.

Crude protein

Studies have identified a link between high levels of crude protein and C. perfringens counts, with the corresponding rise varying depending on the protein source. However, to fully understand the impact of crude protein intake, it is important to also examine other equally influential factors in detail.  

For example, the type of protein (undigestible or digestible) plays an important role. Studies show that the highest undigestible fraction correlates to higher C. perfingens counts. An outcome which can be explained by the undigested protein fraction moving from the small intestine to the hindgut, where it is fermented by nitrogen-using bacteria, such as C. perfringens.

Research has also shown that part of the bird’s uric acid elimination ends up back in the hindgut, where a portion acts as a potential substrate for caeca bacteria and this, again, encourages the growth of C. perfringens populations.

In addition, the presence of phytate in animal feed can also increase levels of crude protein in the hindgut. Firstly, due to its ability to bind and create a phytate/protein complex at gizzard level which is very difficult to break down - even in the presence of older generation exogenous phytases. And secondly, because it irritates the small intestinal epithelium which reacts by increasing secretions of the amino acid-rich mucus. This excess then provides more substrate for C. perfingens which further benefits its proliferation.

Potential solutions: 

  • Use of highly digestible protein sources and properly balanced rations to reduce both undigestible protein and digestible non-essential amino acids and so decrease uric acid production.

  • Use of synthetic amino acids to reduce crude protein levels, even when this requires forcing them into the diet and increasing feed costs; thus reducing potential substrate for C. perfingens growth.

  • Use of protease to reduce the undigestible fraction, along with the proper use of validated matrix to decrease formulated crude protein levels.

  • Use of exogenous phytase that shows high activity at low pH to break down the phytate early in the digestion process, which would otherwise act as substrate for nitrogen-using, potentially pathogenic bacteria.


Both the type and level of calcium can reportedly increase the incidence of NE and mortality related to this disease. Of particular relevance is data showing that high levels of calcium, as well as the use of small particle limestone/highly soluble calcium impact levels of C. perfringens. However, it is important to understand the different reasons why.

Calcium can bind with phytate and protein. This reduces protein digestibility and so increases the amount of protein that can reach the hindgut to be fermented by pathogenic bacteria.

At the same time, calcium has an influence on the alpha and the NetB toxins produced by C. perfringens. Alpha toxins, for example, requires a calcium ion to bind to the cell membrane and higher levels of calcium facilitate this process. Whereas, the NetB toxins can bind without calcium ions but, once bound, open pores in the cell membrane which allows ions - such as calcium - to enter and so triggers a cascade of reactions that eventually lead to the cell death.

Potential solutions:

  • Closely monitor calcium levels in finished feed.

  • Look for hidden sources in micro ingredients, as well as macro ingredients such as soybean meal, meat and bone meal, etc.

  • Adjust added calcium when using phytase, which releases calcium from phytate-bound calcium.

  • For broiler diets, use limestone with at least a particle size of 350 microns.

Coccidiosis/Coccidia challenge

Multiple peer reviewed papers refer to a NE model where high crude protein diets together with a coccidia challenge is enough to trigger NE. In terms of the coccidia challenge, there are a number of mechanisms which contribute to this effect.

Coccidia cycling damages the small intestine, which leads to inflammation, increased mucin production and premature sloughing of enterocytes off the villi; so increasing endogenous loss and the by-pass of native nutrients to the lower gut.

At the same time, the damaged enterocytes and shortened villi cannot efficiently digest and absorb nutrients, which adds to nutrient movement to the lower gut. Not only that, they also allow plasma proteins to leak into the lumen and so further increase the amount of protein moving into the large intestine and ceca.

Potential solutions:

  • Closely monitor coccidiosis control programs and use proven feed additives, such as natural betaine, to aid enterocyte integrity on a cellular level during cocci vaccination.

Gut health

As already, discussed, NE in broilers has been attributed to strains of C perfringens that produce alpha and NetB toxins which attack and reduce the surface area of the intestinal mucosal lining. An action which not only reduces bird performance and weight gain, but also creates conditions in the gut that are ideal for the proliferation of pathogenic bacteria.

Potential solutions:

The use of poultry Direct Fed Microorganisms can help to shift the gut microbiome towards a healthy and steady state; favoring commensal bacteria and balanced pH. This live microbial feed supplement beneficially affects the host and has several modes of action which modify the gastrointestinal microbiome and impact C. perfringens.

DFMs consume competing substrate which in turn creates an inhospitable environment such as suboptimal pH. The addition of these bacterial species can work by improving host immune function and gut morphology. This leads to a corresponding reduction in Clostridia adhering to the mucosal lining which improves intestinal integrity10.  A healthy immune response and gut morphology helps reduce the likelihood of infection by opportunistic pathogens8.

Maintaining the gut mucosal lining is also important to keeping gut microbiota inside the intestine rather than translocating outside of the gut. This is especially key in young birds with undeveloped gut microbiomes and lower immune function. Supporting the right balance of gut microbiota in the developing chick is crucial to reduce the likelihood of NE in broilers. In this context, the addition of DFM to early chick diets can improve the intestinal epithelium and move the rapidly developing chick gut towards a more beneficial and robust gut microbiome - so decreasing the potential impact of NE outbreaks.

In addition, a key co-factor in preventing NE outbreaks is coccidiosis control. Particularly given that co-infection with Eimera has been shown to increase mortality and incidence of NE. A DFM can support an existing cocci program and, in some cases, help to favorably shift the gut microbiome under cocci challenged conditions. 

The addition of in-feed DFM also has wider benefits in terms of housing management. An issue which has become even more important due to the relatively recent removal of antibiotic growth promoters (AGPs), which have traditionally been used to help keep these hardy bacteria in check.

DFM species that colonize the gut will flow with digesta to be excreted and consume available substrates in the environment, such as poultry litter and bedding, and also release bound water. This can potentially result in a shift in litter bacterial diversity which reduces the growth of opportunistic pathogens. An outcome which is critical given that C. perfringens produce spores capable of surviving even under difficult conditions. 


[1] Y.X. Feng, V. Muller, B. Friedrich, T. Risler, F. Lang. Clinical significance of cell volume regulation. Wien Klin Wochenschr, 113 (2001), pp. 477-484

[2] F. Schliess, D. Häussinger. The cellular hydration state: a critical determinant for cell death and survival Biol Chem, 383 (2002), pp. 577-583

[3] F. Lang. Mechanisms and significance of cell volume regulation. J Am Coll Nutr, 26 (2007), pp. 613S-623S.)

[4] N.I. Dmitrieva, M.B. Burg. Hypertonic stress response. Mutat Res, 569 (2005), pp. 65-74.;

[5] R. Reinehr, D. Häussinger. Hyperosmotic activation of the CD95 death receptor system. Acta Physiol, 187 (2006), pp. 199-203.

[6] R. Gilles. “Compensatory” organic osmolytes in high osmolarity and dehydration stresses: history and perspectives. Comp Biochem Physiol, 117A (1997), pp. 279-290.

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