*Bovine Respiratory Disease in Feedlot Cattle: Antimicrobial Resistance in Bovine Respiratory… DOI: http://dx.doi.org/10.5772/intechopen.81718*

antimicrobial compounds such as lactic acid and bacteriocins. They can also prevent adherence of pathogenic bacteria to the host cells via competitive exclusion, as probiotic strains use the same binding sites as the pathogenic bacteria or downregulate the expression of pathogen-binding sites [37]. Probiotic *Lactobacilli* have also been reported to preserve intestinal epithelial barrier function through stimulating mucin secretion, strengthening tight junction and preventing epithelial cell death and thereby inhibit pathogen translocation [37].

In addition, probiotics have the potential to boost host immune defenses against pathogens by modulating immune response [39]. Probiotics regulate innate and adaptive immune response by modulating immune cells and cytokine production via toll-like receptor-regulated signaling pathways [40]. Probiotic-induced alterations in the functions of dendritic cells, macrophages and T lymphocytes have been documented. For example, probiotic *Lactobacillus* strains modulated dendritic cells and thereby altered cell surface antigen expression and cytokine production in dendritic cells [37, 40]. Additionally, the impact of lactobacillus strains on macrophage function and its TNF-α production capacity has also been reported [41]. Probiotic bacteria *L. acidophilus* influenced the activity of regulatory T cells (Tregs) *in vitro* and *in vivo* in mice [42]. Tregs play a vital role in suppressing inflammation and maintaining immune tolerance.

Modulating the balance of pro- and anti-inflammatory cytokine production is one of the most important mechanisms through which probiotics protect the host from pathogen-induced injury and inflammation [43]. Probiotic bacteria have induced anti-inflammatory cytokine, IL-10, in dendritic and regulatory T cells [43]. IL-10, also known as the master regulator of immunity to infection, plays an essential role in facilitating the optimal pathogen clearance by inhibiting the activity of Th1 cells, NK cells and macrophages [44]. In addition, probiotics inhibit pro-inflammatory cytokine production and thereby prevent excessive inflammation. Probiotic strain *L. rhamnosus* GG inhibited the LPS-stimulated TNF-α production in murine macrophages [45]. Also, *L. rhamnosus* GR-1 strain has significantly or partially reduced LPS-induced number of proinflammatory cytokines including TNF, IFN-γ, IL-1β, IL-2 and IL-6 in human decidual cells [46]. Of note, the immune modulation properties of probiotics are species- and strain-specific, and therefore, different species or different strains within a species are expected to have different immunomodulation properties [37].

The role of probiotics on the local microbiota starts to be better understood due to the completion of the human genome project and the development of next generation DNA sequencing platforms that enabled a deeper understanding of the structure and composition of the host microbiome. Studies suggest that probiotics may re-establish the composition of the gut microbiota and confer beneficial effects on the gut microbial communities [47, 48]. However, there is limited information available with respect to the effects of probiotics on respiratory microbiota. A very recently published study showed that the oral probiotics alter respiratory microbiota of healthy cats [49]. The orally ingested probiotics were detected in the respiratory tract of the cat and were also associated with changes in richness and the overall composition of colonizing microbial populations of the respiratory tract. This observation points out that oral probiotics could alter the respiratory microbiota.

## *3.1.2 Using probiotics to mitigate BRD bacterial pathogens*

Beneficial effects of probiotics in the prevention and control of human respiratory tract infections have been studied. For example, probiotic strain *Streptococcus salivarius* K12 can mitigate pharyngitis by inhibiting the colonization of pathogen

*Bacterial Cattle Diseases*

(e.g. *E. coli*) via conjugation [29].

obesity [35] have been identified.

*3.1.1 Mechanisms of probiotic action*

**pathogens**

**3.1 Probiotics**

commonly used as metaphylaxis. Furthermore, Snyder et al. [14] also reported that a significant increase (from 3.7 to 99.2%) in the prevalence of *M. haemolytica* isolates resistant to tulathromycin in newly received feedlot cattle (n = 169) within

Three or more resistant genes have been detected from *M. haemolytica* and *P. multocida* [15, 29]. These resistant genes are most likely occurring from *de novo* mutation or being acquired from other bacteria. It has been reported that some resistant genes present in BRD bacterial pathogens are being encoded in selftransmissible conjugative elements [15]. Klima et al. [29] identified *M. haemolytica, P. multocida* and *H. somni* isolates from the US and Albertan feedlots that contain integrative conjugative elements (ICE) that conferred resistance up to seven different antimicrobial classes. These ICE can be transferred not only from one BRD pathogens to another BRD pathogen but also to other non-BRD-related bacteria

The resistant BRD-related pathogens can not only cause substantial profitability

losses to the beef industry and animal welfare issues due to the higher disease relapse and mortality rate but also pose potential threat to the public health given the possibility of these transferable elements carrying resistant genes transfer into zoonotic pathogens. Therefore, counteracting measurements to reduce the develop-

**3. Alternative antimicrobial approaches to mitigate BRD bacterial** 

Probiotics are defined as "live microorganisms administered in adequate amounts that confer a beneficial health effect on the host" [32]. The scientific recognition of the health-promoting properties of live microbes began in the early 1900s when a Ukrainian scientist, Elias Metchnikoff, hypothesized that the beneficial microbes present in fermented milk could normalize bowel health and prolong life by inhibiting 'putrefactive' bacteria in the gut [32]. Then, lactic acid bacteria (LAB) strains isolated from fermented milk were commercialized with the intention to treat diarrhea in French children in 1906. The term probiotics has been used since 1962. In the past 2 decades, a significant research attention has been given to probiotics, and beneficial effects of probiotics for the mitigation of infections of oral cavity; respiratory, urogenital and gastrointestinal tract [33]; cancer [34] and

Bacteria being used as probiotics today include LAB, non-pathogenic *Escherichia coli* and *Bacilli* [36]. The *Lactobacilli* and *Bifidobacteria* genera are the most commonly used as probiotics due to their specific health benefits, high safety profile, and stability [37, 38]. Probiotic bacterium possess unique genetic tools, special membrane structure and composition that allow them to survive under different environmental conditions after ingestion, adhere to the target niche, adapt to

Probiotics deliver their beneficial effects to the host through direct inhibition against potential pathogenic bacteria, improving the epithelial barrier function, stimulating the host immune system and re-establishing the commensal microbial community [37]. Probiotic bacteria can directly inhibit pathogens by producing

special nutrition conditions and integrate with the local microbiota [37].

ment and spread of AMR in BRD pathogens are urgently needed.

2 weeks after tulathromycin was given as metaphylaxis.

**22**

*Streptococcus pyogenes* and stimulating anti-inflammatory response in epithelial cells [50, 51]. A recent study revealed that the relative abundance of nasopharyngeal LAB in cattle entering the feedlot was significantly greater in animals that remained healthy compared with those that developed BRD [52], suggesting that a certain LAB are important to bovine respiratory mucosal health. Furthermore, an *in vitro* pilot study that we conducted to test antimicrobial properties of commercially available LAB strains (*Lactobacillus*) against *M. haemolytica* demonstrated the possibility of using probiotics to mitigate BRD pathogens [53]. The *Lactobacillus* strains isolated from the nasopharynx of healthy feedlot cattle displayed antimicrobial activity against the growth of *M. haemolytica in vitro* [54]. We also recently reported that the intranasal inoculation of *Lactobacillus* spp. strains inhibits the colonization of *M. haemolytica* S1 into the nasopharynx of dairy calves challenged with *M. haemolytica* S1 (Amat et al., unpublished data). These studies suggest the potential application of probiotics to mitigate BRD bacterial pathogens in feedlot cattle as an alternative to antimicrobial metaphylaxis.
