BACKGROUND: Indian system of Traditional medicine, AYUSH (Ayurveda, Yoga, Unani, Siddha, and Homeopathy) has great potential with a History of Safe Use (HOSU) of thousands of medicinal plants included in pharmacopoeias. The multi-targeted approach of phytoconstituents present in different traditionally used medicinal plants makes them suitable candidates for research against various infective pathogens. MAP which is a dairy-borne pathogen is associated with the development of Johne\'s disease in ruminants and Crohn\'s disease like autoimmune disorders in human beings. There are no reliable treatment alternatives available against MAP, leaving surgical removal of intestines as the sole option. Hence, there exists an urgent need to search for leads against such infection.
OBJECTIVE: The present review has been conducted to find out the ethnopharmacological evidence about the potential of phytoconstituents against Mycobacterium avium subspecies paratuberculosis (MAP), along with the proposal of a potential phyto-MAP mechanism for the very first time taking anti-inflammatory, immunomodulatory, and anti-microbial traditional claims into consideration.
METHODS: We have analyzed and reviewed different volumes of the two main traditional scriptures of India i.e. Ayurvedic Pharmacopoeia of India (API) and Unani Pharmacopoeia of India (UPI), respectively-for identification of potential anti-MAP plants based on their claims for related disorders. These plants were further investigated systematically for their scientific publications of the last 20 years (2002-2022) available through electronic databases including Google Scholar, Pubmed, and Scopus. The studies conducted in vitro, cell lines, and in vivo levels were taken into consideration along with the associated mechanisms of phytoconstituents.
RESULTS: A total of 70 potential medicinal plants have been identified. Based on the ethnopharmacology, a potential phyto-paratuberculosis (Phyto-paraTB) mechanism has been proposed and out of 70, seven potential anti-MAP plants have been identified to have a great future as anti-MAP.
CONCLUSIONS: A novel and scientifically viable plan has been proposed for addressing anti-MAP plants for stimulating research against MAP and related disorders using mass-trusted AYUSH medicine, which can be used as an alternative remedy in resistance cases otherwise can be advocated as an adjuvant with modern treatments for better management of the disease.

Paratuberculosis, or Johne\'s Disease (JD) is a debilitating chronic enteritis mainly affecting ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). This organism causes worldwide economic losses to the livestock industry, and is of public health importance due to the potential zoonotic risk between MAP and Crohn\'s disease (CD) in humans. Without economical treatments, or a vaccine capable of preventing infection without causing cross-reactions with bovine tuberculosis, test-and-cull methods for disease control are imperative. Unfortunately, difficulties in diagnostics and long subclinical stage hinder adequate control and is further complicated by variation in MAP exposure outcome. Interestingly, the majority of infections result in asymptomatic presentation and never progress to clinical disease. One contributing factor is host genetics, where polymorphisms in innate immune genes have been found to influence resistance and susceptibility to disease. Candidate genes identified across studies overlap with those found in CD and tuberculosis including; Solute carrier family 11 member 1 gene (SLC11A1), Nucleotide-binding-oligomerization domain containing gene 2 (NOD2), Major histocompatibility complex type II (MHC-II), and Toll-like receptor (TLR) genes. This review will highlight evidence supporting the vital role of these genes in MAP infection outcome, associated challenges, and implications for the future of JD research.

Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of paratuberculosis (ParaTB or Johne\'s disease), a contagious, chronic and typically fatal enteric disease of domestic and non-domestic ruminants. Clinically affected animals present wasting and emaciation. However, MAP can also infect non-ruminant animal species with less specific signs. Zoological gardens harbor various populations of diverse animal species, which are managed on limited space at higher than natural densities. Hence, they are predisposed to endemic trans-species pathogen distribution. Information about the incidence and prevalence of MAP infections in zoological gardens and the resulting potential threat to exotic and endangered species are rare. Due to unclear pathogenesis, chronicity of disease as well as the unknown cross-species accuracy of diagnostic tests, diagnosis and surveillance of MAP and ParaTB is challenging. Differentiation between uninfected shedders of ingested bacteria; subclinically infected individuals; and preclinically diseased animals, which may subsequently develop clinical signs after long incubation periods, is crucial for the interpretation of positive test results in animals and the resulting consequences in their management. This review summarizes published data from the current literature on occurrence of MAP infection and disease in susceptible and affected zoo animal species as well as the applied diagnostic methods and measures. Clinical signs indicative for ParaTB, pathological findings and reports on detection, transmission and epidemiology in zoo animals are included. Furthermore, case reports were re-evaluated for incorporation into accepted consistent terminologies and case definitions.

This systematic review-meta-analysis appraises and summarizes all the available research (128 papers) on the zoonotic potential of Mycobacterium avium ssp. paratuberculosis. The latter has been debated for a century due to pathogenic and clinical similarities between Johne\'s disease in ruminants and Crohn\'s disease (108 studies) in humans and recently for involvement in other human diseases; human immunodeficiency virus (HIV) infection (2), sarcoidosis (3), diabetes mellitus type 1 (T1DM) (7) and type 2 (3), multiple sclerosis (5) and Hashimoto\'s thyroiditis (2). Meta-analytical results indicated a significant positive association, consistently across different laboratory methods for Crohn\'s disease [odds ratio (OR) range 4·26-8·44], T1DM (OR range 2·91-9·95) and multiple sclerosis (OR range 6·5-7·99). The latter two and the thyroiditis hypothesis require further investigation to confirm the association. Meta-regression of Crohn\'s disease studies using DNA detection methods indicated that choice of primers and sampling frame (e.g. general population vs. hospital-based sample) explained a significant proportion of heterogeneity. Other epidemiological studies demonstrated a lack of association between high-risk occupations and development of Crohn\'s disease. Due to knowledge gaps in understanding the role of M. paratuberculosis in the development or progression of human disease, the evidence at present is not strong enough to inform the potential public health impact of M. paratuberculosis exposure.