Intelligent Biological Networks: Improving Anti-Microbial Resistance Resilience through Nutritional Interventions to Understand Protozoal Gut Infections

Abstract

Enteric protozoan pathogenic infections significantly contribute to the global burden of gastrointestinal illnesses. Their occurrence is considerable within remote and indigenous communities and regions due to reduced access to clean water and adequate sanitation. The robustness of these pathogens leads to a requirement of harsh treatment methods, such as medicinal drugs or antibiotics. However, in addition to protozoal infection itself, these treatments impact the gut microbiome and create dysbiosis. This often leads to opportunistic pathogen invasion, anti-microbial resistance, or functional gastrointestinal disorders, such as irritable bowel syndrome. Moreover, these impacts do not remain confined to the gut and are reflected across the gut-brain, gut-liver, and gut-lung axes, among others. Therefore, apart from medicinal treatment, nutritional supplementation is also a key aspect of providing recovery from this dysbiosis. Future proteins, prebiotics, probiotics, synbiotics, and food formulations offer a good solution to remedy this dysbiosis. Furthermore, nutritional supplementation also helps to build resilience against opportunistic pathogens and potential future infections and disorders that may arise due to the dysbiosis. Systems biology techniques have shown to be highly effective tools to understand the biochemistry of these processes. Systems biology techniques characterize the fundamental host-pathogen interaction biochemical pathways at various infection and recovery stages. This same mechanism also allows the impact of the abovementioned treatment methods of gut microbiome remediation to be tracked. This manuscript discusses system biology approaches, analytical techniques, and interaction and association networks, to understand (1) infection mechanisms and current global status; (2) cross-organ impacts of dysbiosis, particularly within the gut-liver and gut-lung axes; and (3) nutritional interventions. This study highlights the impact of anti-microbial resistance and multi-drug resistance from the perspective of protozoal infections. It also highlights the role of nutritional interventions to add resilience against the chronic problems caused by these phenomena.

Keywords: Cryptosporidium; Entamoeba; Giardia; anti-microbial resistance; multi-drug resistance; multiomics; postbiotics; prebiotics; probiotic; synbiotics; systems biology.

Figure 1

Global distribution of estimated deaths caused by diarrheal infections per 100,000 people in 2019 [7]. The interactive map can be obtained from https://ourworldindata.org/grapher/diarrheal-disease-death-rates (accessed on 28 June 2023). All visualizations, data, and code produced by “Our World in Data” are completely open access under the Creative Commons BY license.

Figure 2

A general life cycle and growth stages of protozoan enteric parasites, with Cryptosporidium and Giardia as examples. Note: This is a generalized outlay, with each protozoan discussed here showing minor variations in their respective cycles. Other protozoal parasites show slightly different life cycles than the ones represented. Created with Biorender.com.

Figure 3

A general representation of the host organs directly and indirectly affected by the enteric protozoan parasite infection. Created with Biorender.com.

Figure 4

Interaction and association networks: (A) representing regulatory functions and functional expression at various levels and (B) representing the changes caused during disease, with regulatory components of (a) present/absent key component (green: presence, red: absence); (b) misregulated gene expression causing over/underexpression (node size: expression level); (c) absence/erroneous interactions (dotted lines represent erroneous interactions); (d) misregulated directions (misdirected arrows); (e) interaction impact (arrow thicknesses + numbers). Figure courtesy of Jinawath, et al. [120]. Distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/) (accessed on 30 April 2023).