Relevance of organ(s)-on-a-chip systems to the investigation of food-gut microbiota-host interactions

Figures & data

Figure 1. Advantages and limitations of the different models for the study of host-microbiota-food interactions. Created with BioRender.com.

Figure 2. Applications of the gut-on-a-chip technology. Created with BioRender.com.

Figure 3. Anatomy and histology of the human gastrointestinal tract. Created with BioRender.com.

Table 1. Some examples of microbial metabolites in fermented foods.

Microbial metabolites	Produced by (examples)	Function / benefit	Reference
Short-chain fatty acids	Lactobacillus sp, Bifidobacterium sp	Anti-inflammatory, anti-proliferative, anti-carcinogenic	(Collado et al. 2019; Onyszkiewicz et al. 2019; Shimizu et al. 2019; Annunziata et al. 2020)
β-galactosidase	Bifidobacterium infantis CCRC 14633, B. longum CCRC 15708, B. longum CCRC15708, Lactobacillus sp., S. thermophilus	Improve lactose digestion	(Sangwan et al. 2015; Marco et al. 2017; Saqib et al. 2017)
Conjugated linoleic acid (CLA)	Lc. lactis, Lb. acidophilus, Lb. casei, Lb. plantarum, Lb. rhamnosus, Lb. delbrueckii	Oxidative stress improvement	(Linares et al. 2017)
Exopolysaccharides (EPSs) e.g., kefiran	S. thermophilus, Lb. delbrueckii subsp. bulgaricus	Cholesterol-lowering, antidiabetic, antioxidant, immunomodulatory	(Nampoothiri et al. 2017; Şanlier et al. 2019; Vinderola et al. 2019)
Teichoic acids	Lb. plantarum, Lb. rhamnosus, Lb. acidophilus	Anti-inflammatory and immunomodulatory	(Grangette et al. 2005; Konstantinov et al. 2008; Lebeer et al. 2012)
Vitamins B-group (B1, B2, B9) Menaquinone (K2)	Lb. casei KNE-1, S. thermophilus, Lb. delbrueckii, Lb. amylovorus L. lactis, Lb. brevis BGZLS10-17	Activation hepatic coagulation factors, amino acid metabolism, DNA replication and repair, cell division	(Walther et al. 2013; Linares et al. 2017; Saubade et al. 2017)
Gamma-aminobutyric acid (GABA)	Lb. casei, Lb. plantarum, S. thermophilus, Lb. brevis, Lc. lactis	Neurotransmitter, lowers blood pressure, relaxes muscles, reduces psychological stress, strengths gut barrier	(Pessione and Cirrincione 2016; Linares et al. 2017; Şanlier et al. 2019; Sokovic Bajic et al. 2019; Linares et al. 2016)
ACE-inhibiting peptides	Lb. helveticus, Lb. casei, Lb. delbrueckii, Lb. plantarum, Lc. lactis, S. thermophilus	Antihypertensive	(Shakerian et al. 2015; Li et al. 2017)
Antimicrobial peptides	Lc. lactis, Lb. plantarum, S. thermophiles, Lb. amylovorus	Control of pathogens	(And and Hoover 2003; Cotter et al. 2005; Silva et al. 2018; Garcia-Gutierrez 2019)
Phytase producers	Lb. plantarum, Lb. amylovorus, Lb. acidophilus	Hydrolase phytates, releasing minerals, chelating minerals and reducing bioavailability	(Sharma et al. 2020)
Anti-biogenic amines	Bacillus sp	Degradation of biogenic amines in fermented foods	(Spano et al. 2010; Barbieri et al. 2019; Mah et al. 2019)

Figure 4. Examples of different complexity levels in gut-on-a-chip systems that use immortalised cells to study the interactions with gut microbiota. The example in the upper position represents the first study that co-cultured L. rhamnosus GG with Caco-2 cells (Kim et al. 2012). On the right hand side, another system incorporated Human Peripheral Blood Mononuclear Cells (PBMCs) to further study the gut-immune system interactions, like in the Humix system, that also allowed the growth of anaerobes such as Bacteroides caccae (Eain et al. 2017). On the right hand side, a representation of the system generated by Jalili-Firoozinezhad et al, including endothelial cells and a complex gut microbiota from humanised mice (Jalili-Firoozinezhad et al. 2019). Created with Biorender.com.

Figure 5. Challenges and future directions of OoC technologies.

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