Bridging Gut and Brain Health: The Role of Probiotics, Nutraceuticals, and Neuronutrition in Human Health and Recovery

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Recent research has illuminated the significant interplay between the gut and brain, positioning both gut health and diet as cornerstones of overall wellness[1].  This connection is particularly impactful in two fields: the modulation of gastrointestinal health through probiotics and the support of post-stroke recovery through neuronutrition[2]. Numerous studies show that both neuronutrients and eating behavior, in general, could impact the pathogenesis of neurological disorders and also the cognitive and emotional states of the patients[3].

Two recent studies: one examining the role of probiotics in gastrointestinal health via the Aryl Hydrocarbon  Receptor (AhR) pathway[4], and the other detailing the potential of neuronutrition in enhancing neuroplasticity post-stroke add further understanding to the role of gastrointestinal health[5]. Both studies highlight how probiotics, nutraceuticals, and dietary choices shape human health by supporting inflammation management, gut-brain communication, and immune balance[6]. Together, they provide a comprehensive view of how targeted nutritional interventions can improve quality of life and recovery outcomes.

Unique Elements of Each Study

Probiotics and Gastrointestinal Health through the Aryl Hydrocarbon Receptor Pathway

The first study published in the journal Foods focuses on the unique influence of probiotics in modulating gastrointestinal health through the Aryl Hydrocarbon Receptor (AhR) pathway, a cytoplasmic receptor and transcription factor that plays a crucial role in various physiological functions, including immune tolerance, barrier function in the gut, and maintenance of intestinal homeostasis. Probiotics, particularly strains like Lactobacillus and Bifidobacterium, have long been recognised for their benefits in gut health, such as improving the intestinal barrier and reducing inflammation. However, this study sheds light on how probiotics interact at a cellular level by binding to AhR.

The activation of AhR by probiotic metabolites (especially tryptophan metabolites) plays a critical role in modulating gut immunity and enhancing intestinal integrity. Tryptophan, an essential amino acid obtained from protein-rich foods (e.g., poultry, eggs, dairy, nuts, and legumes), is metabolised in the gut by both host enzymes and the resident microbiota. Bacteria are crucial in converting tryptophan into various bioactive metabolites, including indole derivatives (such as indole-3-acetic acid), tryptamine, and kynurenine pathway intermediates.

AhR is a basic helix-loop-helix transcription factor activated by external ligands (e.g., pollutants) and internal ligands like bilirubin, biliverdin, and tryptamine. Dietary ligands such as 3,3′-diindolylmethane (DIM), indole-3-carbinol (I3C), curcumin, diosmin, and urolithin A also stimulate the AhR pathway[7]. AhR forms a cytoplasmic complex with Heat Shock Protein 90 (HSP90), p23, an XAP molecule, and Src kinase, ensuring proper folding and ligand recognition. Upon ligand binding, AhR translocates to the nucleus, where it dimerises with ARNT (Aryl Hydrocarbon Receptor Nuclear Translocator) and binds DNA at AhR response elements (AHRE), regulating genes such as CYP450. Beyond xenobiotic responses, AhR is essential for maintaining hematopoietic stem cells, regulating reproduction and sex hormones, supporting retinal health, and sustaining immune tolerance and gut barrier function[8]. By harnessing the AhR pathway, probiotics offer a promising avenue for maintaining gut health and mitigating gastrointestinal disease.

In summary, Lactobacillus and Bifidobacterium probiotics have been found to increase the production of specific metabolites that act as AhR ligands, promoting anti-inflammatory responses and improving intestinal barrier function. This process is particularly beneficial in populations with gut pathologies like colitis, coeliac disease, and conditions involving dysbiosis, where probiotic administration showed improved symptoms and reduced inflammation.

Neuronutrition in Post-Stroke Neurorehabilitation

The second study in the journal nutrients introduces neuronutrition as a crucial element in post-stroke recovery, emphasising the brain’s capacity for neuroplasticity. This emerging field of nutrition science advocates for targeted dietary interventions designed to optimise neural recovery and enhance rehabilitative outcomes. Neuronutrition focuses on providing nutrients that can support the brain’s functional restructuring post-stroke, highlighting the role of omega-3 fatty acids, choline, methyl folate, polyphenols, certain vitamins (like D, B12, and E), and minerals (such as zinc and magnesium)[9].

These nutrients are instrumental in promoting the body’s antioxidant defences, reducing oxidative stress, and balancing inflammation—all essential for neuroplasticity and brain recovery. Additionally, the study reveals the pivotal role of the gut-brain axis in stroke recovery, with dietary patterns that foster a balanced gut microbiota proving beneficial for both neuroprotection and functional recovery. By incorporating a personalised neuronutrition approach, clinicians can help patients achieve better neuro-rehabilitative outcomes through diet[10].

Gut brain axis and interaction with colon and brain organs outline diagram. Body digestive tract influence and bidirectional communication to nervous system and cognitive centers vector illustration.

Connecting Elements of Both Studies

Both studies emphasise the importance of a well-functioning gut-brain axis, and although they approach health from different perspectives—one focusing on gut health and the other on brain recovery—there are remarkable overlaps in their findings.

Gut Health and Neuroprotection: Both studies reveal how a balanced gut microbiota and strong intestinal barrier can reduce systemic inflammation, a factor critical to both gastrointestinal and neurological health. In the probiotics study, strains such as Lactobacillus reuteri and Bifidobacterium longum, not only support gut health, but also interact with pathways that reduce systemic inflammation, benefiting brain health indirectly. Similarly, the neuronutrition study underscores the role of anti-inflammatory diets (like the Mediterranean diet), which are rich in gut-beneficial fibres and probiotics, in fostering a balanced microbiome to support brain recovery.

Nutritional Synergies for Health and Recovery: Both studies identify specific nutrients and bioactive compounds that act on inflammatory pathways. Omega-3 fatty acids, polyphenols, and certain vitamins (e.g., vitamin D) demonstrate dual benefits, aiding gut and brain health. Omega-3s improve cell membrane fluidity, which is beneficial in neurorehabilitation, while also supporting a healthy microbiota composition. Similarly, polyphenols and vitamins E and C act as antioxidants, reducing inflammation and oxidative stress across bodily systems.

The Importance of Anti-Inflammatory Mechanisms: Inflammation is a common theme in both studies. By modulating AhR signalling in the gut, probiotics reduce pro-inflammatory markers, which may support a calmer systemic inflammatory response. In parallel, the neuronutrition study advocates for dietary patterns that emphasise anti-inflammatory foods, which can decrease oxidative damage and support neuroplasticity. Both approaches, therefore, highlight that controlling inflammation through diet or supplementation is key to optimising gut and brain health.

Recommended Supplements, Ingredients, and Probiotics

Based on the findings from both studies, here is a table of recommended food supplements, ingredients, and probiotics that may support gastrointestinal and neurological health.

Table: Recommended Supplements, Ingredients, and Probiotics

Supplement/Ingredient Source Potential Benefits Relevant Study
Omega-3 Fatty Acids Fish oils, flaxseeds, and supplements Supports neuroplasticity, reduces inflammation Neuronutrition in Stroke Recovery
Lactobacillus Reuteri Probiotic supplements Activates AhR, enhances gut health, reduces inflammation Probiotics for Gut Health
Polyphenols Green tea, berries, Grape pips. supplementation Antioxidant properties, supports brain health Both Studies
Vitamin D Sunlight, fortified foods, supplementation Immune modulation, supports brain recovery Neuronutrition in Stroke Recovery
Bifidobacterium Longum Probiotic supplements Strengthens gut barrier, influences AhR Probiotics for Gut Health
Zinc Red meats, nuts, legumes, and supplements Co-factor for antioxidant enzymes, supports immune balance Neuronutrition in Stroke Recovery
Curcumin Turmeric, and supplements containing curcumin Potent anti-inflammatory and antioxidant, aids both gut and brain health Both Studies
Vitamin B Complex Whole grains, meats, dairy and supplements Supports cellular energy, neuroprotection, and gut health Neuronutrition in Stroke Recovery
Dietary Fibre Fruits, vegetables, whole grains and supplemental forms Improves gut microbiota composition, supports gut-brain axis Both Studies
Lactobacillus Acidophilus Probiotic supplements Enhances SCFA production, influences gut-brain axis Probiotics for Gut Health

Conclusion

The intersection of gut and brain health offers promising avenues for therapeutic approaches, as evidenced by the findings of these studies. Probiotics and targeted dietary supplements play essential roles in supporting both gastrointestinal health and neuroplasticity. Through AhR signaling, probiotics like Lactobacillus and Bifidobacterium impact gut immunity and reduce systemic inflammation, which, in turn, benefits brain health. In parallel, neuronutrition emphasises the importance of dietary patterns rich in anti-inflammatory, antioxidant nutrients for enhancing post-stroke recovery.

Four spoons filled of supplements diffrent color and shape. As a concept of natural medicines. Preventive medicine.

References

[1] Sasso JM, Ammar RM, Tenchov R, Lemmel S, Kelber O, Grieswelle M, Zhou QA. Gut Microbiome-Brain Alliance: A Landscape View into Mental and Gastrointestinal Health and Disorders. ACS Chem Neurosci. 2023 May 17;14(10):1717-1763.

[2] Badaeva AV, Danilov AB, Clayton P, Moskalev AA, Karasev AV, Tarasevich AF, Vorobyeva YD, Novikov VN. Perspectives on Neuronutrition in Prevention and Treatment of Neurological Disorders. Nutrients. 2023 May 28;15(11):2505

[3] Nogueira-de-Almeida CA, Zotarelli-Filho IJ, Nogueirade-Almeida ME, Souza CG, Kemp VL, Ramos WS. Neuronutrients and Central Nervous System: A Systematic Review. Cent Nerv Syst Agents Med Chem. 2023;23(1):1-12

[4] De la Rosa González A, Guerra-Ojeda S, Camacho-Villa MA, Valls A, Alegre E, Quintero-Bernal R, Martorell P, Chenoll E, Serna-García M, Mauricio MD, et al. Effect of Probiotics on Gastrointestinal Health Through the Aryl Hydrocarbon Receptor Pathway: A Systematic Review. Foods. 2024; 13(21):3479.

[5] Ciancarelli I, Morone G, Iosa M, Cerasa A, Calabrò RS, Tozzi Ciancarelli MG. Neuronutrition and Its Impact on Post-Stroke Neurorehabilitation: Modulating Plasticity Through Diet. Nutrients. 2024; 16(21):3705.

[6] Berding K, Vlckova K, Marx W, Schellekens H, Stanton C, Clarke G, Jacka F, Dinan TG, Cryan JF. Diet and the Microbiota-Gut-Brain Axis: Sowing the Seeds of Good Mental Health. Adv Nutr. 2021 Jul 30;12(4):1239-1285.

[7] Larigot L, Juricek L, Dairou J, Coumoul X. AhR signaling pathways and regulatory functions. Biochim Open. 2018 Jun 11;7:1-9.

[8] Neavin DR, Liu D, Ray B, Weinshilboum RM. The Role of the Aryl Hydrocarbon Receptor (AHR) in Immune and Inflammatory Diseases. Int J Mol Sci. 2018 Dec 3;19(12):3851.

[9] Badaeva AV, Danilov AB, Clayton P, Moskalev AA, Karasev AV, Tarasevich AF, Vorobyeva YD, Novikov VN. Perspectives on Neuronutrition in Prevention and Treatment of Neurological Disorders. Nutrients. 2023 May 28;15(11):2505.

[10] Nogueira-de-Almeida CA, Zotarelli-Filho IJ, Nogueirade-Almeida ME, Souza CG, Kemp VL, Ramos WS. Neuronutrients and Central Nervous System: A Systematic Review. Cent Nerv Syst Agents Med Chem. 2023;23(1):1-12.

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