Sugandha Asthana, Ph.D

Cerebral palsy (CP) is a neurodevelopmental disorder that affects different parts of the brain in neonates. For a very long time, it was thought that this condition arose due to delivery complications, including delayed delivery, premature birth, and hypoxic conditions generated during delivery. Still, even after managing these conditions, the incidence rate didn't decrease significantly. Multiple studies and years later, it was observed that CP is not just a perinatal condition but also antenatal and postnatal. In antenatal care, the mother's health is crucial. If the mother has any infectious disease, such as CMV, rubella, toxoplasmosis, or Zika virus, it can penetrate the placental barrier and infect the baby, resulting in CP. Other conditions such as diabetes, hypertension and thyroid conditions can also increase the risk of CP. Apart from this, CP also develops due to chromosomal mutations and epigenetic modifications.

Symptoms of CP depend on which area of the brain is affected. The cortex is affected in spastic CP, resulting in increased muscle tone and increased reflexes. In dyskinetic CP, the basal ganglia are affected, causing involuntary, uncontrolled and repetitive movements with fluctuating muscle tone. Ataxic CP occurs when the cerebellum is affected, causing loss of coordination with hypotonia. In most cases, spastic CP is common, but in some cases, different brain regions are affected, resulting in mixed CP with a wide array of symptoms.

With advances in treatments, including therapies and medicines, most symptoms of CP can be managed. Novel treatment ideas such as glial cell transplantations, nanomedicine and stem cell therapy are under investigation and hold a bright future. Neurogenerative therapies are also being researched. The goal of these studies is to replace lost or injured brain tissue to restore its structure and function. These studies are in the experimental phase and face numerous difficulties, including problems with safety, efficacy and ethics.

Many individuals with CP have achieved fame as actors, writers, activists and comedians. This condition might be limiting, but it certainly isn't limitless.

With the hardships faced by women in their everyday life, one would think that at least their bodies would be in support, but that's not so! Stiff Person Syndrome affects women twice as much as men. Although this disorder is so rare that it is seen in 1 in 1 million people, women are still not spared!

This rare condition is caused when antibodies are formed against Glutamic Acid Decarboxylase (GAD), the rate-limiting enzyme for the synthesis of the inhibitory gamma-aminobutyric acid (GABA). This amino acid is an inhibitory neurotransmitter of the brain, which prevents misfiring of neurons and maintains muscle movement. With antibodies against GABA, the first symptoms observed in patients occur in the form of leg stiffness. This stiffness carries upwards and reaches the spinal cord, causing spasms. A person suffering from this condition has difficulty bending, which is referred to as Tin-Man syndrome. Another unique symptom observed in these patients is that they are sensitive to noise triggers. A loud noise in any form — music, loud banging, honking — results in the triggering of spasms in all the affected muscles.

This disease has been misdiagnosed because it falls under numerous other disorders called GABA disorders, the most common being neuropathy and myelopathy. This misdiagnosis results in delaying or even wrong treatment. Numerous studies are underway to distinguish this condition from other diseases and are focusing solely on its physical symptoms. Unfortunately, there is no cure, and symptomatic relief is given to patients via benzodiazepines, baclofen, and other GABAergic agents. This enhances GABAergic neurotransmission, relieving muscle stiffness and spasms. Other treatment plans involve immunomodulatory treatments (e.g., IVIg, plasmapheresis, rituximab) aimed at modifying the underlying autoimmune response.

The human body is an enigma; the cells that are supposed to protect end up hurting us the most! Such a rare autoimmune disorder caught the eyes of researchers, and improvement in diagnosis is still underway. Since the cohort size is small, patients do end up suffering because of misdiagnosis. But one should never give up hope. With the advent of gene therapy, maybe there is a brighter future for all of them.

The winter in the United States was brutal this year. With the snowstorms, chilly winds, and extreme temperatures, going outside seemed like a thing of the past! It felt like I was back in 2020 and there was a lockdown in place. Days after days of never-ending snow where even the trees struggled to survive, I noticed something growing on the walls of my balcony. What can grow when even breathing hurts? Turns out it was a type of mold! Welcome to the world of extreme adventures, where only one thing survives: Extremophiles!

Extremophiles are organisms that can live in extreme climatic conditions and are termed as follows:

Type	Condition	Examples
Thermophiles	High temperatures	Thermus aquaticus, Pyrococcus furiosus
Psychrophiles	Low temperatures	Moraxella sp., Flavobacterium sp.
Halophiles	High salinity (2–6M NaCl)	Halobacterium, Haloferax
Acidophiles	Low pH (<3)	Penicillium sp., Sulfolobus solfataricus
Alkaliphiles	High pH (>9)	Alkalibacillus sp.
Radiophiles	High radiation	Porphyra rosengurttii, Deinococcus radiodurans

Extremophiles are very smart and are able to thrive in extreme conditions because of modified cell membranes, strong DNA repair mechanisms, and very stable enzymes, which help them withstand high pressure, high temperature, and high salt concentration.

In thermophiles, it has been observed that there are an abundance of tyrosine, glutamate, and leucine, which favors ionic interactions, rigidity, and hydrophobicity. The opposite is true for psychrophiles, which are abundant in amino acids such as threonine, methionine, phenylalanine, and serine. Thermophiles also have a very robust DNA polymerase that retains its stability at high temperatures. You would have used these polymerases in your work as well: Taq polymerase (from Thermus aquaticus) and Pfu polymerase (from Pyrococcus furiosus).

Other than its uses in the laboratory, various extremophiles are being used in biotechnology industries. An ongoing study by H. Abdulsalam focuses on using radiophiles to generate microbial fuel cells, which would be operative in high-radiation conditions. This can aid in space exploration and nuclear waste management! Imagine the power of such a small creature!

Uses of extremophiles are being explored across industries, including food, biomedical, and cosmetic. Although there are multiple processing and low-yield challenges, these small creatures hold much power and will help in advancing science!

"The conversation between food and gut is so loud that you can hear it echo throughout the whole body" — Sugandha Asthana

Abstract

Our diet not only determines the level of energy we will have throughout the day, but also affects our immune system, gut microbiota, and repair mechanisms after injury. Past research has shown that dietary patterns, specific nutrients and even meal timings can affect immune cell metabolism, microbiota environment and intestinal stem cell activity involved in repair and maintaining homeostasis. Fibre and fermented foods determine microbial diversity; fasting and calorie restriction modulate T-cell differentiation; micronutrients and amino acids, such as vitamin A and cysteine, directly influence epithelial cell fate and stem cell-mediated regeneration. This article offers the readers an overview of the "talk" that happens between food, microbiota and the immune system within the intestine and how the overall health of an individual gets affected because of diet. The goal of this study is to understand how food shapes our system and how we can take care of our body by just tweaking a few ingredients in our diet.

Diet and the gut microbiota: feeding an ecosystem

The intestinal tract is lined with millions of bacteria, forming a dynamic ecosystem are triggered by our diet. A diet rich in fibre, fruits and plant-based foods increases the growth of bacterial families such as Bifidobacteria and Lactobacilli. Increased growth of these microorganisms boosts production of short-chain fatty acids, which support integrity of intestinal cells and improve anti-inflammatory signalling pathways (Koelman et al., 2022; Tu et al., 2023). Figure 1 depicts an intestinal section containing the gut lumen, barrier, and tissues, which highlights how closely each part of the intestine is connected to the others.

In contrast, a diet rich in fats, sugar and ultra-processed foods reduces microbial diversity and favours the growth of bacteria associated with low levels of inflammation and metabolic dysfunction. This fact is supported by a study done by a group of scientists at Stanford University in 2021. They conducted the study on 36 healthy individuals as a 17-week randomised trial. They were divided into 2 groups: One group was given a high-fibre diet, whereas the other was given a high-fermented-food diet. At the end of the study, it was noticed that fibres increased glycan-degrading enzymes and microbial protein density but did not raise diversity. Whereas the group with fermented food in their diet had a steady incline of microbiome diversity and reduced 19 inflammatory cytokines, including IL6 and TNFα. Also, the new microbiota that was found was different from the original ecosystem, showing that fermented food can also nudge the ecosystem in a different direction (Wastyk et al., 2021).

The microbial changes shift the immune system into being more anti-inflammatory and help in the overall health of an individual. Short chain fatty acids (SCFAs) such as butyrate are known to directly regulate Treg and B-cells, and microbial metabolites interacting with epithelial and innate immune pathways reduces the gut irritability. This is why maintaining a healthy gut microbiota is crucial, as it can help in reducing chronic inflammation (Munteanu & Schwartz, 2022).

Nutrition as a control knob for immune cell metabolism

Immune cells can switch nutrient requirements and pathways depending on their growth or their usage. Pro-inflammatory macrophages (M1) use glycolysis for energy, while anti-inflammatory (M2) macrophages use fatty-acid oxidation. Naïve lymphocytes use the mitochondrial respiratory cycle for energy but switch to aerobic glycolysis when activated. Creating a calorie deficit environment by either intermittent fasting or maintaining a restrictive diet results in reprogramming of these immune cells and activating different transcription factors (Okawa et al., 2021).

Calorie-deficit conditions suppress the PI3K–Akt–mTOR axis and activate AMPK, sirtuins, and FoxO transcription factors. This shifts them from their proliferation stage to stress-resistant and regulatory functions. In autoimmune diseases, this is associated with reduced Th17 differentiation, an increase in Treg cells and enhanced M2 macrophages, causing reduced inflammation and improving symptomatic relief (Smith et al., 2018).

Another study observed that fasting reduced gut-associated lymphoid tissue (GALT) and diminished IgA responses, compromising mucosal immunity. Animal studies have reported that in fasting conditions, metabolic and immunological effects increased, leading to adverse effects. To have a better outcome, it was important to monitor timing, duration and age when following a restrictive diet (Paniagua, 2016). In ketogenic diets, ketone bodies like βhydroxybutyrate are produced, which activate stress sensors such as GCN2. This suppresses inflammatory T-cell differentiation, modulates gut immune responses and can cause relief in gut inflammatory conditions (Smith et al., 2018; Xia et al., 2018).

These interventions overlap with metabolic flexibility, which is the ability of tissues to switch between glucose and fatty acids depending on energy requirements. Loss of metabolic flexibility is linked to obesity, type 2 diabetes, and other chronic diseases. Dietary interventions that benefit immune balance also improve overall health by activating AMPK, PPARγ, and mitochondrial biogenesis. This helps in maintaining a homeostatic condition in the intestines (Okawa et al., 2021).

Micronutrients, macronutrients, and immune signalling

Regulators of immune responses include several vitamins, minerals and macronutrients such as fats. Vitamins A, C, D and B, along with zinc and selenium, are involved in innate and adaptive immune responses. They encourage cell proliferation, cytokine production and cell trafficking. For absorption of fat-soluble vitamins, it is important to have healthy fats in the diet (Tu et al., 2023).

Cholesterol, which has gained its image as the leading cause of cardiovascular diseases, has a concentration-dependent effect on the immune system. In low concentrations, cholesterol supports immune responses by maintaining lipid rafts, which are essential for T-cell activation, B-cell receptor signalling and antigen presentation (La Cava & Castaldo, 2025). At higher concentrations, cholesterol accumulates in immune cells, causing pro-inflammatory polarization, activating Toll-like receptors and inflammasomes (Tall & Yvan-Charvet, 2015). Polyunsaturated fatty acids (PUFAs) such as omega-3 and omega-6 are anti-inflammatory in effect.

Dietary control of intestinal stem cells and regeneration

Intestinal stem cells (ISCs) are located at the base of crypts and are continuously replenishing the epithelial lining. An example of crosstalk between ISCs and the immune system was observed in mouse models. It was observed that a cysteine-rich diet enhances intestinal regeneration following radiation injury. Cysteine was absorbed by SLC7A11 transporter and converted to CoA in epithelial cells. This increased production of T-cells and elevated IL-22, a cytokine. Both help in intestinal repair. Knockout mice of the transporter showed no regenerative effects, and only by adding CoA to their diet was the regenerative effect recapitulated. This study concluded that a single amino acid can have such an impact on the repair of cells after injury (Chi et al., 2025).

The effect of other nutrients and dietary patterns is summarised in Table 1.

Vitamin A is considered crucial as it is actively involved in determining the fate of enterocytes. In normal concentrations, retinoic acid binding receptors (RARs) bind to retinoic acid and "push" the progenitor cells to develop into enterocytes. This causes the intestines to absorb more food rather than produce mucous (Jijon et al., 2018; Munteanu & Schwartz, 2022).

Ketogenic diets inhibit histone deacetylases (HDACs), activating NOTCH signalling and maintaining ISC self-renewal, whereas high glucose suppresses the same ketone-driven pathway (Cheng et al., 2019; Marinou et al., 2011).

PPARγ is a nuclear receptor and transcription factor that regulates adipose tissue differentiation, glucose metabolism and immune function. A high-sugar and high-fat diet results in dysregulation of this transcription factor, causing hyperproliferation of intestinal cells, and is linked to tumour development (Hernandez-Quiles et al., 2021).

Fructose, in optimum quantity, helps normal epithelial cells withstand hypoxia-related stress by modulating glycolytic enzymes such as PKM1/PKM2. This promotes the growth of villi and improves nutrient absorption. In higher concentration, growth of villi gets dysregulated, increasing intestinal growth and causing colorectal cancer (Chica-Cid & Giraldez, 2022; Smith et al., 2018).

Table 1: Summary table — key nutrients and intestinal effects

Below is the summary table of nutrient-intestine interactions to show how diverse dietary inputs converge on stem cells, differentiation, and tumour risk.

Nutrient	Effect	Mechanism	Reference(s)
Vitamin A	↑ enterocyte differentiation	Vitamin A → retinoic acid → binds RAR (nuclear receptor) → activates genes for absorptive cell fate	(Lukonin et al., 2020)
Low vitamin A	↓ goblet cell differentiation	Disrupts the integrity of intestinal epithelial cells and the production of goblet cells → hampering immune response → inflammatory disorders of the intestine	(Jijon et al., 2018)
High fat	↑ ISC self-renewal, tumour risk	Fatty acids activate PPARα/δ (nuclear receptor) → β-catenin (Wnt pathway) + fatty acid oxidation → stem cells keep self-renewing instead of differentiating. If APC (tumour suppressor) is also lost, unchecked renewal = tumour	(Beyaz et al., 2016; Mana et al., 2021)
Ketogenic diet	↑ ISC self-renewal	Ketone bodies inhibit HDAC enzymes (which normally silence genes) → this activates NOTCH signalling → self-renewal is maintained	(Cheng et al., 2019)
High glucose	↓ ISC self-renewal	Glucose suppresses the same ketone-driven pathway	(Cheng et al., 2019)
High fat + high sugar	↑ ISC proliferation	Activates PPARγ (a different PPAR subtype than the high-fat-alone pathway) → hyperproliferation	(Aliluev et al., 2021)
Fructose	↑ intestinal cell survival	Fructose-1-phosphate inhibits pyruvate kinase M2 (a glycolytic enzyme) → shifts metabolism to favour survival under low-oxygen gut conditions	(Taylor et al., 2021)

Practical implications and outlook

In this article, a connection between what we eat and how our body responds is observed. They interact with each other and affect microbiota, immune response and regeneration of cells. Diets rich in fibre, fermented foods and more balanced nutrients can increase microbial diversity, reduce inflammation and support barrier function. Along with diet, the timing of food intake also matters. Intermittent fasting with the right balance of food can help in the recalibration of the immune system, improving overall health. The worst diet that we can follow is high-fat and high-sugar. This not only disrupts the microbiota of the gut, but it also disrupts the gut barrier and causes activation of pro-inflammatory responses. If left unchecked, they can cause unregulated cell proliferation and are a risk for tumour development. Thus, maintaining a balanced diet is crucial for healthier and longer living.

Author’s message to the readers: Your diet is important not just for your health but also for immunity and for maintaining a healthy microflora in the body. A good diet with a balance of fats, fibres, fermented foods, macro and micronutrients helps in maintaining homeostasis within the body. While working on this article, I realized minor changes in the diet can help us maintain a healthy lifestyle.