By Jugal Das & Soumya Puri
They have long been viewed as a digestive aid and a food that helps the body recover from a course of antibiotics. Now, a quiet revolution is reshaping our understanding of probiotics, the beneficial bacteria found in yogurt and fermented food items. Probiotics and microbiome-based interventions are now being explored as powerful allies in immunotherapy, transforming how we treat two of the world’s most formidable health challenges: cancer and diabetes.
Our gut is home to trillions of microbes, collectively known as the microbiome. Think of it as a bustling city where different bacterial neighbourhoods perform specific jobs. Scientists are discovering that these microscopic passengers do far more than just digest fibre. They are the drill sergeants of our immune system, training our internal defences to distinguish between friend and foe, and even shaping how our bodies respond to chronic diseases.
Today, this gut-check is moving from the breakfast table to the cutting edge of medicine. When these good bacteria thrive in our system, they produce microbial metabolites that are not just waste products. They are fuel for our immune cells, helping them stay fit and alert. They interact with immune cells that line the gut, sending chemical signals that ripple throughout the entire body.
In a balanced gut, the immune system is calm but ready to attack invaders. When the balance of gut bacteria is disrupted, however, immune responses can become poorly regulated, becoming either sluggish or excessively aggressive. Over time, this immune imbalance is associated with chronic, low-grade inflammation, a condition linked to diseases such as insulin resistance and cancer.
Making the ‘cold’ tumors ‘hot’
For decades, the ‘Big Three’ of cancer treatment were surgery, radiation, and chemotherapy. Then came immunotherapy, a revolutionary shift that, instead of poisoning the tumor directly, unlocks the body’s own immune system to do the real fight against many different cancers. The most successful of these are ‘checkpoint inhibitors’. Cancer cells are masters of disguise since they use ‘molecular handshakes’ to tell immune cells, particularly T-cells, not to attack. Checkpoint inhibitors break that handshake, allowing T-cells to see the tumor for what it really is.
However, despite its miracle drug power, immunotherapy has a challenging catch: it does not work for everyone. In many cancers, only 20-40 percent of patients experience a benefit, and the majority fall into the non-responder category.
Some tumors start shrinking but then learn to hide again and evolve to become resistant to current drugs. Ramping up the immune system can sometimes lead it to attack healthy organs, leading to autoimmunity. For years, doctors couldn’t explain why two patients with the same cancer, receiving the same drug, had wildly different outcomes.
The answer, it turns out, wasn’t just in their DNA; it was in their gut.
Recent clinical breakthroughs have revealed a startling pattern. Patients who respond well to immunotherapy tend to have a much more diverse and healthy population of gut bacteria. When researchers took stool samples from responders and transplanted them into mice with cancer, the mice suddenly started responding to treatment too. This indicated that the microbiome isn’t just a bystander. It is a functional engine driving the success of modern medicines.
Compared with laboratory mice, humans harbour microbiomes shaped by far more complex life histories.
While cancer therapy focuses on activating the immune system, the fight against diabetes is often about balancing it. Type 1 Diabetes is an autoimmune attack where the body destroys its own insulin-producing cells. Early research suggests that specific probiotics can strengthen the gut barrier, prevent leaky gut and stop the triggers that cause the immune system to misfire in the first place.
Type 2 Diabetes, a chronic inflammation often starting in the gut, leads to insulin resistance. Probiotics, such as Lactobacillus species, have shown promise in clinical trials for reducing systemic inflammation and enhancing the body’s ability to process sugar. By fixing the microbial pool in the gut, we can potentially lower the body’s inflammatory noise, making it easier to manage blood glucose.
The future of immunotherapies: ‘Living pharmacies’
We are moving away from ‘one-size-fits-all’ yogurt towards designer probiotics. The future of medicine likely includes engineered microbes, where scientists are now programming bacteria to travel directly to inflamed sites and release immune-boosting signals on command. For instance, Bifidobacterium species found in many fermented foods have a unique biological superpower. They are anaerobic, meaning they thrive in low-oxygen environments.
Since the centre of a solid tumor is often oxygen-starved, these bacteria naturally home in on tumors like a GPS. Researchers are now using engineered Bifidobacterium as “Trojan Horses” to target tumor cells exclusively, thereby preventing collateral damage to healthy cells. If Bifidobacterium is the navigator, the Lactobacillus species found in our yogurt is the drill sergeant. These strains excel at priming the immune system before the first dose of immunotherapy is even given.
A landmark 2025 meta-analysis showed that Lactobacillus johnsonii can actually increase the stemness of T-cells, meaning their inherent capacity to self-renew. This keeps them from getting exhausted during the long battle against cancer, allowing the immunotherapy to work for much longer periods. One of the biggest immunotherapy killers is the accidental use of antibiotics, which can wipe out a patient’s response to treatment. A recent clinical trial in Non-Small Cell Lung Cancer (NSCLC) demonstrated that a specific cocktail of Lactobacillus and Bifidobacterium could rescue patients who had recently taken antibiotics, restoring their immune diversity and significantly prolonging their overall survival.
The future of immunotherapy may not be just a vial of drugs, but it’s the trillions of microscopic allies living inside us, waiting for the signal to join the fight. We are moving away from generic probiotics toward precisely engineered bacterial strains designed to prime the immune system for battle. By nurturing our gut, we aren’t just helping our digestion; we are arming our personal internal army for the fight of its life.
Jugal Das is a Ramalingaswami Fellow Faculty at Shiv Nadar University.
Soumya Puri is a PhD student at Shiv Nadar University.
Originally published under Creative Commons by 360info™.
