GLP-1 GUIDE: What's the Difference Between a Probiotic vs Digestive Enzyme?

If you’re on a GLP-1 medication like semaglutide or tirzepatide, chances are your stomach has some thoughts about it. Maybe it’s the sudden nausea, the infamous "sulfur burps," or that weirdly full feeling after just a few bites.

As more people turn to these meds for weight loss or blood sugar control, a new question is popping up: can probiotics or digestive enzymes help with the GLP-1 side effects?

These are all questions I asked before I started taking Zepbound in January 2026. Let’s unpack the difference between a probiotic and a digestive enzyme, how each may help with GLP-1 side effects, and whether it’s worth adding one—or both—to your routine.

How GLP-1s Like Semaglutide and Tirzepatide Affect Digestion

GLP-1 medications work by mimicking a natural hormone that slows digestion, reduces appetite, and improves blood sugar control. The slowdown in gastric emptying is part of what helps you feel fuller faster—but it can also throw your gut for a loop.

Food hangs out in the stomach longer than usual, which can cause bloating, reflux, and nausea. As digestion slows, so does movement through the intestines. For some, that leads to constipation. Others experience diarrhea. Some of us get both within the week before injections.

These side effects are more like when starting the medication, increasing the dose, or eating large meals. Gas, burping, and irregular bowel habits are common side effects, not because something’s “wrong,” but because your body is adjusting to a new pace.

This shift in gut motility and microbial balance is exactly why many turn to digestive enzymes or probiotics for support.

WHAT CAUSES "SULFUR BURPS"?: It’s a burp that smells (and tastes) like rotten eggs, caused by hydrogen sulfide gas in your stomach. These can happen when food sits too long in your gut or from certain bacteria breaking down sulfur-rich foods.

What Is a Probiotic—and Can It Help With GLP-1 Side Effects?

A probiotic is a supplement (or food) that contains live beneficial bacteria meant to support the health of your gut microbiome. Think of it like repopulating your digestive system with good roommates who keep everything running smoothly.

Most of us have trillions of bacteria living in our intestines already, but medications—especially those that slow down digestion, like GLP-1s—can throw off the balance. When food sits in the stomach or intestines longer than it should, it creates a breeding ground for gas, fermentation, and general GI chaos.

Probiotics can help:

Reduce bloating by balancing bacteria that produce gas
Support regular bowel movements, especially if constipation is an issue
Calm diarrhea by reinforcing the gut lining
Improve gut motility (how fast things move through your system)
Support immune health, which is often gut-related

In other words, probiotics work more like long-term gut maintenance. They don’t "fix" things instantly, but consistent use can lead to noticeable changes over a few weeks. Look for strains like Lactobacillus acidophilus, Bifidobacterium longum, or Saccharomyces boulardii (a probiotic yeast that’s great for diarrhea and gas).

What Is the Difference Between a Prebiotic, Probiotic, and Postbiotic?

Probiotics are the actual beneficial bacteria (like Lactobacillus or Bifidobacterium) that help keep your gut microbiome balanced. You get them from supplements or fermented foods like yogurt, kefir, kimchi, and sauerkraut. They help with digestion, immune support, and keeping harmful bacteria in check.

Prebiotics are non-digestible fibers (like inulin, fructooligosaccharides, and resistant starches) that feed the good bacteria already in your gut. They come from foods like onions, garlic, bananas, oats, and asparagus. Think of them as fertilizer for your internal garden.

Postbiotics are what your gut bacteria produce after they eat prebiotics and do their job. These byproducts—like short-chain fatty acids or peptides—help lower inflammation, support your immune system, and keep your gut lining strong. Some supplements include postbiotics directly, especially for people who can’t tolerate live probiotics.

Ideally, your probiotic would include a prebiotic, too. That combo is called a synbiotic, and it gives the good bacteria (probiotics) what they need to survive and thrive (prebiotic). It’s like planting seeds and giving them water. Some advanced synbiotics may include postbiotics, too.

What Is a Digestive Enzyme—and Why Would You Need One on a GLP-1?

Digestive enzymes are different. These are proteins your body produces naturally in your mouth, pancreas, and intestines to help break down food into smaller, absorbable parts. There are different types for different macronutrients—amylase for carbs, protease for protein, lipase for fat, etc.

GLP-1s like Ozempic slow gastric emptying. That means food hangs out in your stomach longer, and digestion gets sluggish. This can lead to a heavy, overly full feeling, burping, reflux, or just plain discomfort—even if you didn’t eat much.

A digestive enzyme supplement can give your system a boost by helping to break down food faster and more efficiently, especially when your stomach is moving in slow motion.

Digestive enzymes can help:

Reduce feelings of fullness and pressure after eating
Ease the breakdown of protein and fat (especially helpful on high-protein diets common with GLP-1 users)
Minimize gas and bloating
Decrease reflux by reducing the volume and acidity of what's sitting in your stomach

Unlike probiotics, which need time to shift your gut balance, digestive enzymes offer support on the spot. They’re best used with food, especially heavier meals or ones with more fat and protein.

Digestive Enzyme vs Probiotic: What’s the Difference?

When considering a digestive enzyme vs. probiotic, it's important to note that they're not interchangeable—but they are complementary. Think of probiotics as the long game for gut health and digestive enzymes as the mealtime support crew.

Both can help ease the digestive side effects many people experience on GLP-1 medications.

Here’s a side-by-side breakdown to keep it simple:

Category	Probiotic	Digestive Enzyme
Function	Supports long-term gut health by restoring bacterial balance	Helps break down food during digestion
When to Use	Daily, ideally with meals or on an empty stomach (varies by strain)	With meals that are harder to digest
Speed of Relief	Gradual—can take days to weeks to feel effects	Immediate—works during the meal
Form	Capsules, powders, or fermented foods like yogurt or kimchi	Pills or chewables taken with food
Best For	Constipation, diarrhea, gas from bacterial imbalance (dysbiosis)	Fullness, sluggish digestion, reflux, or difficulty breaking down foods

Both can be useful, especially if you’re dealing with GLP-1-related discomfort. However, you can't consider one or both to be a GLP-1 side effect destroyer.

Before picking a probiotic vs digestive enzyme, keep a food journal that includes what you ate and the side effects experienced over the next one to 24 hours. I quickly learned that a particular brand of cheese square crackers was leading to uncomfortable side effects.

So, Do You Really Need a Probiotic and a Digestive Enzyme?

Not always—but maybe. Think of it like this: if your digestion feels slow, heavy, or overly full after meals, a digestive enzyme could be a game-changer. If your gut just feels off—you’re bloated often, gassy, irregular, or experiencing the up-and-down cycle of constipation and diarrhea—a probiotic might be more helpful.

But a lot of people on GLP-1s deal with both: food isn’t digesting efficiently and their gut microbiome is out of sync. That’s when a combo approach makes sense.

Here’s how it could work:

Take a digestive enzyme with your largest meal of the day, especially if it’s protein- or fat-heavy.
Take a daily probiotic with breakfast or before bed—something that supports gut flora and digestion long-term.

As always, quality matters. Not all probiotics or enzymes are created equal.

In a report produced by Johns Hopkins Medicine, Morgan Denhard, a registered dietitian, said, "Overall, a healthy person really doesn’t need to take digestive enzyme supplements. The best digestive enzymes are the ones our bodies make naturally, and they work best when you eat a whole food diet.”

However, I certainly wouldn't consider myself an "overall healthy person" since I needed to start taking Zepbound to battle obesity, obstructive sleep apnea, kidney disease, and inflammation.

Are Probiotics and Digestive Enzymes FDA Regulated?

Like most over-the-counter supplements, probiotics and digestive enzymes are not FDA-approved.

The only exceptions are prescription digestive enzymes, like Creaon or Zenpep, for pancreatic insufficiency. These are FDA-approved drugs, but they’re different from over-the-counter enzyme blends marketed for general digestion.

That's why it's important to talk to a nutrition counselor and your healthcare provider to see if these supplements are a good fit for you.

While I can say that I started a probiotic the week before my first Zepbound dose, and I've had minimal side effects, I can't say that the two are related. All of my eating habits changed, from smaller portions to healthier options during meals and snacks.

We've also put together this list of supplements GLP-1 users should consider. That includes collagen, B6, vitamin C, and protein.

How to Choose a Digestive Enzyme or Probiotic

Since most probiotics and digestive enzymes aren’t FDA-approved, third-party testing is your best quality filter. Look for certifications from trusted labs like NSF, USP, or Informed Choice. These seals mean an independent lab verified the product contains what it claims, is free from contaminants, and doesn’t sneak in unlisted ingredients.

NSF is especially respected in both the wellness and athletic world. You can also ask the company for a Certificate of Analysis (COA), which shows lab results for purity and potency.

Avoid products with vague “proprietary blends” or no listed strains or enzyme types. Reputable brands are transparent—about sourcing, strain specificity (for probiotics), and dosing.

Finally, check the label for expiration dates and storage instructions; live bacteria can degrade if handled poorly.

What Are Other Options for GLP-1 Side Effects?

In addition to probiotics and digestive enzymes, other gut-supportive products are emerging to help people manage the GI side effects of GLP-1 medications.

Relesium

One gaining traction in the medical community is Relesium, developed by PanTheryx.

It’s not a probiotic or enzyme but a blend of bovine colostrum and antibody-rich egg powder aimed at reducing inflammation, supporting the gut lining, and restoring microbiome balance.

Dr. Harry Oken, former Chair of the Department of Medicine at Johns Hopkins Howard County Medical Center, strongly supports Relesium.

“Relesium is a game changer for individuals taking GLP-1 medications and experiencing gastrointestinal issues. It’s the first product to market with proven science specifically designed to target GI distress that many patients experience.” - Dr. Harry Oken, Internist

Dr. Oken added, "Relesium is unlike any other gut health product on the market. It is not a probiotic or digestive enzyme. It utilizes all-natural ingredients provided by mother nature, is efficacious, and fast acting in providing relief.”

Water Matters on a GLP-1 Diet

I lived in the deserts of Arizona and Nevada for about 15 years. That helped me develop a great habit of drinking plenty of water. Even with that, I still find myself not being thirsty while taking Zepbound.

Hydration is crucial on GLP-1s because the medication can dull thirst signals, making it easy to under-drink without realizing it. This can worsen constipation, nausea, and fatigue.

Aim for around 64 ounces of water daily, more if you're active. Add electrolytes through sugar-free options like LMNT or Nuun to support hydration without triggering bloating or GI upset.

Sip consistently throughout the day instead of chugging large amounts at once.

Rubbing Alcohol

Keeping a few of the alcohol pads from your GLP-1 injections on hand can be surprisingly useful. If nausea hits, a quick sniff of an alcohol pad can help settle your stomach in a pinch. It’s a simple, portable trick that’s even used in clinical settings for short-term relief.

Other options for relief include:

Ginger: Ginger tea, ginger chews, or capsules have anti-nausea properties backed by research (common in pregnancy and chemo support).
Peppermint: Peppermint tea or essential oil (inhaled or applied topically) can relax stomach muscles and reduce queasiness.
Meclizine: Works by blocking signals in the brain that trigger nausea and vomiting. It’s especially good if your nausea is tied to dizziness, lightheadedness, or that woozy, off-balance feeling.
Avoid lying down right after eating: Helps reduce reflux and nausea.

Digestive Enzymes vs Probiotics Summary

GLP-1 medications like Ozempic and Zepbound are powerful tools—but they also come with digestive side effects that can throw off your routine. While supplements like probiotics and digestive enzymes can help, nothing replaces the power of consistent, balanced, whole-food nutrition.

For those looking to go beyond trial and error, Ashley Legg of Legg Day Fitness offers a one-on-one nutritional accountability program designed specifically for GLP-1 users. Her approach combines real food, expert guidance, and lifestyle coaching that supports long-term success—without sacrificing your comfort or goals.

If you’re ready to get serious about results, she’s waiting to guide you.