Ozempic Vs Your Gut: Maldigestion and Microbiome Mayhem?

Ozempic (semaglutide), is a GLP-1 receptor agonist approved initially for Type 2 diabetes treatment, which is now conventional medicine’s solution for weight loss. Semaglutide’s meteoric rise is attributed to its powerful appetite-suppressing effects and impressive weight loss results. However, its popularity often overlooks the significant negative implications the drug has on our digestive health. While mainstream medicine touts Ozempic’s metabolic benefits, an integrative medicine perspective demands a critical examination of its impact on our digestion, digestive system, and gut microbiome. In this blog, I will analyze the pharmacological mechanisms of Ozempic, its physiological effects on our digestion, and the unintended consequences that may threaten the long-term gut health of those taking the medication.^{1 2 3}

Ozempic and Your Stomach

Ozempic (semaglutide) effectively mimics the action of glucagon-like peptide-1 (GLP-1), a powerful hormone produced by enteroendocrine L-cells within your distal small intestine and colon in response to eating. GLP-1 is vital for regulating insulin secretion, inhibiting glucagon release, and slowing gastric emptying, all essential for maintaining healthy blood glucose levels. However, while these benefits are crucial for glycemic control, they can also disrupt your body’s natural digestive rhythm known as the migrating motor complex. By artificially enhancing GLP-1 signaling, Ozempic causes gastroparesis, which results in delayed gastric emptying. GLP-1 agonists slow gastric emptying by directly acting on vagal afferent neurons and smooth muscle cells within our stomach, reducing motility and delaying the transit of food into our duodenum.^{4 5 6 7 8}

Our stomach is a muscular organ that churns and acidifies the food we enjoy. To maintain efficient digestion, our stomach needs to empty our digested food, known as chyme, at the right time through our pyloric sphincter into the first part of our small intestine, or duodenum. However, Ozempic directly inhibits gastric motility (gastroparesis), which slows down the emptying process and leads to a longer retention of chyme within our stomach. Gastroparesis leads to sluggish stomach motility, impairing the mechanical breakdown of food and hampering the coordinated release of digestive enzymes and bile acids, ultimately negatively affecting digestion and your overall health. Gastroparesis causes symptoms such as bloating, gas (burping), early fullness, abdominal pain, dyspepsia, reflux, nausea, and vomiting.^{9 10 11 12 13 14}

Ozempic also suppresses gastric acid secretion, which is another effect of GLP-1 agonism. GLP-1 receptor agonists inhibit gastric acid production by modulating vagal efferent signaling and reducing the activity of parietal cells in the gastric mucosa. When GLP-1 receptors are activated within the central nervous system and the gastric mucosa, a decrease in acetylcholine-mediated stimulation of parietal cells occurs, hindering stomach acid production. As a result, our stomach’s output of hydrochloric acid is diminished. Reduced hydrochloric acid secretion can interfere with protein digestion within our stomach and increase our risk of developing or worsening microbial dysbiosis within our upper gastrointestinal tract. Hydrochloric acid is essential for protecting us against ingested pathogens, reducing microbe colonies, vitamin B12 absorption (intrinsic factor), and activating pepsinogen into pepsin, an enzyme necessary for breaking down proteins within our stomach. When less acid is produced, digestion becomes impaired, creating an environment that may foster microbial imbalances. Chyme now sits within our stomach for extended periods, giving microbes more time to utilize it for energy, which can lead to excessive burping and bloating within our upper gut and dysbiosis.^{15 16 6 18 19 20 21}

Taking Ozempic May Cause or Worsen SIBO

Our small intestine is where nutrient absorption occurs, and its function is closely regulated by its motility, enzymatic activity, and our microbiome. Ozempic (semaglutide), which delays gastric emptying, affects the timing of our migrating motor complex and delays stomach chyme entering our duodenum for further digestion. Delayed stomach emptying can disrupt the release of pancreatic enzymes and bile, which are crucial for emulsifying fats, digesting proteins, and absorbing fat-soluble vitamins like vitamin A or D. Bile is also antimicrobial against many microbes, and its proper release into our duodenum can help prevent or help relieve dysbiosis.^{22 23}

Functional medicine practitioners often notice nutrient deficiencies in patients who use GLP-1 agonists, especially when dietary intake is reduced due to appetite suppression. Slowed intestinal transit time may also lead to small intestinal bacterial overgrowth (SIBO), a condition characterized by excessive microbial colonization of our small intestine. SIBO is associated with bloating (usually around our belly button), belching, flatulence, diarrhea, constipation, abdominal pain, abdominal distension, and malabsorption. The underlying causes of SIBO include impaired gastrointestinal motility, reduced gastric acid production, dysbiosis, and altered immune function within our small intestine, all of which can be influenced by Ozempic. Microbes fermenting chyme longer within our small intestine leads to greater microbe colonies, possibly causing dysbiosis, bloating, flatulence, abdominal pain, and abdominal distension.²⁴

Our gut microbiome is a complex ecosystem composed of trillions of microorganisms that play a crucial role in our digestion, immune regulation, and metabolism. The impact of Ozempic on our microbiome is multifaceted and not yet fully understood, but emerging research indicates possible changes in our gut microbiome. Studies suggest that GLP-1 agonists like Ozempic may increase the abundance of Akkermansia muciniphila, a bacterium that breaks down mucin and is associated with improved metabolic profiles. Ozempic usage might benefit those who I have coached with low colony-forming units of Akkermansia muciniphila. However, elevated levels of Akkermansia muciniphila, a Gram-negative bacteria that breaks down mucin (which the mucosal lining of your digestive tract is made from), have been associated with increased gut permeability (leaky gut), intestinal inflammation from increased endotoxins, Th-1 dominance from increased endotoxins, and development of Akkermansia muciniphila hydrogen sulfide producing dysbiosis.²⁵

From a functional medicine perspective, healthy microbial diversity is essential. The appetite-suppressing and food volume-reducing effects of Ozempic can lead to a limited variety of substrates within our intestines available for microbial fermentation. This reduction may decrease the production of short-chain fatty acids (SCFAs) from a reduction of substrates within our intestines, such as butyrate, acetate, and propionate, which are vital to the health of our colon’s mucosal barrier, immune system, and inflammation regulation. Most Americans do not get enough fiber and prebiotics in their diet to feed their microbiome as is, and a reduction in food intake can lead less substrates for our microbes to produce SCFAs. Butyrate, in particular, is crucial for preserving our intestinal tight junction integrity, preventing increased intestinal permeability, which is often called “leaky gut.” A decline in SCFA production may increase the risk of systemic inflammation and immune dysregulation.^{26 27}

However, Ozempic usage could also lead to an increased production of beneficial SCFAs. Ozempic moves your gut’s microbial balance from more Firmicutes to greater colonies of Bacteroidetes (which might worsen dysbiosis for some people if Bacteroidetes levels increase more than twenty-five percent of your total gut microbiome) and increases the abundance of key SCFA producers including Akkermansia muciniphila, Bifidobacteria, Lactobacillus, and Muribaculaceae, bacteria that thrive on fiber and prebiotics and produce short chain fatty acids. Ozempic, by slowing your migrating motor complex and motility, allows fiber and prebiotic digesting bacteria more time to ferment fiber and prebiotics we have ingested within our intestinal tract, increasing overall SCFA production. Ozempic’s effect on SCFA within our gut is a delicate balance.²⁸

The alterations in gastrointestinal motility caused by Ozempic easily can cause small intestinal dysbiosis. Typically, our small intestine houses fewer microbes than our large intestine; however, delayed transit leads to increased fermentation within our small intestine, resulting in a significant rise of microbial colonies. Chronic constipation, caused by slow motility, raises intraluminal pressure within our large intestine, which can compromise the integrity of our ileocecal valve and impair its essential function as a one-way barrier. Our ileocecal valve, a crucial sphincter-like structure located between our small intestine’s ileum and our large intestine’s cecum, regulates the flow of digestive contents and prevents the backflow of large intestinal fecal material back into the ileum of our small intestine. Dysfunction in the ileocecal valve allows colonic bacteria to reflux into our small intestine, leading to microbial dysbiosis and significantly contributing to Small Intestinal Bacterial Overgrowth (SIBO) symptoms. Significant intestinal bacterial migration into our large intestine exacerbates SIBO. Increasing the risk of developing mild to severe endotoxemia, a serious condition in which lipopolysaccharides (LPS) from Gram-negative bacteria, including Akkermansia muciniphila, enter our bloodstream due to a compromised intestinal barrier and trigger our immune system, causing inflammation.^{29 30}

Gastrointestinal Side Effects of Taking GLP-1 Agonists

The gastrointestinal side effects of Ozempic (semaglutide) are well-documented and include nausea, vomiting, diarrhea, constipation, bloating, and abdominal pain. Often dismissed as temporary or related to medication dosage, these symptoms indicate deeper digestive health issues. Nausea and vomiting can suggest impaired gastric motility, microbial dysbiosis, reduced stomach acid production, and problems with central nervous system signaling. Diarrhea may stem from bile acid malabsorption or hydrogen-producing bacterial dysbiosis or acute hydrogen sulfide bacterial dysbiosis. Constipation often results from slowed colonic transit that interferes with our body’s migrating motor complex and can be caused by Archaeal or chronic hydrogen sulfide dysbiosis. Integrative medicine practitioners view these symptoms not as isolated incidents but as signs of a systemic imbalance associated with Ozempic use. The gut-brain axis, the communication network between our enteric and central nervous systems, is particularly sensitive to GLP-1 (glucagon-like peptide-1) changes, which can disrupt our migrating motor complex.^{31 32 33 34 35 36 37}

Ozempic affects satiety and causes nausea by mimicking endogenous incretin hormones that interact with our hypothalamus within our brain to modulate our appetite by enhancing satiety signaling and reducing our body’s hunger cues (like thinking about food, food cravings, growling abdomen (which is our intestines contracting fecal matter moving through our digestive system controlled by our migrating motor complex), and moodiness to name a few). Ozempic also alters our vagal afferent activity, interfering with our migrating motor complex, slowing gastric emptying, triggering nausea, and delaying our gut motility due to heightened vagal tone and enteric nervous system modulation. People suffering from autonomic dysfunction, such as those with postural orthostatic tachycardia syndrome (POTS), may experience more severe symptoms when taking Ozempic. Additionally, appetite suppression and reduced caloric intake can lead to hypoglycemia, fatigue, mood changes, and hormonal imbalances. Key hormones, including leptin, ghrelin, and peptide YY, are all influenced by nutrient status and gut signaling. When these hormones are persistently dysregulated, especially under the influence of Ozempic, our body may struggle to adapt metabolically, increasing the likelihood of compensatory weight gain and reduced hormonal resilience once the drug is withdrawn. Integrative medicine highlights the importance of sustainable lifestyle changes over pharmacological appetite suppression, recognizing that health arises from balanced nutrition, regular physical activity, good gut health, and circadian rhythm entrainment.^{38 39 40 41}

Ozempic affects the health of our pancreas, gallbladder, and liver, which all play crucial roles in proper digestive health and metabolism. As a GLP-1 agonist, Ozempic stimulates insulin secretion and inhibits glucagon release, enhancing glycemic control and, over time, straining our pancreatic beta cells. There have been some reports of pancreatitis linked to semaglutide use, although the specific causation remains uncertain and studies are mixed. Pancreatitis causes sudden, severe upper abdominal pain that may radiate to the back, accompanied by nausea, vomiting, and tenderness. In addition to upper abdominal pain, nausea, and vomiting, pancreatitis can cause fever, rapid heart rate, abdominal distension, and oily or foul-smelling stools due to impaired fat digestion. Severe cases of pancreatitis may also lead to jaundice, dehydration, weight loss, and systemic inflammation. From an integrative medicine perspective, any medication that alters hormone signaling should be used cautiously, especially in individuals with existing pancreatic insufficiency, gallbladder disease, or a history or family history of pancreatitis.^{42 43 44 45}

Our hepatobiliary system is also influenced by GLP-1 modulation. Ozempic may change bile acid metabolism and affect gallbladder motility, potentially increasing the risk of gallstones and biliary dyskinesia. Bile acids are critical for fat digestion and act as signaling molecules regulating microbial composition and metabolic pathways. Disruption of bile flow can result in fat malabsorption, steatorrhea, and dysbiosis. Ozempic has been rarely associated with drug‐induced liver injury and the studies are mixed, usually occurring within the first one to six months of its use and marked by asymptomatic elevations of the liver enzymes aspartate aminotransferase (AST) and alanine transaminase (ALT) or more rarely, clinical hepatitis with jaundice and right upper quadrant discomfort. Recent studies suggest that Ozempic’s modulation of lipid metabolism can induce liver mitochondrial stress and activate inflammasomes, while its effects on bile acid homeostasis may exacerbate hepatocellular inflammation and fibrogenesis. People most susceptible to semaglutide‐induced liver injury often share risk factors such as being over the age of sixty, preexisting hepatic steatosis and/or autoimmune liver disease, alcoholism. Liver health marker blood tests should be taken frequently for those taking Ozempic suffering from liver disease or those who have a family history of liver disease. Early detection of liver subclinical enzyme elevations allows for Ozempic dose adjustment or discontinuation, hopefully preventing progression to clinically significant liver injury.^{46 47 48 49 50 51 52}

Does Fix Your Gut Recommend Ozempic and Can Its Digestive Side Effects Be Hacked?

Ozempic (semaglutide) is a powerful tool in the fight against diabetes and obesity, but its effects on the digestive system require careful examination. The drug can lead to delayed gastric emptying, impaired nutrient absorption, microbial imbalances, and gastrointestinal discomfort, meaning its impact goes beyond appetite suppression. A functional medicine approach focuses on addressing root causes, personalized nutrition, and caring for our microbiome, principles that often conflict with the standard one-size-fits-all model of GLP-1 agonist therapy of conventional medicine.

If someone is considering taking Ozempic, several supplements may help reduce its potential negative impact on the digestive tract and microbiome. One option is to supplement with Betaine HCL, which increases stomach acidity and can enhance digestion and the health of our stomach microbiome. However, it’s important to note that higher stomach acidity might diminish Ozempic’s effectiveness in promoting prolonged feelings of fullness, potentially leading to increased hunger and negating one of the drug’s primary benefits.

Additionally, taking digestive enzymes while on Ozempic could improve the digestion and absorption of food. Since Ozempic may decrease butyrate production within our large intestine, supplementing with butyrate may support the health of the intestinal tract and microbiome. Ingesting targeted prebiotics like 2-FL (if you are not lactose intolerant) and/or acacia fiber might help your microbiome produce adequate amounts of short chain fatty acids and remain healthy. To prevent potential mitochondrial toxicity in the liver caused by Ozempic, taking a hundred to two milligrams of ubiquinol daily with a meal containing dietary fat might be beneficial. If you notice pale stools while taking Ozempic, adding ox bile to meals with dietary fat could enhance fat digestion and absorption, particularly when used alongside Betaine HCL and/or digestive enzymes. However, ox bile should be avoided if you have bile acid malabsorption, gastritis, stomach ulcers, or bile reflux. Taking zinc carnosine may help prevent leaky gut syndrome and imbalances within our upper gut’s microbiome during Ozempic treatment. Lastly, consuming ginger tea or a ginger supplement might alleviate nausea associated with Ozempic.

Ensure you are staying hydrated when taking Ozempic, which might help prevent constipation. Eating up to three meals daily and fasting between meals, only consuming liquids would interrupt your migrating motor complex less and improve motility. Proper magnesium supplementation prevents constipation by drawing more water into your large intestine as an osmotive laxative, softening your stool and making it easier to pass. I also recommend walking for thirty minutes three to four times weekly and, when you defecate, using a Squatty Potty to optimize your digestive motility while on Ozempic. Finally, excessive refined sugar intake (more than twenty to four grams, sometimes less) can feed and exacerbate upper gut dysbiotic flora.

Is your gut health suffering because you took Ozempic?

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