From antibiotics and stress to poor sleep and processed food, everyday habits that seem harmless are gradually damaging an ecosystem of trillions of microorganisms that protects almost every aspect of our health.
Inside your gut lives an ecosystem more complex than you might imagine. Trillions of microorganisms regulate immunity, communicate with the brain, produce vitamins and help keep pathogens under control. This is the gut microbiome, and the modern lifestyle exposes it to multiple threats every day.
Research conducted over the past two decades has revealed links between microbiome health and almost every chronic condition associated with modern life, including diabetes, obesity, depression, autoimmune diseases and inflammatory disorders. [1] It is not an exaggeration to describe this as one of the most important discoveries in modern medicine.
What is particularly concerning, yet rarely discussed, is that most people do not realise their microbiome may be compromised. The symptoms of dysbiosis, an imbalance within the microbiome, are often vague and easily attributed to other causes. They may include chronic fatigue, digestive problems, frequent infections, skin conditions and anxiety.
This article explores the main factors that disrupt the microbiome, with particular attention to medications, a subject that is rarely discussed openly.
What is the gut microbiome and why is it so important?
The gut microbiome consists of approximately 38 trillion microorganisms living in the digestive system, primarily in the large intestine. From a genetic perspective, the microbiome encodes more than three million genes, almost 150 times more than the human genome. [2] The greater the variety of bacterial species present, the more resilient the entire ecosystem tends to be.
The microbiome ferments fibre into short-chain fatty acids, which nourish the intestinal lining and help reduce systemic inflammation. It synthesises vitamins K and B12, trains the immune system and protects against pathogens. [3]
Perhaps the most fascinating discovery of recent years concerns the gut–brain axis, the communication network connecting the digestive system and the brain. Nearly 90% of the body’s serotonin is produced in the gut, under the influence of the microbiome. [4] This helps explain why disruption in the gut may also affect psychological wellbeing.
| 38 bil. microorganisms in the adult human gut | 1000+ different bacterial species in a healthy microbiome | 70% of the immune system is located within the intestinal mucosa | 90% of serotonin is produced in the gut |
Key facts about the gut microbiome. Sender et al., PLoS Biol, 2016; Cryan et al., Physiol Rev, 2019.
Ultra-processed food: the most extensively studied microbiome disruptor
Food is one of the most powerful tools for shaping the microbiome, both positively and negatively. A Harvard study showed that the microbiome begins to change significantly within just 24 to 48 hours of a dietary change. [5]
The modern dietary pattern is high in refined carbohydrates, industrial sugars and additives, while being low in fibre and fermented foods. This selectively deprives beneficial microorganisms, including Lactobacillus and Bifidobacterium species, of the nutrients they need.
Emulsifiers are particularly concerning. The food industry routinely adds substances such as polysorbate 80, carrageenan and carboxymethylcellulose to processed foods to improve texture. A study published in Nature in 2015 showed that these additives may disrupt the protective layer of the intestinal lining and promote chronic inflammation. [6]
Artificial sweeteners, once considered metabolically harmless, may also have undesirable effects. Research published in Cell in 2022 documented that sweeteners such as saccharin and sucralose can selectively alter bacterial groups involved in carbohydrate metabolism. In some participants, this paradoxically worsened glucose tolerance through changes in the microbiome. [7]
Researchers at Stanford University discovered another concerning effect. Children whose parents consume diets low in fibre may inherit a less diverse microbiome, and some bacterial species may not return even after fibre is reintroduced. [8]
A comparison with hunter-gatherer communities such as the Hadza of Tanzania provides an illuminating contrast. Their microbiomes are around 40% more diverse than those of Western populations. Researchers attribute this partly to a diet rich in varied plant fibres and fermented foods. [9]
Microbiome diversity depends directly on the diversity of food on the plate. A monotonous diet, even when it is considered healthy, encourages a less diverse microbiome.
Chronic stress: a psychological attack on the gut ecosystem
The gut–brain axis is not a metaphor. It is a genuine two-way communication network operating through the vagus nerve, the autonomic nervous system and immune signalling.
During chronic stress, elevated cortisol levels may alter intestinal permeability, reduce the production of protective IgA antibodies and directly change the bacterial composition of the microbiome in ways that favour potentially harmful microorganisms. [10]
A meta-analysis of 34 controlled studies concluded that psychological stress consistently reduces levels of Lactobacillus and Bifidobacterium, two bacterial groups closely associated with mental health and immune function. [11]
A study involving medical students during an examination period reported similar findings. Microbiome diversity declined significantly, while inflammatory markers increased.
What makes this problem particularly difficult is that microbiome changes may then intensify anxiety and depression, creating a self-reinforcing cycle that can be difficult to interrupt. Research published in Nature Microbiology, involving more than one thousand participants, found that lower levels of Coprococcus and Dialister bacteria were consistently associated with depression, regardless of antidepressant treatment. [12]
Disrupted sleep: a circadian rhythm the microbiome cannot afford to lose
Few people realise that gut bacteria have their own circadian rhythms, synchronised with our sleep and wake cycles.
A study published in Cell in 2014 observed mice exposed to artificial jet lag and documented significant changes in microbiome composition. These included increases in Firmicutes species associated with obesity and metabolic changes resembling diabetes. Just two days of disrupted sleep were sufficient to produce measurable changes. [13]
Research involving shift workers found that they had significantly lower microbiome diversity, higher levels of Proteobacteria, a group that includes many potentially pathogenic organisms, and lower production of butyrate, which nourishes the intestinal lining. [14]
A University of Pittsburgh study followed participants whose sleep was restricted to five hours per night. Microbiome diversity declined after only one week, while inflammatory markers increased at the same time. [15]
The recommendation to sleep for seven to nine hours is not arbitrary. It is a biological requirement of the microbiome as well as the brain.
Excessive hygiene: a paradox that affects the immune system
The hygiene hypothesis was proposed by epidemiologist David Strachan in 1989 and has since been supported by numerous studies. It suggests that the rise in autoimmune and allergic diseases in developed countries may partly result from reduced exposure to microorganisms that are important for training the immune system. [16]
Antibacterial soaps, disinfectants and antiseptics eliminate not only pathogens but also harmless and potentially beneficial microorganisms.
In 2016, the US Food and Drug Administration banned 19 chemicals from over-the-counter antibacterial soaps, including triclosan. These substances had not been shown to be more effective than ordinary soap and water, while raising concerns about antimicrobial resistance and effects on microbial ecosystems. [17]
One of the most frequently overlooked topics in perinatal medicine is the influence of delivery method on the infant microbiome. Babies born by caesarean section do not undergo the same exposure to maternal vaginal microorganisms, including Lactobacillus and Bifidobacterium. Their initial microbiome may therefore resemble skin and environmental microorganisms more closely.
A seven-year follow-up study found higher rates of asthma, obesity and type 1 diabetes among children born by caesarean section. Researchers believe that differences in early microbial colonisation may be one contributing factor, although many other influences are also involved. [18]
Physical inactivity: an often-overlooked factor
A study comparing 40 professional rugby players with 46 sedentary participants found that the athletes had significantly greater microbiome diversity. They also had higher levels of Akkermansia muciniphila, a bacterium associated with intestinal barrier function, and Faecalibacterium prausnitzii, an important producer of butyrate.
A particularly interesting finding was that microbiome differences were even more pronounced than dietary differences, suggesting that physical activity itself may have a direct effect. [19]
A randomised controlled trial followed 32 sedentary participants through a six-week aerobic exercise programme. Microbiome diversity increased significantly, particularly levels of Bifidobacterium and Lactobacillus species.
When participants stopped exercising, their microbiomes returned towards baseline within two weeks. [20] The benefit therefore appears to depend on continued physical activity, which is both encouraging and cautionary.
Medications and the microbiome: a serious threat that is rarely discussed
Among all the factors capable of disrupting the gut microbiome, medications can have some of the strongest and longest-lasting effects. Yet this subject is rarely discussed openly.
A study published in Nature in 2018 analysed the effects of 1,079 different medications on 40 bacterial species. It found that almost 25% of the tested medicines significantly inhibited the growth of at least one bacterial species, including many drugs that had never been classified as antibiotics. [21]
Antibiotics
Antibiotics are among the greatest achievements of modern medicine, but they are also some of the most powerful known disruptors of the microbiome.
A study published in Nature Microbiology in 2018 followed 12 healthy participants who received a short course of three antibiotics. Microbiome diversity declined by between 50% and 90%, and some bacterial species disappeared without evidence of recovery even after 12 months. [22]
A review of 17 longitudinal studies concluded that a single course of antibiotics may permanently eliminate between 3% and 10% of bacterial species. Recovery also tends to become slower with age. [23]
One direct consequence of antibiotic-induced dysbiosis is infection with Clostridioides difficile, an opportunistic pathogen responsible for an estimated 15,000 to 30,000 deaths each year in the United States. [24]
Proton pump inhibitors
Omeprazole, pantoprazole and similar proton pump inhibitors are among the most commonly prescribed medications in the world. In some countries, up to 10% of adults use them regularly.
By substantially reducing stomach acid, these medicines may allow bacteria from the upper digestive tract to survive and colonise areas where they would not normally be present. This can contribute to small intestinal bacterial overgrowth, commonly known as SIBO. [25]
A study involving almost 1,815 proton pump inhibitor users documented significantly higher levels of oral bacteria in the gut, increased levels of potentially harmful microorganisms and lower microbiome diversity. The effects were associated with the duration and dose of treatment. [26]
A study published in JAMA Internal Medicine also reported an association between long-term proton pump inhibitor use and an increased risk of dementia. Researchers suggested that changes in the gut–brain axis might be one possible explanation. However, this finding remains controversial, and later research has not established a clear causal relationship. [27]
Non-steroidal anti-inflammatory drugs
Non-steroidal anti-inflammatory drugs, or NSAIDs, include ibuprofen, acetylsalicylic acid and diclofenac. It is estimated that approximately 30 million doses of NSAIDs are taken globally every day.
In addition to directly irritating the intestinal lining, NSAIDs may also alter the microbiome. Research involving 150 healthy participants taking standard doses of ibuprofen for four weeks found a statistically significant reduction in microbiome diversity, lower levels of butyrate-producing bacteria and an increase in Proteobacteria. [28]
Some changes remained present four weeks after treatment had ended.
Metformin and antidepressants
Metformin, the standard first-line treatment for type 2 diabetes, appears to have a complex relationship with the microbiome. It increases levels of the potentially beneficial bacterium Akkermansia muciniphila, while also reducing certain Lactobacillus species.
Some of metformin’s therapeutic effects may occur through microbiome changes. This means that individuals with substantial dysbiosis could theoretically respond differently to treatment. [29]
Selective serotonin reuptake inhibitor antidepressants are also being increasingly studied. An in vitro study found that fluoxetine directly inhibited the growth of certain Lactobacillus strains, bacteria involved in pathways connected with serotonin production.
This raises an interesting question: a medication used to treat depression may also affect microorganisms involved in mood regulation. However, the evidence is still preliminary, and treatment decisions should always be made together with a doctor. [30]
The key conclusion is not that medically necessary medicines should be avoided. Antibiotics save lives, proton pump inhibitors can provide essential protection, and NSAIDs reduce pain and inflammation.
The important point is that informed patients and healthcare professionals should consider possible effects on the microbiome and take appropriate steps to support recovery when needed.
How to protect and restore the microbiome: what does the science say?
The good news is that the microbiome is highly adaptable. Measurable changes may occur within 48 to 72 hours when appropriate interventions are introduced.
One of the strongest dietary strategies supported by research is consuming 30 or more different plant foods each week. Data from the American Gut Project, involving more than 10,000 participants, showed that people reaching this threshold had substantially greater microbiome diversity. [31]
A Stanford study published in 2021 found that fermented foods such as kefir, sauerkraut, kimchi and kombucha not only introduce live microbial cultures but may also reduce markers of systemic inflammation. [5]
The effects of probiotic supplementation vary depending on the specific strains, dose and condition being treated. Strains with relatively strong evidence for particular indications include Lactobacillus rhamnosus GG, Bifidobacterium longum BB536 and Saccharomyces boulardii.
Probiotics may be particularly relevant during antibiotic treatment. A study involving 2,941 patients found that concurrent probiotic use reduced the occurrence of antibiotic-associated diarrhoea by 42% and supported the recovery of microbiome diversity. [32]
For severe cases of dysbiosis, particularly recurrent C. difficile infection, faecal microbiota transplantation has shown cure rates of around 80% to 92%, compared with substantially lower success rates for repeated antibiotic treatment alone. [33]
Signs of dysbiosis: when the microbiome may need support
- Persistent digestive problems
Bloating, excessive gas, diarrhoea or constipation lasting for several weeks. - Increased food sensitivity
New food intolerances or frequent allergic reactions without an obvious cause. - Frequent respiratory infections
Repeated infections or a perceived decline in immune resilience, occurring more than three or four times per year. - Persistent fatigue and other systemic symptoms
Chronic exhaustion, skin problems such as eczema, acne or psoriasis, or unexplained changes in mood.
These symptoms may have many other causes. Persistent or severe symptoms should therefore be assessed by a qualified healthcare professional.
Strategies for restoring the microbiome: an overview of the evidence
- Consume at least 30 different plant foods each week
One of the strongest dietary approaches for encouraging microbiome diversity - Include fermented foods regularly
Examples include kefir, sauerkraut, kimchi and kombucha. - During antibiotic treatment, ask your doctor about probiotics
For some people and certain products, probiotics may reduce the risk of antibiotic-associated diarrhoea. - Review proton pump inhibitor treatment lasting longer than eight weeks
Discuss with your doctor whether continued treatment is necessary. Do not stop prescribed medication without medical guidance - Complete at least 150 minutes of moderate aerobic activity each week
Regular movement may support microbiome diversity and metabolic health. - Sleep for seven to nine hours and actively manage chronic stress
Sleep and stress regulation support both gut and immune function.
The gut microbiome is not a passive passenger within the body. It is an active, sensitive ecosystem that responds to everyday decisions, including what you eat, how you sleep, how much stress you experience and which medications you take.
Understanding these relationships is not an obscure medical interest. It is part of the foundation of everyday health.
Scientific references
[1] Turnbaugh PJ et al. The human microbiome project. Nature. 2007;449:804–810.
[2] Qin J et al. A human gut microbial gene catalogue. Nature. 2010;464:59–65.
[3] Rowland I et al. Gut microbiota functions: metabolism of nutrients. Eur J Nutr. 2018;57(1):1–24.
[4] Yano JM et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015;161(2):264–276.
[5] Wastyk HC et al. Gut-microbiota-targeted diets modulate human immune status. Cell. 2021;184(16):4137–4153.
[6] Chassaing B et al. Dietary emulsifiers impact the mouse gut microbiota. Nature. 2015;519:92–96.
[7] Suez J et al. Personalized microbiome-modulated responses to dietary interventions. Cell. 2022;185(18):3307–3328.
[8] Sonnenburg ED et al. Diet-induced alterations in gut microflora. Cell Host Microbe. 2016;19(3):334–348.
[9] Smits SA et al. Seasonal cycling in the gut microbiome of the Hadza hunter-gatherers. Science. 2017;357(6353):802–806.
[10] Bailey MT et al. Exposure to a social stressor alters the structure of the intestinal microbiota. Brain Behav Immun. 2011;25(3):397–407.
[11] Simpson CA et al. The gut microbiota in anxiety and depression. Neurosci Biobehav Rev. 2021;116:223–244.
[12] Valles-Colomer M et al. The neuroactive potential of the human gut microbiota in quality of life and depression. Nat Microbiol. 2019;4:623–632.
[13] Thaiss CA et al. Transkingdom control of microbiota diurnal oscillations. Cell. 2014;159(3):514–529.
[14] Voigt RM et al. Gut microbiota in workers experiencing job stress. J Occup Environ Med. 2020;62(12):979–985.
[15] Benedict C et al. Gut microbiota and glucometabolic alterations in response to recurrent partial sleep deprivation. Mol Metab. 2016;5(12):1175–1186.
[16] Strachan DP. Hay fever, hygiene, and household size. BMJ. 1989;299(6710):1259–1260.
[17] FDA. Safety and Effectiveness of Consumer Antiseptics. Federal Register. 2016;81(172):61106–61130.
[18] Blustein J et al. Association of caesarean delivery with child adiposity. Int J Obes. 2013;37(7):900–906.
[19] Clarke SF et al. Exercise and associated dietary extremes impact on gut microbial diversity. Gut. 2014;63(12):1913–1920.
[20] Allen JM et al. Exercise Alters Gut Microbiota Composition and Function. Med Sci Sports Exerc. 2018;50(4):747–757.
[21] Maier L et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature. 2018;555:623–628.
[22] Palleja A et al. Recovery of gut microbiota of healthy adults following antibiotic exposure. Nat Microbiol. 2018;3:1255–1265.
[23] Ramirez J et al. Antibiotics as Major Disruptors of Gut Microbiota. Front Cell Infect Microbiol. 2020;10:572912.
[24] CDC. Clostridioides difficile Infection. Centers for Disease Control and Prevention; 2023.
[25] Lombardo L et al. Increased incidence of SIBO during proton pump inhibitor therapy. Dig Dis Sci. 2010;55(5):1331–1336.
[26] Imhann F et al. Proton pump inhibitors affect the gut microbiome. Gut. 2016;65(5):740–748.
[27] Gomm W et al. Association of Proton Pump Inhibitors With Risk of Dementia. JAMA Intern Med. 2016;176(2):171–179.
[28] Rogers MAM, Aronoff DM. The influence of NSAIDs on the gut microbiome. Clin Microbiol Infect. 2016;22(2):178.
[29] Forslund K et al. Disentangling type 2 diabetes and metformin treatment signatures. Nature. 2015;528:262–266.
[30] Macedo D et al. Antidepressants, antimicrobials or both? Eur Neuropsychopharmacol. 2017;27(10):1016–1032.
[31] McDonald D et al. American Gut: an Open Platform for Citizen Science Microbiome Research. mSystems. 2018;3(3):e00031–18.
[32] Johnston BC et al. Probiotics for the prevention of C. difficile-associated diarrhea. Ann Intern Med. 2012;157(12):878–888.
[33] Paramsothy S et al. Multidonor intensive faecal microbiota transplantation. Lancet. 2017;389(10075):1218–1228.
