July 22, 2026

Small Intestinal Bacterial Overgrowth (SIBO) – Symptoms, Subtypes, and Treatment The purpose of this article is to provide an up-to-date review of SIBO, including symptom patterns, predisposing risk factors, prevalence, specialized diagnostic testing, and potential therapeutic interventions. What is SIBO? Small intestinal bacterial overgrowth (SIBO) is characterized by the presence of an abnormal number of bacteria in the small intestine together with a constellation of GI symptoms. The primary cause of SIBO is identified as increased permeability to lipopolysaccharides (LPSs), which trigger an inflammatory response and lead to chronic inflammation (28). However, it is important to remember that SIBO is just the tip of the iceberg—a dysfunction of many organs and a variety of diseases may contribute to excessive bacterial overgrowth and lead to SIBO (29). SIBO is characterized by increased colonization of anaerobic and aerobic microorganisms within the small intestine, predominantly Gram-negative species including Klebsiella pneumoniae, Escherichia coli, Streptococcus gramineus, Prevotella, Clostridium spp, and Methanobrevibactersmithii (30).  Common gastrointestinal symptoms like abdominal pain, nausea, bloating, gas, diarrhea and/or constipation are considered the typical symptoms of dysbiosis, and consequently of SIBO as well (31). Moreover, these issues can result in malabsorption, leading to nutritional deficiencies (vitamin A, D, E, B12), hypoproteinemia, anemia and weight loss (32,33,34). While SIBO is not a life-threatening condition, it can worsen the patient’s health, and underlying comorbidities (35,36,37,38), leading to decreased quality of life. The gut microbiota serves as an incredible reservoir of microorganisms. Variations in the composition of the gut microbiota occur depending on the particular anatomical area being examined (39). These differences are chiefly influenced by factors like pH level and concentrations of oxygen. The greatest bacterial colonization occurs predominantly in the large intestine (40).  The small intestine, under normal physiological conditions, is colonized by a specific number of microorganisms, from 104–5 CFU/mL in the proximal region to 107–8 CFU/mL in the distal part (41). However, when the host’s defense mechanisms are compromised (such as, gastric acid, MMCs, the ileocecal valve, secretory IgA, and pancreatic enzymes), bacterial translocation and overgrowth can occur in the small or large intestine (42,43,44).  Small intestinal bacterial overgrowth (SIBO) and intestinal methanogen overgrowth (IMO) are two types of gut microbiota disruption (46). The overgrowth of bacteria in SIBO and IMO can be associated with the migration of bacteria from the upper aerodigestive tract or from the colon (47). Subtypes of SIBO Based on the predominant stool pattern and symptoms, IBS is divided into 4 main subtypes: Constipation-predominant (IBS-C or IMO), Diarrhea-predominant (IBS-D or SIBO), Mixed Constipation and Diarrhea (IBS-M), and Hydrogen Sulphide dominant.  Hydrogen Dominant – Increased hydrogen gas (H2) on the breath test is linked to more symptoms of diarrhea (IBS-D) and is categorized as SIBO. It corelates with higher levels of Enterobacteriaceae domain (20). Methane Dominant – Increased methane gas (CH4) on the breath test is associated with symptoms of constipation (IBS-C) and is now categorized as IMO (Intestinal Methanogen overgrowth). It correlates with increased predominance of methanogens, including Methanobrevibacter smithii, as well as Methanosphaera stadtmanae and Methanomassiliicoccus luminyensis (20). Methanogens are not bacteria but are archaea, a third domain of life which lack cell nuclei and have distinct cell wall structures when compared with the other 2 domains, bacteria and eukarya (21). Within the gut, most methanogens are hydrogenotrophic, i.e., they use H2 generated by syntrophic bacterial species for the generation of methane (22). Interestingly, methane (CH4) is directly linked to slowing of intestinal transit in methane-producing IBS subjects (23) and may cause constipation (24). 3.Hydrogen and Methane Dominant (Mixed type) – Hydrogen–methane-dominant SIBO (H+/M+) presents with diverse symptoms ranging from abdominal pain, reflux, and stomach discomfort to fatigue (20). Mixed-type SIBO occurs when the small intestine has an overgrowth of bacteria that produce both hydrogen and methane gases. Because hydrogen-producers fuel methane-producers, the two often coexist. This causes fluctuating, mixed symptoms like alternating diarrhea and constipation, along with severe bloating (20).  The findings by MJ et al. (20) suggest that increases in M. smithii and in bacterial H2S producers including Fusobacterium and Desulfovibrio species may contribute to the predominant constipation and diarrheal subtypes in IBS subjects, respectively; because both methane producers and H2S producing bacteria compete for hydrogen as their source of survival. 4.Hydrogen Sulphide Dominant – Hydrogen–sulfide-dominant SIBO (S+) is characterized by intense gas production in the small intestine that smells like rotten eggs. Increased H2S gas on a breath test is linked to increased prevalence of H2S producers, including Fusobacterium and Desulfovibrio species and corelates with symptoms of diarrhea (20). Increased levels of sulfate-reducing bacteria (which produce H2S) have been linked to colorectal cancer and ulcerative colitis (25,26), which is associated with persistent diarrhea (27). Symptoms of SIBO Symptoms of SIBO are nonspecific and include (1): Abdominal pain Belching Bloating Gas Diarrhea/constipation Abdominal distension Flatulence And indigestion  The symptoms can overlap and vary in frequency, duration, and severity. Typically, over two-thirds of patients report the aforementioned symptoms (1). Conditions that predispose you to SIBO (Causes) (1) Achlorhydria or hypochlorhydria (No or low stomach acid due to chronic gastritis and long-term PPI use) Exocrine pancreatic insufficiency (absence of proteolytic enzymes, abnormal chyme in the small intestine lumen, motility disorders, administration of painkillers and ongoing alcohol consumption) Immunodeficiency syndromes (IgA deficiency, common variable immunodeficiency, AIDS and others) Small intestinal obstruction and stagnation (strictures, adhesions, tumors of the small bowel, Large and/or multiple duodenal and jejunal diverticula) Previous abdominal surgery (afferent loop syndrome after Billroth-II gastric resection, Roux-en-Y stasis syndrome, bariatric bypass surgery) Small intestinal pseudo-obstruction (due to endogenous ethanol production) and some neurological diseases (e.g. myotonic dystrophy, Parkinson disease, Chagasic enteropathy) Irritable bowel syndrome (IBS) – (with motor disturbance, visceral afferent hypersensitivity, psycho-social dysfunction) in which motility disorders enable “secondary” bacterial overgrowth Coeliac disease (The prevalence of SIBO is high, especially in patients who do not respond to a gluten-free diet and/or have lactose intolerance) Crohn’s disease (due to previous ileo-cecal resection and/or large entero-enteric and entero-colic fistulae) Short Bowel Syndrome (The loss of the ileo-cecal valve and the loss of the ileal break from resection of the distal small bowel would accelerate the transit of chyme throughout the entire gastrointestinal tract. Undigested food becomes a substrate for bacterial

A link between SIBO, Probiotics and Metabolic Acidosis Lactic acid is typically produced in excess at a rate of about 20 mmol/kg per day and enters the bloodstream, where it is primarily metabolized by the liver and kidneys. While some tissues can use lactate as a substrate and oxidize it to carbon dioxide (CO2) and water, only the liver and kidneys possess the necessary enzymes for gluconeogenesis from lactate. The tissues that typically produce excess lactic acid include the skin, red blood cells, brain tissue, muscles, and the gastrointestinal tract. During intense exercise, skeletal muscles are the primary source of elevated circulating lactate, which usually returns to normal levels if hepatic metabolism is unimpaired. Elevated lactate levels may result from increased production, decreased clearance, or a combination of both (2). SIBO and D-Lactic Acidosis D-lactic acidosis is an underrecognized complication that can occur in patients with small intestinal bacterial overgrowth, or SIBO, and dysbiosis of the gut microbiome (1). Abdominal bloating, gas and distension are common gastrointestinal symptoms that are caused by many conditions including carbohydrate intolerance and small intestinal bacterial overgrowth (SIBO) (3). Brain Fogginess (BF) describes a constellation of symptoms comprised of mental confusion, impaired judgment, poor short-term memory, and difficulty with concentration, which is often transient and disabling. Previously, similar symptoms, along with slurred speech and gait disturbances have been described in patients with short bowel syndrome (4,5). These patients were found to have metabolic acidosis with elevated levels of D-lactic acid in the serum. The L-isomer of lactic acid is the main form of lactic acid in the human body and is produced by the enzymatic (L-lactate dehydrogenase) reduction of pyruvate. D-lactate is produced in much smaller quantities by the enzyme D-2-hydroxyl acid dehydrogenase that also metabolizes D-lactate in the human liver (4).  In a healthy gut, D-lactate levels remain low because production is limited and clearance is efficient. However, in SIBO or severe dysbiosis, there is an overgrowth of bacteria—particularly species like Lactobacillus—that ferment carbohydrates into D-lactate (2). In short bowel syndrome, if the colon is colonized by D-lactate producing bacteria, the delivery of large amounts of unabsorbed carbohydrate causes rapid fermentation, gaseous distension, and production of large amounts of d-lactic acid overwhelming hepatic clearance (6) and causing D-lactic acidosis and encephalopathy. When excess carbohydrates reach the small intestine, these bacteria rapidly convert them into D-lactate, which is then absorbed into the bloodstream. Unlike L-lactate, the human body metabolizes D-lactate more slowly, leading to accumulation. This buildup can result in D-lactic acidosis, characterized by metabolic acidosis and a range of neurological symptoms. Patients may present with confusion, brain fog, slurred speech, ataxia, or unusual behavior—often episodic and sometimes mistaken for psychiatric or neurologic disorders. Risk factors include short bowel syndrome, but it is increasingly recognized in patients with SIBO and significant gut dysbiosis, especially when high carbohydrate intake fuels bacterial fermentation. Probiotics and D-Lactic Acidosis The enzyme lactate dehydrogenase catalyzes the interconversion of pyruvate and lactate, stereospecific for the L-isomer (L-lactate), the predominant form synthesized and metabolized in humans. Although D-lactate is not a major component of normal mammalian metabolism, it can be produced in significant amounts by certain bacteria and yeast, particularly within the gastrointestinal tract. Probiotics are considered to be safe and beneficial including improvement in gut barrier function and gut transit (7). Although a meta-analysis of 57 studies indicated that probiotics are safe (8), caution against its use has been recommended in subjects who are immunosuppressed, pregnant, and with structural heart lesions, acute abdomen, neutropenia, chemotherapy and radiotherapy (8,9).  Recently, probiotic use has been implicated in the production of D-lactic acidosis, both in short bowel syndrome patients and in the first 2 weeks of life in infants who were fed probiotic-containing formula (10,11). Typically, D-lactic acidosis is caused by the fermentation of ingested carbohydrates by D-lactic producing bacteria such as lactobacillus and bifidobacterium in the bowel (4,5).  Lactobacillus species and bifidobacterium are the most common bacteria in probiotic formulations (7,12) and are felt to be useful in the treatment of irritable bowel syndrome, inflammatory bowel disease, and other intestinal problems (13). Both bacteria produce D-lactic acid. D-lactic acidosis has been described with Salmonella enteritidis and with probiotics (14). Probiotics are designed to deliver bacteria to the colon but whether this is achieved has not been reliably shown (7,12-15). In contrast, they may colonize the small bowel, especially in the presence of dysmotility or low acid conditions that favor bacterial overgrowth.  Interestingly, some Lactobacillus species such as Lactobacillus GG only produce L-lactate (14,16). Hence, both D-lactate and L-lactate should be measured when assessing this condition, and the most practical way for its diagnosis is to administer a carbohydrate meal and assess D-lactate in urine and L-lactate in blood, over the next 3 h along with breath samples for hydrogen and methane. Management focuses on reducing D-lactate production and correcting the underlying imbalance. This may include dietary carbohydrate restriction, targeted antibiotics for SIBO, probiotics in select cases, and correction of acid-base disturbances. Reference Study  Rao et al. (1) studied a cohort of patients with an intact gut who reported brain fogginess associated with unexplained abdominal bloating, pain, gas and distension, and in whom there was evidence of probiotic use, D-lactic acidosis and SIBO. They found that over 2/3rd of patients with brain fogginess exhibited D-lactic acidosis, along with significantly higher prevalence of SIBO when compared to those without brain fogginess. Symptoms improved with the use of antibiotics and stopping probiotics. Hence, they advise caution against excessive and indiscriminate use of probiotics especially without a well-defined medical indication, and particularly in patients with gastrointestinal dysmotility, and/or those using long term PPI and opioids (1). Conclusion In summary, D-lactic acidosis is a clinically important but often overlooked consequence of SIBO and gut dysbiosis.  D-lactic acidosis is a rare but clinically significant subtype of lactic acidosis, typically observed in patients with short bowel syndrome or other forms of gastrointestinal malabsorption. In these individuals, undigested glucose and starch are fermented by colonic bacteria into various organic acids, including D-lactic acid—an isomer that humans metabolize poorly. Systemic absorption of