Butyric acid – a well-known molecule revisited - PMC

Abstract

The properties of butyric acid, and the role it plays in the gastrointestinal tract, have been known for many years. However, the newest research shows that butyric acid still remains a molecule with a potential that has not as yet been fully exploited. The article provides an outline of relevant up-to-date knowledge about butyric acid, and presents the expert position on the clinical benefits of using butyric acid products in the therapy of gastrointestinal diseases.

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Keywords: butyric acid, irritable bowel syndrome, inflammatory bowel disease, constipation, diarrhea

Introduction

The properties of butyric acid, and the role it plays in the gastrointestinal tract, have been known for a long time now. However, butyric acid is still subject to intensive research which shows that it is a factor in the pathogenesis of gastrointestinal diseases, and has a range of previously unknown properties and potential therapeutic applications. Butyric acid remains a molecule with a potential that has not as yet been fully elucidated and realized.

The article provides an outline of relevant up-to-date knowledge about butyric acid, and presents the position of gastroenterology and surgery experts on the clinical benefits of using butyric acid products in the therapy of patients with gastrointestinal diseases. Since the article is a follow-up to the study published in [1], a number of issues already addressed in detail in the previous publication are left out, including the formation and roles of butyric acid in the gastrointestinal tract, problems associated with its deficiency, clinical indications and basic use recommendations.

Immunomodulatory activity of butyric acid in the gastrointestinal tract

Research conducted in recent years provides evidence for the long postulated mechanism of action of butyric acid, i.e. its effect on the gastrointestinal immune system. In studies on mice, Furusawa et al. [2] showed that the concentration of butyric acid on the colonic wall stimulates the differentiation of Treg lymphocytes, reducing the severity of inflammation induced by the transfer of TCD4+ CD45RBhi lymphocytes into Rag1&#;/&#; mice. Furthermore, in an in vitro study on undifferentiated T cells incubated with butyric acid, the authors demonstrated an increased acetylation of histone H3, which points to a possible mechanism by which butyric acid (produced by bacteria residing in the gastrointestinal tract) affects the differentiation and specialization of Treg lymphocytes. These very interesting studies have shed new light on the relationship between the host and the gut microflora, and its impact on immune homeostasis in the gut.

Gut-associated lymphoid tissue (GALT) and enterocytes (intestinal epithelial cells &#; IECs) act as the first barrier of defence against bacterial invasion through the secretion of mucins and/or defensins (antibacterial peptides) or the detection of pathogens by Toll-like receptors (TLRs). In addition, specialized IECs are capable of transporting bacterial antigens and presenting them to the immune cells in the lamina propria of the gut wall. The system becomes disturbed, for example, in the elderly, as the relationships and proportions between bacterial groups forming the microbiome are thrown off balance [3]. Similar unfavourable alterations in the microbiome composition are observed in inflammatory bowel diseases (IBD) or in irritable bowel syndrome (IBS), which is described in subsequent sections below. For many years butyric acid has been postulated to play a role of a primary messenger between commensal bacteria and the human immune system. In this understanding, the presence of butyric acid at an appropriate physiological concentration in the colonic lumen is interpreted by the body as information that the bacterial equilibrium is not disturbed, which reduces immune response and tolerance to thousands of antigens representing commensal bacteria and, hence, prevents the initiation of the inflammatory process [4].

Role of butyric acid in irritable bowel syndrome

Symptoms associated with gastrointestinal dysfunction, such as IBS, are estimated to occur in 10&#;30% of the population. The main signs of the disorder include abdominal pain, diarrhoea and altered conditions in the colon. Patients are typically advised to adopt dietary and lifestyle modifications, and are referred for psychotherapy. Pharmacological management includes antibiotics which act topically in the gastrointestinal lumen (rifaxamin) and, additionally, probiotics and in some cases antidepressants.

In one study, the microbiomes of 113 patients with IBS and 66 control subjects were analyzed. A statistically significant decrease in the amount of butyric acid-producing bacteria was found in the group of patients with IBS, particularly with IBS-D and IBS-M (p = 0.002). Also, there was a statistically significant reduction in the level of methane-producing bacteria (Methanobacteria) (p = 0.005), which increases local oxygen reservoirs and probably contributes to an increased incidence of flatulence in this patient group [5].

Considering the above, a compound which offers a high chance for success in the therapy of dysfunctional bowel disorders is sodium butyrate. In Tarnowski et al. [6] assessed the effect of sodium butyrate on selected clinical parameters in patients with irritable bowel syndrome during a 6-week follow-up. The patients were divided into two groups: control group (29 patients) receiving standard treatment with trimebutine and mebeverine (depending on the characteristics of the disease) throughout the entire follow-up period, and study group receiving sodium butyrate at 300 mg daily as an add-on to standard therapy. At baseline and 6 weeks into the study, a questionnaire was completed to assess the symptoms of the disease (on a scale from 0 to 5) and the quality of life IBS-QoL (on a scale from 0 to 100). At the time of inclusion in the study, there were no differences between the patient groups in the severity of discomfort and pain, bowel movement disorders, severity of flatulence and other gastrointestinal and IBS-associated symptoms. After 6 weeks, a statistically significant improvement was observed in the study group for the symptoms listed above. What is more, a significant improvement was achieved in the subjective assessment of the quality of life in all patients receiving sodium butyrate.

In Banasiewicz et al. [7] conducted a randomized clinical trial in a group of 66 patients with a long history of IBS diagnosed on the basis of the ROME II Diagnostic Criteria. The patients were divided into the control group (n = 32) and the study group receiving sodium butyrate (n = 34) at 300 mg/day (2 × 150 mg). The follow-up was 4, and then 12 weeks, with data collected using the Visual Analogue Scale for IBS (VAS-IBS). The following symptoms were assessed: pain in the epigastric region, incidence of flatulence, bowel movement disorders, mucus in stool and the quality of life (based on the IBS-QoL questionnaire). Four weeks after the start of the study, a significant decrease in the incidence of epigastric pain and a reduction in the severity of pain after meals were noted in the group receiving sodium butyrate. After 12 weeks, there was a statistically significant decrease in the incidence of all the symptoms studied, accompanied by an improvement in the patients&#; QoL. In subsequently published results [8], based on the closed question (yes or no) &#;Did you achieve good relief from abdominal discomfort or pain associated with IBS during the last week preceding the follow-up visit?&#;, &#;Yes&#; answers were achieved respectively in 32 and 6.25% of the patients (p < 0.01) in the study and control groups at week 4 of the study, and in 53 and 15.6% of the patients (p < 0.01), respectively, at week 12 of the study. Importantly, patients in both groups continued previously prescribed therapy (e.g. drotaverine, trimebutine) throughout the whole duration of the study, and received standard treatment for at least 3 months before the inclusion in the study. The authors concluded that butyric acid used as adjunct therapy in the treatment of IBS reduced the incidence of selected clinical symptoms, however without any effect on their severity.

Abdominal pain in patients with IBS is typically a result of disorders related to digestion and fermentation, and the build-up of gases in the gut lumen. The underlying causes of functional diseases have not been fully investigated and require further study, however existing hypotheses suggest that pain is a consequence of transmission abnormalities in the gut-brain axis. In patients with intestinal dysfunctions (IBS) sodium butyrate is one of the key factors contributing to gut homeostasis, enhancing natural processes of healing and regeneration in the intestinal epithelium. A decreased incidence of pain characteristic of IBS may be attributable to a diminished receptor sensitivity in the gut [9]. Based on an animal model butyric acid was shown to have an ability to increase the neuronal concentration in the Enteric Nervous System via phenotypic changes in the enteric neurons [10], which in turn has a favourable effect on colonic transit [11].

Another study assessed the efficacy of butyric acid in IBS. Fifty patients with IBS were divided into two subgroups &#; IBS with constipation (IBS-C) and IBS with diarrhoea (IBS-D) &#; and treated with butyric acid in the form of enteric-coated tablets at a dose of 1 g/day. The IBS form and the severity of symptoms were recorded at baseline and at the end of the study. Butyric acid treatment resulted in a reduction or normalization of symptoms in 71% of patients with IBS-D and in 16% of patients with IBS-C (p < 0.005) [12].

As of today, more than 1,000 bacteria residing in the human gastrointestinal tract have been detected. A vast majority of them belong to about a dozen genera. In adults, Firmicutes and Bacteroidetes are the most abundant phyla, and the Firmicutes to Bacteroidetes ratio appears to determine the bacterial balance in the gastrointestinal tract (in healthy adults Firmicutes is the dominant phylum, however the proportion evolves with age and changes as a result of specific pathological processes) [13]. Pozuelo et al. [5] studied the microbiome in 113 patients with IBS and 66 healthy individuals. Stool samples were collected from the study&#;s subjects twice, at a monthly interval. Bacterial diversity in patients with IBS was found to be reduced in a statistically significant manner, which resulted from a considerably lower abundance of butyrogenic bacteria (p = 0.002, q < 0.06), particularly in patients with IBS-D and mixed IBS. The findings of the study are important for considering the benefits of using probiotics in patients with IBS. The most popular probiotic products contain lactic acid bacteria. Assuming colonic colonization with these strains, an increase in local lactate production can be achieved. Tsukahara et al. identified among the commensal bacteria residing in the human gastrointestinal tract a group of Megasphaera elsdenii bacteria belonging to Firmicutes which have an ability to convert lactates into butyrate [14]. Perhaps the same mechanism is responsible for the observed efficacy of lactic acid bacteria in IBS.

Functional constipation

The composition of bacterial flora is determined by two main classes of bacteria: Firmicutes (a phylum of common Gram-positive bacteria comprising, among others, Clostridium, lactic bacteria and butyric-acid producing bacteria) and Bacteroidetes (Gram-negative rods classified as obligate anaerobes), making up 90&#;99% of the total microbiome; Firmicutes is the dominant phylum (50&#;80% of the microbiome) [15].

A study conducted in a group of 161 individuals aged 65&#;96 years showed that their stool microbiota composition (assessed by molecular biology methods), compared to that determined in nine young volunteers (28&#;46 years old), shifted significantly toward Bacteroidetes [16].

Basic research in an animal model demonstrated that butyric acid increased the effectiveness of peristalsis by improving colonic smooth muscle contractility and regulating neurotransmission, particularly in cases of impaired peristalsis accompanying functional constipation in the elderly [17].

A double-blind, randomized, placebo-controlled study conducted in a group of 11 healthy volunteers involved self-administration of enemas by the study&#;s subjects according to the following regimen: enema with 100 mmol/l of butyric acid in week 1; 50 mmol/l of butyric acid in week 2; and placebo (saline solution) in week 3 of the study. At the start and end of each test period, a rectal barostat measurement was performed to determine the severity of pain, discomfort, and the urge to pass gas or stool. Butyric acid administered at 50 mmol/l resulted in a decrease in pain score by 23.9%, at 100 mmol/l &#; by 42.1%; and a decrease in discomfort score by 44.2% and 69.0%, respectively, at a pressure of 4 mm Hg. The authors concluded that rectal administration of butyric acid led to a dose-dependent decrease in visceral sensitivity which plays a key role in disorders of intestinal motility (including functional constipation), abdominal pain or discomfort [18].

A beneficial effect of butyric acid as one constituent of a multifaceted mechanism modulating gastrointestinal function has also been stressed in patients with stoma and coexisting constipation. Butyric acid supplementation combined with the use of probiotics should be adopted as one of the basic therapeutic strategies in this patient group, preceding treatment with laxatives [19].

Sodium butyrate has also been introduced into the algorithm of dietary treatment in patients with stoma [20].

Diarrhoea

Sodium butyrate may also prevent diarrhoea through an increased passive absorption of water in the colon and its effects on the gut microflora [21].

Butyrate is easy to administer and counteracts acute dehydration; it may be used in long-term treatment and prevention of traveller&#;s diarrhoea affecting individuals moving from countries with higher hygienic standards to destinations with a lower hygienic status. Even though antibacterial substances bring rapid and tangible therapeutic benefits in the treatment of traveller&#;s diarrhoea, there is no possibility to prevent the illness. In addition to standard recommendations such as additional caution about hygiene and food, travellers are advised to eat warm foods, drink bottled water, and eat only fruit and vegetables with intact skin. Pharmacological recommendations include rifaxamin, fluoroquinolone and Lactobacillus bacteria. Krokowicz et al. [22] made an attempt to demonstrate the preventive activity of a mixture of organic acids in a lipid matrix (250 mg of sodium butyrate; 100 mg of fumaric acid; 60 mg of citric acid; 50 mg of sorbic acid; 40 mg of malic acid) in traveller&#;s diarrhoea. A total of 42 patients completed the study, including 20 in the placebo group and 22 individuals taking the acid mixture 3 days before the journey. The incidence of traveller&#;s diarrhoea was 4.5% in the treatment group, and 40% in the placebo group. In addition, a statistically significant improvement was noted in the study group in terms of reduction in the number of bowel movements a day and relief of gastric symptoms (abdominal pain, nausea). Similar beneficial effects are observed after using a mixture of sodium butyrate and silicon dioxide (A300) [23].

Persistent and difficult-to-treat diarrhoea is one of the more common side effects of chemo- and radiotherapy in cancer treatment [24]. Karakulska-Prystupiuk [25] described the case of a patient with diarrhoea which developed during the period of myelosuppression in chemotherapy administered for anaplastic lymphoma. The differential diagnosis included recurrence of the primary disease and gastrointestinal tract infection. Subsequent microbiological tests excluded bacterial and fungal diarrhoea, and cytomegalovirus infection. Diarrhoea caused a considerable weight loss: 12 kg over 2 months. Dietary supplementation with butyric acid at 300 mg daily was initiated. After just several days the patient reported a substantial relief of symptoms and elimination of diarrhoea. In addition, the patient reported an elevated appetite and an increased frequency of meals. During successive follow-up examinations the patient was found to gradually return to his normal body weight.

Non-specific inflammatory bowel diseases

Butyric acid shows a protective effect in inflammatory response secondary to inflammatory bowel diseases. Recent research indicates that chronic stimulation by interferon γ (IFN-γ) plays an important role in the formation of inflammation-associated colon cancer, and the development of colitis ulcerosa is linked to the gene encoding IFN-γ. An in vitro study conducted on human intestinal epithelial cells sampled from the colon of patients with colitis ulcerosa showed an increased infiltration with unspecified T cells in the mechanism of activation of the signal transducer and activator of transcription 1 (STAT1). Butyric acid was also demonstrated to effectively inhibit STAT1 activation by reducing IFN-γ production, which results in the apoptosis of T cells of unspecified type and the suppression of the inflammation [26].

Molecular biological methods offer a possibility to gradually identify the relationship between the microbiome, diet, immune response and, consequently, the development of inflammatory bowel diseases. Experience shows that bowel inflammation may be induced by fat-rich diet. In one study, the composition of the microbiota in intestinal biopsies and stool samples was assessed using gene sequencing methods in a group of 231 subjects. One of the findings was a decrease in the amount of Anaerostipes bacteria belonging to Furmicutes in IBD patients who are active smokers or have a history of smoking. Similarly to Megasphaera elsdenii discussed above, Anaerostipes are bacteria responsible for the conversion of lactate to butyrate. In addition, the study revealed that patients with IBD had a reduced amount of Roseburia and Phascolarctobacterium bacteria which produce butyric and propionic acids in the colon [27]. The described ability of some bacteria to convert lactates to butyric acid may also be effectively induced by the commercially available mixture of eight lactic acid-producing probiotic bacteria &#; VSL#3 (Lactobacillus plantarum, Lactobacillus delbrueckii subsp. Bulgaricus, Lactobacillus paracasei, Lactobacillus acidophilus, Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis and Streptococcus salivarius). Studies in humans who used VSL#3 orally showed the preparation to reduce the clinical symptoms and severity of the inflammatory process in patients with pouchitis (after pancolectomy due to colitis ulcerosa) [28], and mild and moderate colitis ulcerosa [29].

A beneficial effect of sodium butyrate in post-proctocolectomy patients has also been demonstrated in research undertaken by the authors of the present publication. In a group of patients with pouchitis, sodium butyrate was found to be a beneficial element of combined therapy, accelerating the remission of symptoms &#; primarily diarrhoea and pain. However, the main effect linked to sodium butyrate was a reduction in the incidence and severity of inflammation in patients taking microencapsulated sodium butyrate at 2 × 200 mg [30].

A high concentration of IgA-coated bacteria plays a role in inducing inflammatory bowel diseases, mainly Crohn&#;s disease. A group of researchers [31] assessed the effect of sodium butyrate on the composition of the microbiota in IBD-prone IL-10&#;/&#; mice. At 8 weeks old, the mice were divided into three groups (four pergroup): normal (C57BL/6 &#; negative control), IL-10&#;/&#; (positive control) and IL-10&#;/&#; treated with sodium butyrate administered in drinking water (study group). The severity of colitis symptoms, and the concentrations of proinflammatory cytokines and short-chain fatty acids were assessed in the proximal section of the colon, whereas the percentage of IgA-coated bacteria and the microbiota composition in stool samples were evaluated by 16S ribosomal RNA analysis 4 weeks after the initiation of treatment. The study found that sodium butyrate reduced the histologically observed severity of colitis and decreased the level of tumor necrosis factor α (TNF-α) and IL-6 in IL-10&#;/&#; mice treated with sodium butyrate compared with the positive control. At the level of microbiota composition, a reduction in IgA-coated and Bacteroidetes bacteria, and an increase in the group of Firmicutes, were noted in IL-10&#;/&#; mice treated with sodium butyrate. The authors concluded that sodium butyrate lowered the risk of colitis, possibly by modifying the composition of the microbiota, i.e. enriching its biodiversity and reducing the amount of colitogenic IgA-coated bacteria.

Effect in cancer prevention and treatment

A study by Zhang et al. [32] analyzing human colorectal cancer cell lines (HCT-116 and HT-29) treated with sodium butyrate at concentrations ranging from 0.5&#;5 mM found that sodium butyrate inhibited the growth of the studied cancer cells, stimulated autophagy and induced apoptotic cell death, thus revealing a new possible mechanism underlying the anticancer activity of butyric acid.

Mouse studies revealed a 75% reduction in the risk of colon cancer in animals fed fibre-rich diets in a mechanism with butyric acid-producing colonic bacteria acting as intermediaries &#; compared to bacteria-free mice. It is concluded that the presence of bacteria producing butyric acid is a prerequisite for a fibre-rich diet to exert its beneficial effect which has been extensively described in the literature [33].

Another interesting role of sodium butyrate was described by Bueno-Carrazco et al. [34]. The authors found that oral administration of sodium butyrate supports the anti-cancer efficacy of photodynamic therapy in astrocytoma cells, most likely in a mechanism based on the modulation of gene expression and differentiation of cancer cells.

The synergistic cytotoxic effect on cancer cells was also demonstrated in a study conducted by Encarnacao et al. [35]. The authors showed that butyric acid increased the sensitivity of resistant cancer cells to irinotecan, a second-line drug used in the treatment of colon cancer. The finding may put a new perspective on the application of irinotecan which is regarded by clinicians who balance benefit against risk in the choice of therapy as a drug associated with uncertainty and interindividual variability of response. In vitro observations of colon cancer cell lines conducted over a period of up to 96 h showed a significant inhibition of cancer cell proliferation in the group where the cells were simultaneously exposed to irinotecan and butyric acid, compared to the group where only irinotecan was used.

The same group of researchers performed an in vitro assessment of the effect of butyric acid on the uptake of the 18F-labelled glucose analogue (18F-FDG) and the increase in glycolysis in a colon cancer cell line [35, 36]. The results show that the addition of butyric acid reduces the uptake of 18F-FDG and may affect the Warburg effect which is correlated with tumour aggressiveness. The greatest differences were observed at the lowest labelled glucose concentrations which, in turn, most accurately reflects the clinical situation. Furthermore, the results of the study suggest that butyric acid may play a role in cancer cells at an advanced stage of development.

Other applications of butyric acid

In a randomized prospective clinical trial patients with clinically diagnosed diverticulosis (n = 73) were assigned to the control and study groups. The study group received sodium butyrate at 300 mg/day (2 × 150 mg) with a follow-up examination after 12 months. The study was completed by 30 patients receiving sodium butyrate and 22 control group patients receiving placebo. Patients in the study group declared a decrease in the frequency of clinical symptoms of diverticulosis and a significant reduction in the sensation of abdominal discomfort and pain compared to the placebo group [37].

Sodium butyrate in the form of enemas (combined in a mixture with A-300 silicon dioxide) may be a successful method of therapeutic management in patients with radiation proctitis. Sodium butyrate was shown to have an ability to reduce inflammation, as confirmed by clinical and endoscopic assessment. A key aspect related to sodium butyrate which appears to be of great relevance for this challenging and treatment-resistant form of proctitis is a multifaceted mechanism of action of butyrate which prevents inflammation, stimulates proliferation and normalizes the profile of secreted mucus [38].

Conclusions

The body of knowledge about the roles and importance of butyric acid has been expanding steadily, and the mechanisms by which butyric acid affects the relationship between the microbiome and the host are becoming increasingly elucidated. It is currently believed that the clinical aspects of using butyric acid described above arise from the effect of the compound on the local immune system, the mechanisms regulating the gut peristalsis, the severity of inflammatory processes and the regulatory mechanisms of the gut-brain axis [39]. The complex mechanism of action of butyric acid seems to play a vital role in maintaining symbiosis and homeostasis in the human body.

The scope of the present article is limited to oral butyric acid preparations used at doses which provide no possibility for significant quantities of butyric acid to pass into the systemic circulation. Consequently, it excludes studies focused on the role of butyric acid in reducing peripheral insulin resistance in diabetes mellitus type 2 [40] or preventing body weight gain [41], which represent important future challenges for pharmaceutical companies. The coming years are bound to bring new discoveries and fascinating reports on other areas of activity of butyric acid, and therefore new therapeutic opportunities associated with its use.

Conflict of interest

The authors declare no conflict of interest.

Used in food, cosmetics and even agriculture. Butyric acid is not only versatile, but also has a range of health benefits.

Also known as butanoic acid, it is a fascinating ingredient that can be just as versatile in your body. It is believed to counteract inflammation or regulate insulin metabolism, for example. What's more, your body produces it on its own, helped by probiotic bacteria.

From this article you will learn:

• What is butyric acid and how it differs from sodium butyrate.
• How it works.
• How butyric acid works and how it is synthesised in the body.
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• What ailments can butyric acid help with.
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• How to ensure the right concentration of butyric acid in the body.
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• Whether butyric acid can cause harm.
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See also:

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What is butyric acid?

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Butyric acid, also known as butanoic acid, is a short chain fatty acid ( short chain fatty acids - SCFA) that plays a key role in gut health. It is produced by the bacteria that live in your digestive system.

Wondering how it works? When you eat fibre that is indigestible to your body, it passes into the large intestine. There, probiotic bacteria residing in the colon convert this fibre into butyric acid. This is a perfect example of symbiosis, where both parties benefit - the bacteria have nourishment and you get an essential substance for your health .

Butyric acid is extremely important for your gut. It acts as a kind of fuel for the epithelial cells lining the colon, helping them to maintain a healthy intestinal barrier. This is important because this barrier prevents harmful substances from entering your body .

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As early as the s, studies were conducted that conclusively established butyric acid as a major source of energy for colonocytes, offering hope for its use in the prevention and treatment of gastrointestinal diseases.

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Katarzyna Grajpermagister of pharmacy

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What's more, butyric acid has anti-inflammatory properties, which may help to relieve inflammation in the gut. Some studies also suggest that it may help regulate blood sugar levels and improve metabolism. However, these are preliminary and inconclusive conclusions, so should be approached with caution .

So it is worth paying attention to your diet and making sure you are providing your body with enough fibre. By doing so, the probiotic bacteria will be able to produce butyric acid, which will contribute to your gut health.

Butyric acid versus sodium butyrate

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Sodium butyrate is the sodium salt of butyric acid, or a derivative of it. The molecules of butyric acid and butyrate are chemically different . However, the properties of the two substances are so similar that their names are often used interchangeably.

In practice, the sodium atom in butyrate makes this butyric acid derivative more stable. It is for this reason that you will most often encounter sodium butyrate in dietary supplements.

Sodium butyrate is the most common name.

Best for digestion

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• Sodium butyrate content per daily serving: mg
• Form: capsules
• Package: 60 capsules
• Serving size: 3 capsules per day
• Sufficient for: 30 days

See priceProduct description

Premium Sodium Butyrate is a natural support for your digestive system. With a high dose of butyric acid (940 mg), it supports the regeneration of the intestinal mucosa, improving gut health and function, and aids in the absorption of nutrients. By taking care of your intestines, you're taking care of the health of your entire body.

Studies involving people suffering from irritable bowel syndrome confirm that sodium butyrate is ideal for supporting issues related to bacterial flora imbalances (for example, after antibiotic therapy), constipation and diarrhea, inflammation of the intestinal mucosa, or a diet low in fiber.

Premium Sodium Butyrate capsules are made using the innovative DRcaps® technology. This guarantees that the active ingredients in the product are protected from the destructive effects of stomach acids and digestive enzymes. As a result, we can be sure that the beneficial ingredients are released in the small intestine and are fully absorbed by our body.

Premium Sodium Butyrate from Natu Care is 100% tested, and its composition contains only the highest quality raw materials.

Pros and cons

Pros:

• Supports digestive system function
• Helpful for various gastrointestinal conditions, including IBS
• High dose of butyric acid in each capsule
• Eco-friendly, clean, and tested composition
• Free from added sugar, gluten, GMOs, and lactose
• Innovative capsule technology - DRcaps

Cons:

• None

Additional Information

Take 3 capsules daily at any time of the day, preferably with a meal. Swallow the capsules whole with water.
Premium Sodium Butyrate is intended for adults.
The product should be used under medical supervision.

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I've been using the product for 2 weeks. My stomach feels lighter, and my digestion has improved. I recommend it.

Properties of butyric acid

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Butyric acid is a key ingredient for the proper functioning of the epithelial cells of the colon, called colonocytes. It provides up to 70% of the energy these cells need to function . 

This, however, is not the only function that butyric acid has in our bodies. It is currently the subject of scientific research to understand its potential effects on the immune system and its ability to reduce inflammation. In addition, its properties affecting insulin regulation are also being studied.

Although the exact mechanism of action of butyric acid at the biochemical level is not yet fully understood, there is some evidence to suggest that it may affect various aspects of bodily function. This may include :

• impact on the immune response, 
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• cell differentiation,
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• natural process of elimination of defective and damaged cells,
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Butyric acid may also help to strengthen the protective barrier in the intestines by participating in the production of the mucus that lining them .

Applications of butyric acid

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Are you interested in learning more about butyric acid benefits? Contact us today to secure an expert consultation!

Butyric acid is a well-known ally in the fight against various digestive problems. First and foremost, this metabolite plays a key role in protecting and regenerating the end sections of the digestive system .

It is also an effective solution if you are struggling with problems such as bloating or constipation. Butyric acid aids intestinal peristalsis, which in practice means that it facilitates the bowel movement process. 

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The usefulness of butyric acid in infectious diarrhoea has also been clinically confirmed. This is related, among other things, to the mechanism of regulation of water and electrolyte absorption in the cell membrane of colonocytes.

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Katarzyna Grajpermagister of pharmacy

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What's more, butyric acid helps to control gas accumulation in the intestines. As a result, you are able to reduce the unpleasant bloating that can cause discomfort .

It is also worth adding that some studies suggest additional benefits for your body. Some scientific work has shown that butyric acid may contribute to maintaining a healthy body weight, by regulating metabolic processes related to insulin and lipid production . 

Do not, however, consider butyric acid (or its derivative, sodium butyrate) as a weight-loss agent. There is still a dispute among scientists about how butyric acid affects our metabolism. 

Most studies are in vitro experiments or those involving animals. There are also researchers who point in their work to links between high concentrations of butyrate or butyric acid and metabolic disorders and cardiovascular disease - as you can see, in this case, what's too much is unhealthy .

Butyric acid for the gut

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Butyric acid has many important functions in your intestines. Not only is it a source of energy for the cells of the colon, but it also supports their regeneration. In addition, it supports the production of mucus, which is an important part of the protective intestinal barrier .

Thanks to this, butyric acid helps to protect your body from harmful substances and pathogens that could enter the bloodstream through this route.

Animal studies suggest that butyric acid may provide relief from irritable bowel syndrome (IBS) symptoms, such as abdominal pain or irregular bowel movements . 

A study review indicates that butyric acid derivatives may be helpful in the treatment of colorectal cancer. The results suggest that the ingredient may induce cancer cell death, improve the efficacy of radiotherapy and protect mucosa from degradation that can occur during chemotherapy .

Butyric acid provides energy to healthy cells and at the same time may inhibit the growth of cancerous ones, a phenomenon known as the Warburg effect. Therefore, there is a hypothesis that certain strains probiotics may exhibit anti-cancer effects .

Butyric acid is also used by intestinal cells to produce energy, which increases oxygen consumption by the epithelium. As a result, the presence of butyric acid-producing bacteria helps to maintain an anaerobic environment in the intestines, which further protects against the colonisation of aerobic pathogens such as Salmonella or bacteria E. coli.

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What is butyric acid found in?

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Butyric acid is not only found in your intestines. Some foods - especially milk and milk products (dairy products), for example butter, cream, yoghurt or hard yellow cheeses - also contain small amounts of it. Support for butyric acid synthesis can also be provided by products rich in probiotics and prebiotics.

By increasing the amount of probiotics in your gut, you increase the amount producers of butyric acid. And by eating prebiotic foods, you provide them with the necessary materials for this production.

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Products rich in probiotics

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Products rich in prebiotics (GOS and FOS fibre)*

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• yoghurt,
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• kefir,
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• buttermilk,
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• sugared milk,
• sugared milk,
• flax,
• flax,
• buttermilk,
• sugared milk,
• flax.
• miso,
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• tempeh,
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• sauerkraut,
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• pickled cucumbers,
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• cold boiled potatoes,
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• artichokes,
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• asparagus,
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• broccoli,
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• carrots,
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• garlic,
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• soy,
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• legumes,
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• peas,
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• apple,
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• currants,
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• morels,
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• bananas,
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• kiwi,
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• raspberries,
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• oranges,
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* GOS and FOS fibre are oligosaccharides, or complex carbohydrates (fructooligosaccharides and galactooligosaccharides), which do not digest in the stomach but are only fermented in the large intestine - providing food for probiotic bacteria and contributing to butyric acid production.

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Best results will be achieved by using different fibre fractions from three different groups including cereals, vegetables and fruit. Also ensure adequate hydration.

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Katarzyna Grajpermagister of pharmacy

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Butyric acid sweetness

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Butyric acid is considered safe, but there are situations in which its use must be abandoned.

Do not take butyric acid or its derivatives (butyrate) if :

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• you are allergic to butyric acid or any other ingredient in the supplement,
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• you have kidney problems, as butyric acid is removed from the body specifically by the kidneys,
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• you suffer from heart disease, as butyric acid can affect sodium levels in the body, which can be dangerous,
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• you should limit fibre in your diet because of certain digestive ailments,
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• you are pregnant or breastfeeding - the safety of using butyric acid during these periods is not well studied,
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• you are taking any medication - in which case consult your doctor before starting supplementation, as butyric acid may interact with some substances.

Despite its benefits, butyric acid can cause some side effects, although this is rather rare. The most common are gastrointestinal problems such as increased bowel function, nausea, abdominal pain and diarrhoea, and changes in appetite . 

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Often these symptoms disappear after a few days, but if they are bothersome or worsen, you should stop supplementation and consult your doctor.

The effects of allergic reactions are a different matter. Their symptoms are :

• rash, 
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• catarrh, 
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• swelling,
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• difficulty breathing, 
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If this occurs, discontinue use of the butyric acid preparation immediately and contact your doctor.

See also:

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Summary

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• Butyric acid is a metabolite of the fermentation of fibre by probiotic bacteria that inhabit the large intestine.
• Butyric acid is the main source of energy for colon epithelial cells. It also has protective and regenerative functions.
• Butyric acid can promote intestinal peristalsis and support the production of mucus, which is part of the natural intestinal barrier.
• The effects of butyric acid and its derivative, butyrate, in the context of influencing insulin and lipid metabolism and combating inflammation in the body are currently being investigated.
• Butyrate is an important component of the intestinal barrier.
• The appropriate concentration of butyric acid in the body is best ensured by consuming foods rich in GOS and FOS fibre, as well as probiotics.
• Butyric acid can also be taken in dietary supplements. It is most commonly found in these in the form of sodium butyrate.
• Butyrate supplements are also a good way to take it.
• Supplements with butyrate or butyric acid should be avoided by people with heart disease and ailments that require restricted fibre intake.

FAQ

.. How to make butyric acid at home .

Note: butyric acid is a really smelly thing. Think twice about whether you want to make it at home (if you live in a block of flats, think about your neighbours too). Another important thing: Do not eat butyric acid obtained this way! 

To make butyric acid, all you need to do is leave the butter out of the fridge - until it goes rancid. But to be able to isolate it, you can use this recipe:

1. Melt 500ml of butter in a pot over a low heat; 
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2. Add 500 ml distilled water, stir to combine. 
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3. Pour the mixture into a jar and add 2 tablespoons of natural yogurt as a starter. 
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4. Cover the jar and keep in a warm place for 2-3 days. 
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5. After this time, strain the liquid through a thick sieve, separating the solids. 
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6. Heat the remaining liquid to 100°C until the water evaporates. 
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7. The residue that remains is butyric acid.
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. Where does butyric acid occur? .

Butyric acid occurs naturally in many products, especially butter. You will also find it in other dairy products such as cheese, cream and yoghurt. Furthermore, it is also contained in ghee, a type of clarified butter. 

Butyric acid is also produced in the human body - in the gut, as a result of the fermentation of fibre by bacteria. For this reason, eat fibre-rich foods such as fruit, vegetables, nuts, seeds and whole-grain cereal products. This is important because butyric acid has many health benefits. It has anti-inflammatory effects and supports gut health.

. What are the side effects of taking butyric acid? .

Taking butyric acid can lead to several side effects. The most common are abdominal pain, bloating, diarrhoea and nausea. For these symptoms, reduce the dose of butyric acid or divide it into several smaller portions throughout the day. This may help to minimise discomfort. Sometimes an allergic reaction may also occur.

. What is the smell of butyric acid? .

Butyric acid has an intense, unpleasant odour that is often compared to the smell of... vomit. This is due to the specific chemical structure of this acid, which contains four carbon atoms in its chain. However, in small quantities, it can contribute to the characteristic taste of some foods (especially cheese).

. What is the formula of butyric acid? .

The chemical formula of butyric acid is C4H8O2. It is a carboxylic acid that consists of four carbon atoms (C), eight hydrogen atoms (H) and two oxygen atoms (O). Carbon (C) comes first, followed by hydrogen (H) and finally oxygen (O). 

This order is important because it indicates the structure of the molecule. Other chemical formulas of butyric acid that you may encounter are C3H7COOH and CH3(CH2)2COOH.

. How much does butyric acid cost? .

Dietary supplements containing butyric acid, or more commonly its derivative - sodium butyrate - cost from around £30 to £150. Differences in price may be due to the quality of the raw material itself, the size of the packaging and the additional active ingredients used in the formulation.

. Is butyric acid in medicinal form? .

Butyric acid (also in the form of sodium butyrate) is only available in Poland as a dietary supplement. You can find it in health food shops or pharmacies. Only buy products from trusted manufacturers to ensure the best quality and safety. 

Butyric acid is important for intestinal health, as it is the main source of energy for intestinal epithelial cells. An example of a product containing butyric acid in the form of sodium butyrate is Panaseus Formula for the Gut.

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Resources

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Amiri, P., Hosseini, S. A., Roshanravan, N., Saghafi-Asl, M., & Tootoonchian, M. (). The effects of sodium butyrate supplementation on the expression levels of PGC-1α, PPARα, and UCP-1 genes, serum level of GLP-1, metabolic parameters, and anthropometric indices in obese individuals on weight loss diets: A study protocol for a triple-blind, randomized, placebo-controlled clinical trial. Trials, 24(1), 489. https://doi.org/10./s-022--9

Banasiewicz, T., Domagalska, D., Borycka-Kiciak, K., & Rydzewska, G. (). Determination of butyric acid dosage based on clinical and experimental studies - a literature review. Gastroenterology Review/Review of Gastroenterology, 15(2), 119-125. https://doi.org/10./pg..

Birt, D. F., Boylston, T., Hendrich, S., Jane, J.-L., Hollis, J., Li, L., McClelland, J., Moore, S., Phillips, G. J., Rowling, M., Schalinske, K., Scott, M. P., & Whitley, E. M. (). Resistant Starch: Promise for Improving Human Health. Advances in Nutrition, 4(6), 587-601. https://doi.org/10./an.113.

Borycka-Kiciak, K., Banasiewicz, T., & Rydzewska, G. (). Butyric acid - a well-known molecule revisited. Gastroenterology Review/Review of Gastroenterology, 12(2), 83-89. https://doi.org/10./pg..

Butyric Acid-An overview | ScienceDirect Topics. (n.d.). Retrieved November 10, , from https://www.sciencedirect.com/topics/medicine-and-dentistry/butyric-acid

Candido, E. P. M., Reeves, R., & Davie, J. R. (). Sodium butyrate inhibits histone deacetylation in cultured cells. Cell, 14(1), 105-113. https://doi.org/10./-(78)-7

De la Cuesta-Zuluaga, J., Mueller, N. T., Álvarez-Quintero, R., Velásquez-Mejía, E. P., Sierra, J. A., Corrales-Agudelo, V., Carmona, J. A., Abad, J. M., & Escobar, J. S. (). Higher Fecal Short-Chain Fatty Acid Levels Are Associated with Gut Microbiome Dysbiosis, Obesity, Hypertension and Cardiometabolic Disease Risk Factors. Nutrients, 11(1), Article 1. https://doi.org/10./nu

Effects of oral butyrate supplementation on inflammatory potential of circulating peripheral blood mononuclear cells in healthy and obese males | Scientific Reports. (n.d.). Retrieved November 3, , from https://www.nature.com/articles/s-018--7

Frontiers | Protective role of butyrate in obesity and diabetes: New insights. (n.d.). Retrieved November 5, , from https://www.frontiersin.org/articles/10./fnut../full

Kaźmierczak-Siedlecka, K., Marano, L., Merola, E., Roviello, F., & Połom, K. (). Sodium butyrate in both prevention and supportive treatment of colorectal cancer. Frontiers in Cellular and Infection Microbiology, 12. https://www.frontiersin.org/articles/10./fcimb..

Lewandowski, K., Kaniewska, M., Karlowicz, K., Rosolowski, M., & Rydzewska, G. (). The effectiveness of microencapsulated sodium butyrate at reducing symptoms in patients with irritable bowel syndrome. Gastroenterology Review/Review of Gastroenterology, 17(1), 28-34. https://doi.org/10./pg..

Liu, H., Wang, J., He, T., Becker, S., Zhang, G., Li, D., & Ma, X. (). Butyrate: A Double-Edged Sword for Health? Advances in Nutrition, 9(1), 21-29. https://doi.org/10./advances/nmx009

Sodium butyrate in the treatment of functional and inflammatory bowel disease | Practical Gastroenterology-Practitioner's Journal. (n.d.). Retrieved November 3, , from https://gastroenterologia-praktyczna.pl/a/Maslan-sodu-w-leczeniu-chorob-czynnosciowych-i-zapalnych-jelit.html/

Miller, A. A., Kurschel, E., Osieka, R., & Schmidt, C. G. (). Clinical pharmacology of sodium butyrate in patients with acute leukemia. European Journal of Cancer and Clinical Oncology, 23(9), -. https://doi.org/10./-(87)-X

Pietrzak, A., Banasiuk, M., Szczepanik, M., Borys-Iwanicka, A., Pytrus, T., Walkowiak, J., & Banaszkiewicz, A. (). Sodium Butyrate Effectiveness in Children and Adolescents with Newly Diagnosed Inflammatory Bowel Diseases-Randomized Placebo-Controlled Multicenter Trial. Nutrients, 14(16), Article 16. https://doi.org/10./nu

Säemann, M. D., Böhmig, G. A., Österreicher, C. H., Burtscher, H., Parolini, O., Diakos, C., Stöckl, J., Hörl, W. H., & Zlabinger, G. J. (). Anti-inflammatory effects of sodium butyrate on human monocytes: Potent inhibition of IL-12 and up-regulation of IL-10 production. The FASEB Journal, 14(15), -. https://doi.org/10./fj.00-fje

Segain, J.-P., Blétière, D. R. de la, Bourreille, A., Leray, V., Gervois, N., Rosales, C., Ferrier, L., Bonnet, C., Blottière, H. M., & Galmiche, J.-P. (). Butyrate inhibits inflammatory responses through NFκB inhibition: Implications for Crohn's disease. Gut, 47(3), 397-403. https://doi.org/10./gut.47.3.397

Sodium butyrate. (n.d.). American Chemical Society. Retrieved November 3, , from https://www.acs.org/molecule-of-the-week/archive/s/sodium-butyrate.html

Spina, L., Cavallaro, F., Fardowza, N. I., Lagoussis, P., Bona, D., Ciscato, C., Rigante, A., & Vecchi, M. (). Butyric acid: Pharmacological aspects and routes of administration. Digestive and Liver Disease Supplements, 1(1), 7-11. https://doi.org/10./S-(08)-2

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Summer, A., Formaggioni, P., Franceschi, P., Di Frangia, F., Righi, F., & Malacarne, M. (). Cheese as Functional Food: The Example of Parmigiano Reggiano and Grana Padano. Food Technology and Biotechnology, 55(3), 277-289. https://doi.org/10./ftb.55.03.17.

Xu, Y.-H., Gao, C.-L., Guo, H.-L., Zhang, W.-Q., Huang, W., Tang, S.-S., Gan, W.-J., Xu, Y., Zhou, H., & Zhu, Q. (). Sodium butyrate supplementation ameliorates diabetic inflammation in db/db mice. Journal of Endocrinology, 238(3), 231-244. https://doi.org/10./JOE-18-

Zou, X., Ji, J., Qu, H., Wang, J., Shu, D. M., Wang, Y., Liu, T. F., Li, Y., & Luo, C. L. (). Effects of sodium butyrate on intestinal health and gut microbiota composition during intestinal inflammation progression in broilers. Poultry Science, 98(10), -. https://doi.org/10./ps/pez279

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