Probiotics, Nutrition, and the Small Intestine

  • Taylor C. Judkins
  • Douglas L. Archer
  • Dean C. Kramer
  • Rebecca J. SolchEmail author
Open Access
Small Intestine (D Sachar and AC Stein, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Small Intestine


Purpose of Review

Probiotics are promising remedial treatments for symptoms of small intestine (SI) diseases and promoters of overall good health. Probiotics play an important role in supporting a healthy SI microbiome (eubiosis), and in preventing establishment of unhealthy microbiota. SI eubiosis promotes optimal nutrient uptake, and optimal nutritional status maintains a healthy SI, reducing the likelihood of SI diseases. It is important to understand the advantages and limitations of probiotic therapies.

Recent Findings

Microbial dysbiosis decreases the capacity of the small bowel to utilize and absorb dietary compounds. In some studies, probiotic supplements containing lactic acid bacteria and Bifidobacterium have been demonstrated effective in supporting beneficial microbes in the SI while improving barrier integrity and reducing nutrient malabsorption and SI disease-related pathology.


Strain-specific probiotic therapy may be a natural and effective approach to restoring SI barrier integrity and eubiosis, resulting in improved nutrient absorption and better health, including reducing the incidence of and severity of SI diseases.


Small intestine Probiotics Nutrition Microbiota Dysbiosis, intestinal permeability 


The preponderance of nutrient absorption occurs in the small intestine (SI), and diseases affecting the SI may therefore disrupt nutrient absorption. Malnutrition occurs when adequate amounts of single or multiple nutrients cannot gain entry to the body compartment or gain entry in excessive or unbalanced amounts. This can be the result of SI disease pathology, or dysbiosis of the normal SI microbial flora, either of which may alter the structure and permeability of the SI epithelial barrier. Probiotics are live microorganisms that, when ingested in adequate amounts, confer a health benefit to the host [1]. Probiotics are generally regulated as either dietary supplements or medical foods (e.g., Visbiome®, a multi-strain probiotic formerly called VSL#3) in the USA. Most probiotics currently available are lactic acid bacteria (LAB), and Bifidobacterium spp., and certain yeasts such as Saccharomyces boulardii [2], which have a long history of safe use and are legally “generally recognized as safe” (GRAS). The effects of probiotics, and moreover studies on the microbial composition of the SI flora, have been hampered by limitations on access, as SI epithelial biopsies or aspirates via naso-ileal catheters are invasive procedures. Therefore, most microbiome analyses are conducted on stool which is influenced heavily by colonic microbiota. Nonetheless, recent animal studies and human clinical trials suggest that probiotics can have a restorative effect on gut integrity and nutrient uptake via promoting eubiosis in the SI.

Small Intestine


The SI, comprised of the duodenum, jejunum, and ileum, is the major site of macro- and micronutrient digestion and absorption. Digestion is accomplished through a mixture of digestive enzymes (pancreatic lipases, SI brush-border disaccharidases, etc.) as well as other secretions (i.e., bile salts and bicarbonate) active in digestive processes. Plicae circularis, transverse folds of submucosa covered by mucosa predominantly in the duodenum and proximal jejunum, are covered by villi and microvilli to increase the surface area of the SI and optimize nutrient absorption.

The gastrointestinal (GI) tract is lined with the mucosal epithelium to act as a direct barrier between the environment and host. This intestinal barrier contains various components, such as commensal gut microbiota, mucus layer, antimicrobial peptides (AMPs), and junctional complexes (i.e., tight junctions (TJs), adherens junctions, and desmosomes). These dynamic components work together to maintain normal barrier integrity [3]. Permeability of the barrier can be increased through direct damage to the epithelial mucosa or changes to other components via dysbiosis, diet, or inflammation [4].

The duodenum, jejunum, and ileum experience unique luminal environmental factors that can change each section’s microbial abundance. On average, the duodenum and jejunum contain up to 103–104 bacteria/mL followed by an increase to 108 bacteria/mL in the ileum. While the concentration of bacteria increases along the GI tract, in comparison, it is much lower than the typical concentration of the colon (1011 bacteria/mL) [5].

Modulators of SI Microbiota

SI microbiota abundance and composition can be modulated by oxygen availability, pH, transit time, AMPs, and intake of probiotics. Oxygen availability, on average, decreases from proximal to distal SI and microniches in the lumen create environments for aerobes and strict anaerobes alike to survive and metabolize.

The pH of SI regions and transit time of food content contribute to the changes in microbial density. The median pH of the proximal intestine is 6.7 with an increase to 7.5 in the terminal ileum [6]. Acidic chyme passes from the stomach into the duodenum and stimulates the hormone secretin, which in turn stimulates the liver and pancreas to release bicarbonate into the duodenum, thus increasing pH and allowing for optimal function of digestive enzymes. The basic pH within the terminal ileum may create a more favorable environment for SI microbiota to begin degradation of complex carbohydrates, ferment simple carbohydrates, and utilize energy. These processes are time-limited as food content is only in the SI for 2–5 h [7]. Unabsorbed nutrients and fiber enter the colon where they reside for 12–24 h [7], allowing for fermentation of complex carbohydrates and production of short chain fatty acids (SCFAs).

The microbial environment of the SI can also be shaped by AMPs that function as a part of the innate immune system and thus appear in greater amounts during inflammatory events triggered by dysbiosis or disease. In mice, reduced concentrations of cathelicidin-related AMP resulted in increased duodenal inflammation and permeability allowing for translocation of bacteria to the spleen, liver, and pancreas [8]. Normal AMP secretion is important for maintaining a eubiotic environment and healthy SI barrier.

Consumption of probiotics also impacts the microbial environment of the SI. Probiotics can provide 108–1012 colony forming units per day [9]. Assuming 10% survival of 1010 ingested probiotic bacteria, the relative abundance of ingested bacteria compared with resident bacteria in the SI can be 0.01- to 1-fold compared with 0.0001- to 0.00001-fold in the colon [9]. This suggests that probiotics may have a greater impact in the SI than in the colon. Ingested probiotic bacteria support the SI microbiota through cross-feeding and reducing or inhibiting pathogens [9]. However, ingested probiotics are considered transients, as they do not become integral members of the core microbiota [10]. Difficulties in sampling the human SI microbiota limit our knowledge of the relationship between additional factors (i.e., dietary components, medications, lifestyle) and the SI microbiota. Table 1 lists some of the factors affecting the composition of the SI microbiota.
Table 1

Factors that may affect and influence the microbial profile of the small intestine

Nutrient availability



Fermentation substrates

Antimicrobial peptides

Gut motility

Gastric acid, bile, pancreatic enzymes



Resident microbes


Antibiotics or medications


Mucosal health

Small intestine surgery

Disease state

Probiotics (food and dietary supplements)

SI Microbiota Products

Phyla present in the SI (Firmicutes, Bacteroidetes, and Actinobacteria) have the ability to produce B-vitamins through biosynthesis pathways [11•, 12]. It has been estimated that up to 60% of microbes can produce each of the B-vitamins [11•] used by either the human host or other microbiota. A eubiotic microbiome also produces butyrate through fermentation which helps maintains the SI epithelial barrier integrity, promotes villus development, and dampens excessive inflammation [13, 14, 15, 16, 17]. Thus, changes to the SI microbiota composition that directly or indirectly decrease butyrate producers can impact nutrient absorption and gut health of individuals.


Probiotics are of growing interest due to their modulatory effects on markers of human health. Several meta-analyses demonstrate probiotic benefits in modulating symptoms of various GI diseases, such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and Clostridium difficile infections, as well as mood disorders such as depression [18, 19, 20, 21]. Additional meta-analyses have been conducted in order to determine if probiotic efficacy is strain- and disease-dependent [22]. There is strong evidence that probiotics are strain-specific in mitigating symptoms associated with individual diseases [23]. When evaluating a probiotic supplement, the specific strain, the disease, and the individual should be considered, as should results of well-designed human clinical trials.

International consensus states that probiotics exert their benefits to the host by (i) interference with pathogenic bacteria by competing for nutrients and adhesion sites, (ii) improvement of the barrier function of the epithelial lining, (iii) immunomodulation, and (iv) influence on other organs of the body through the immune system and neurotransmitter production [1]. Probiotics also increase the production of vital compounds necessary for eubiosis and human health, including SCFAs such as butyrate [24]. Finally, these beneficial microbes also ensure an intestinal environment where optimal nutrient absorption may occur [24].

Probiotics and the Small Intestine

As stated previously, studying the microbiome of the SI is difficult, as invasive procedures are generally required. Traditional stool samples collected from humans will identify species indigenous to the colon, plus transient bacteria from food, or the oral, esophageal, or SI microbiota. Current understanding of how probiotics influence the SI is largely derived from animal models. Recently, one group administered three probiotic strains, Lactobacillus salivarius G1-1, L. reuteri G8-5, and L. reuteri G22-2, and an antibiotic control to groups of piglets and examined the ileal mucosa proteomics [25]. Piglets consuming the lactobacillus strains had expression of 32, 40, and 27 proteins that are associated with maintaining the integrity of cell structure, cell stability, and pathogen defenses, respectively. Another group administered L. rhamnosus GG (LGG) prophylactically to pigs prior to a Salmonella Infantis challenge [26••]. LGG taken prophylactically downregulated the S. Infantis-induced increase of CD4+ IFNγ+ T cells in Peyer’s patches and IL-7Rα expression in the jejunum, demonstrating a probiotic benefit exerted through the immune system and the complexity of the interactions occurring. Probiotics, specifically LAB, may protect the SI by increasing microbial diversity, upregulating protein expression involved in homeostasis, and maintaining immune system integrity.

SI rotavirus diarrhea and antibiotic-associated diarrhea are both routinely treated with probiotics, particularly LGG [27]. LGG is further able to mechanically protect the mucosa and inhibit the attachment of certain pathogenic bacteria [27].

Probiotics and Intestinal Permeability

A healthy intestinal barrier is selectively permeable, permitting passage of essential nutrients and water while restricting absorption of toxins and pathogens [28]. The TJ, the main regulator of paracelluar permeability, is comprised of transmembrane proteins (claudins), scaffolding proteins (zonulin), and regulatory proteins [29]. Chronic disruption to the gut barrier over time may contribute to GI and autoimmune diseases by stimulating an overactive inflammatory response and may decrease nutrient bioavailability [30]. Probiotics are a potential approach to help maintain the intestinal barrier along the entire intestinal tract. In addition to contributing to butyrate production by a healthy, balanced microbiome, probiotics are effective in strengthening TJ proteins and preserving mucosal integrity, and as such also promote optimal nutrient absorption [31].

One study recently examined the effects of L. reuteri LR1 on intestinal permeability of the SI in weaned pigs [32•]. One hundred forty-four weaned pigs were divided into three intervention groups consisting of a control diet or the same diet plus L. reuteri LR1 or antibiotic treatments for 14 days. When compared with pigs on the antibiotic or control diet, those in the probiotic group had increased villus height to crypt depth ratio and increased TJ protein expression in the mucosa of the jejunum and ileum. Another study administered L. reuteri ZJ617 and LGG by oral gavage to mice who were injected with lipopolysaccharide (LPS) to induce barrier dysfunction [33]. LPS administration caused a reduction in abundance of occludin and claudin-3, and both probiotic strains were able to attenuate the reduction. In another investigation, high doses of kanamycin were administered to disturb the intestinal barrier in mice and study the effects of LAB on Peyer’s patch cells in the ileum [34]. When compared with mice on the control diet, those receiving LAB had increased expression of zonulin-1 and occludin in the ileal tissue. They also had higher levels of serum immunoglobulin A in Peyer’s patch cells, reflecting that Peyer’s patches were protected from kanamycin by LAB. Based on evidence for LAB maintaining barrier integrity observed in recent animal studies, similar studies should be undertaken in humans [35, 36]. The yeast S. boulardii has been shown to be very effective in treatment of clinical disorders with associated intestinal barrier disruption in both animal studies and human clinical trials [2].

Diseases of the Small Intestine and Nutritional Impacts

Small Intestinal Bacterial Overgrowth

Small intestinal bacterial overgrowth (SIBO) has been implicated as a cause of chronic diarrhea and nutrient malabsorption. Estimates of prevalence of SIBO vary based on the testing methods used to diagnose this disease, and many testing methods, such as hydrogen breath tests, are imprecise [37]. Functional GI symptoms of SIBO do not correlate with quantitative SI bacterial culture profiles, but do correlate with dysbiosis as defined by 16S rRNA sequencing of the SI microbiota [38, 39]. Nutrient malabsorption can range from mild to profound, resulting in weight loss and vitamin deficiency–associated neuropathies [37].

Persons with SIBO have between 105 and 106 bacteria/mL luminal content, 2 to 3 log10/mL higher than healthy individuals [40]. The bacterial species contaminating the SI in SIBO patients are commonly identified oropharyngeal and colonic flora, including microaerophilic bacteria such as Streptococcus, Escherichia coli, Staphylococcus, Micrococcus, Klebsiella, and Proteus, and anaerobic bacteria such as Lactobacillus, Bacteroides, Clostridium, Veillonella, Fusobacterium, and Peptostreptococcus [41]. The most commonly prescribed treatment for SIBO is the broad-spectrum antibiotic rifaximin; however, this medication only has a 66.7% cure rate [42, 43]. Rifaximin also has the potential to disturb commensal bacterial populations and induce antibiotic-associated diarrhea and C. difficile infections. Therefore, other therapeutic options such as probiotics to mitigate bacterial overgrowth and repopulate the SI with beneficial bacteria are of interest [44]. Efficacy studies of probiotics in treating SIBO have yielded discordant results [45]. A meta-analysis and systematic review concluded that probiotics were effective at SIBO decontamination and symptom relief, but were ineffective in SIBO prevention [45]. It should be noted that consumption of certain probiotic strains (e.g., Bifidobacterium infantis) may increase methane gas levels suggestive of SIBO in response to the lactulose breath test [46].

Irritable Bowel Syndrome

Discussions about IBS are made difficult by proposed disparate symptomatic subtypes and etiologies [47]. IBS is characterized by abdominal pain associated with altered bowel habits in the form of constipation, diarrhea, or both [48]. SIBO may or may not be present concurrently with IBS. Evidence of a role for SI dysbiosis in IBS is strong, but treatment with probiotics, although yielding promising results, is hampered by not knowing the effectiveness of the specific probiotic strain(s), dose, or necessary duration of treatment [49]. However, treatment with probiotic Bacillus spp. spores reportedly improved measurements of the quality of life of IBS patients, probably owing to modification of the gut microbiota [50]. As with SIBO, altered SI permeability is present in IBS, but only in the diarrhea-predominant subtype [51]. It can safely be concluded that along with permeability changes and associated diarrhea with decreased transit time, nutrient uptake is negatively affected.

Crohn’s Disease

The inflammatory state of Crohn’s disease (CD) can affect SI permeability and reduce nutrient absorption, putting individuals at an increased risk of malnutrition. Immunohistochemical analyses of duodenal biopsies from active CD showed destruction and dilation of TJs compared with controls. This damage coincided with shortening of the microvilli and increased inter-villi distance [52]. Damage to the mucosa, through villi blunting, can limit absorptive capabilities of the SI through loss of brush-border enzymes [53] and reduced surface area.

Nutrient absorption is highly dependent on the action of transporters at the apical surface of epithelial cell membranes. Transcriptional analysis of the ileal mucosa of CD individuals revealed alterations in the expression of 62 solute carrier transporters (SLC) and zinc transporters. The majority of the SLC transporters were downregulated, including those important for amino acid transport. Low levels of transporters and metallothioneins important for the absorption, storage, and export into circulation of zinc was also seen in CD mucosa [54••]. The low expression of the transporters limits the amount of nutrients that enter the enterocyte, ultimately lowering the concentrations in circulation. When the relationship between microbial species and transporter expression was examined by incubating human ileal mucosa with L. casei, only partial recovery of SLC transporter expression was shown [54••]. Although humans are more variable in both ileal microbial composition and physiological processes than an in vitro study, the study provides evidence for a role of intestinal microbiota in CD.

In individuals who have treatment-naïve CD, the SI microbiota is dysbiotic due to a decrease in butyrate producers [55, 56, 57, 58]. The genera Bacteroides and Clostridiales are absent in CD individuals [56•, 58] and negative associations for CD severity were found with lower abundance of the genera: Bacteroides, Faecalibacterium, Roseburia, Blautia, Ruminococcus, and Coprococcus [56•], butyrate producers responsive to probiotic support. Decreased butyrate production could contribute to compromised SI barrier integrity, thus affecting nutrient absorption and increasing inflammation and disease severity. In an in vitro model of CD microbiota, the addition of six butyrate producing bacteria to monolayers of intestinal epithelium cells exposed to CD fecal-derived cultures improved epithelial barrier integrity as measured by transepithelial electrical resistance (TEER) and apparent permeability of the paracellular marker Lucifer yellow [59]. TEER is a widely accepted quantitative technique to measure the integrity of tight junctions in cell culture models of the intestinal epithelium. Colonization capacity in mucus- and lumen-associated CD microbiota was highest when a mixture of butyrate producers was used [59] suggesting that one species alone may not be able to establish within resident microbiota.

A systematic review of 9 studies found little benefit of probiotics in persons with CD [60]. However, many of these studies focused on the use of Bifidobacterium and Lactobacillus. Interestingly, these genera have been found to be at higher concentrations in gut mucosal biopsies in active CD patients [55]. Future probiotic studies should evaluate the use of combination butyrate producers not currently available as dietary supplement probiotics [61].

Nutrition and the Small Intestine Microbiome

Persons with SI diseases that demonstrate malabsorption exhibit distinctive microbiota profiles. A pilot study compared duodenal fluid between children recently diagnosed with IBD to healthy controls [62]. Children with IBD had decreases in total microbial counts of Collinsella, Lactobacillus and Bacillus, Firmicutes, Actinobacteria, and Bacteroidetes. This information is of value as patients with IBD are at risk of malabsorption with micronutrient deficiencies, perhaps related to the dysbiosis observed in the SI [63]. The SI microbiome also dictates how a host will digest and absorb dietary compounds, such as lipids, which may lead to over or under nutrition. One study provided a high-fat diet to germ-free (GF) mice and controls housed under standard conditions and found that GF mice had impaired lipid digestion compared with controls, suggesting an important role for microbiota in digestion/absorption [64].

Other studies have also demonstrated that dietary patterns influence the SI microbiota, which in turn may affect health status. In one study, pigs were fed a diet with a standard concentration of protein (16%), a diet that was moderately reduced in protein diet (13%), or a diet low in protein (10%) for 28 days [65]. Ileal samples were obtained at slaughter for microbiota analysis. Ileal bacteria richness decreased as dietary protein was decreased to 10%; however, TJ protein expression was highest in those receiving the 13% diet. This suggests that a diet that moderately restricted protein intake may actually promote a healthier pattern of ileal bacterial community. Future research may define optimal bacterial communities to promote health and divulge the dietary patterns to build those communities. Other dietary compounds such as sugar substitutes, food additives, and emulsifiers are associated with low microbial diversity and increased inflammation in the SI [66, 67]. Diets rich in polyphenols, fiber, and whole plant sources, however, are associated with increased biodiversity in fecal samples and the upregulation of commensal bacteria in the microbiome [68]. Unfortunately, typical western diets containing processed foods and acellular nutrients are more bioavailable in the SI [69]. This then provides ample nutrients that fuel adverse changes in microbiota composition of the SI [70]. When discussing nutrition and the SI, an interdependent relationship is observed. Beneficial microbes may allow for the optimal absorption and utilization of dietary nutrients while a proper diet will increase microbial diversity and abundances of valuable species to promote efficient nutrient absorption.


The SI is the major site of nutrient absorption, and disruption of normal SI function and integrity can lead to nutritional deficiencies and malnutrition [71, 72]. SI microbiota may be a significant contributor in the development of SI diseases such as SIBO, IBS, and CD, and overt or covert malnutrition. Beneficial microbes produce valuable compounds, such as butyrate, which support proper SI structure and physiology needed to optimally harness nutrients. Therefore, the composition of the SI microbiota plays a substantial role in predicting and influencing human health [73].

Probiotics could help maintain a eubiotic environment, correct dysbiosis, and ameliorate nutrient malabsorption issues within the SI. However, the use of probiotics is complicated as characterization of the SI microbiota in healthy adults, and clinical trials to evaluate probiotic efficacy are relatively scarce, likely due to the invasive sampling procedures required to examine SI contents. Future studies could utilize ex vivo models of SI such as enteroids, 3-dimensional organoids derived from SI stem cells to study probiotic interactions with the SI epithelium [74], and explore new technologies such as robotic sampling capsules to harvest SI microbiota. Non-invasive access to SI luminal contents will improve understanding of SI microbiota’s profile in health and disease and enable more precise studies on the efficacy of probiotics in the SI. Research is also needed to determine efficacy of specific probiotic strains or combinations of strains in therapeutic applications in the SI.

Until new SI lumen sampling methods are available and verified, the use of biomarkers may be the key to determining the status of the SI microbiota, the SI epithelial barrier integrity, and even nutritional status. For example, blood serum analyses for zonulin and bacterial components such as lipopolysaccharide can allude to TJ integrity, and specific cytokines and immunoglobulins can reflect overall immune status of the SI [75]. Additionally, measuring sugar output in the urine is a promising technique that allows researchers to compare site-specific intestinal permeability during various interventions [76].

Eubiosis in the SI creates a homeostatic environment is which the digestive, immune, and endocrine systems collaborate to ensure proper nutrient absorption and utilization. Nutritional status of persons with SI dysbiosis or SI disease should be taken into consideration and probiotics considered as a therapeutic option.



We would like to acknowledge that the first authors, Taylor C. Judkins, and Rebecca J. Solch contributed equally to the paper. Authors Archer and Kramer contributed to microbiological and clinical aspects of the paper, respectively.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


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  1. 1.
    Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, et al. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11:506. Scholar
  2. 2.
    Terciolo C, Dapoigny M, Andre F. Beneficial effects of Saccharomyces boulardii CNCM I-745 on clinical disorders associated with intestinal barrier disruption. Clin Exp Gastroenterol. 2019;12:67–82. Scholar
  3. 3.
    Vancamelbeke M, Vermeire S. The intestinal barrier: a fundamental role in health and disease. Expert Rev Gastroenterol Hepatol. 2017;11(9):821–34. Scholar
  4. 4.
    Bischoff SC, Barbara G, Buurman W, Ockhuizen T, Schulzke J-D, Serino M, et al. Intestinal permeability--a new target for disease prevention and therapy. BMC Gastroenterol. 2014;14:189. Scholar
  5. 5.
    Sender R, Fuchs S, Milo R. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol. 2016;14(8):e1002533. Scholar
  6. 6.
    Press AG, Hauptmann IA, Hauptmann L, Fuchs B, Fuchs M, Ewe K, et al. Gastrointestinal pH profiles in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 1998;12(7):673–8.CrossRefGoogle Scholar
  7. 7.
    Guerra A, Etienne-Mesmin L, Livrelli V, Denis S, Blanquet-Diot S, Alric M. Relevance and challenges in modeling human gastric and small intestinal digestion. Trends Biotechnol. 2012;30(11):591–600. Scholar
  8. 8.
    Ahuja M, Schwartz DM, Tandon M, Son A, Zeng M, Swaim W, et al. Orai1-mediated antimicrobial secretion from pancreatic acini shapes the gut microbiome and regulates gut innate immunity. Cell Metab. 2017;25(3):635–46. Scholar
  9. 9.
    Derrien M, van Hylckama Vlieg JE. Fate, activity, and impact of ingested bacteria within the human gut microbiota. Trends Microbiol. 2015;23(6):354–66. Scholar
  10. 10.
    Zhang C, Derrien M, Levenez F, Brazeilles R, Ballal SA, Kim J, et al. Ecological robustness of the gut microbiota in response to ingestion of transient food-borne microbes. Isme J. 2016;10:2235–45. Scholar
  11. 11.
    • Magnúsdóttir S, Ravcheev D, de Crécy-Lagard V, Thiele I. Systematic genome assessment of B-vitamin biosynthesis suggests co-operation among gut microbes. Front Genet. 2015;6:148. Human gut microbes contain genomic pathways to synthesize B vitamins.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Albert MJ, Mathan VI, Baker SJ. Vitamin B12 synthesis by human small intestinal bacteria. Nature. 1980;283(5749):781–2. Scholar
  13. 13.
    Yan H, Ajuwon KM. Butyrate modifies intestinal barrier function in IPEC-J2 cells through a selective upregulation of tight junction proteins and activation of the Akt signaling pathway. PLoS One. 2017;12(6):e0179586. Scholar
  14. 14.
    Zheng L, Kelly CJ, Battista KD, Schaefer R, Lanis JM, Alexeev EE, et al. Microbial-derived butyrate promotes epithelial barrier function through IL-10 receptor-dependent repression of claudin-2. J Immunol. 2017;199(8):2976–84. Scholar
  15. 15.
    Schulthess J, Pandey S, Capitani M, Rue-Albrecht KC, Arnold I, Franchini F, et al. The short chain fatty acid butyrate imprints an antimicrobial program in macrophages. Immunity. 2019;50(2):432–45.e7. Scholar
  16. 16.
    Sakata T. Stimulatory effect of short-chain fatty acids on epithelial cell proliferation in the rat intestine: a possible explanation for trophic effects of fermentable fibre, gut microbes and luminal trophic factors. Br J Nutr. 1987;58(1):95–103. Scholar
  17. 17.
    Wu W, Xiao Z, An W, Dong Y, Zhang B. Dietary sodium butyrate improves intestinal development and function by modulating the microbial community in broilers. PLoS One. 2018;13(5):e0197762. Scholar
  18. 18.
    Ford AC, Harris LA, Lacy BE, Quigley EMM, Moayyedi P. Systematic review with meta-analysis: the efficacy of prebiotics, probiotics, synbiotics and antibiotics in irritable bowel syndrome. 2018;48(10):1044–60. Scholar
  19. 19.
    Ganji-Arjenaki M, Rafieian-Kopaei M. Probiotics are a good choice in remission of inflammatory bowel diseases: a meta-analysis and systematic review. J Cell Physiol. 2018;233(3):2091–103. Scholar
  20. 20.
    Johnston BC, Lytvyn L, Lo CK, Allen SJ, Wang D, Szajewska H, et al. Microbial preparations (probiotics) for the prevention of Clostridium difficile infection in adults and children: An individual patient data Meta-analysis of 6,851 participants. Infect Control Hosp Epidemiol. 2018;39(7):771–81. Scholar
  21. 21.
    Huang R, Wang K, Hu J. Effect of probiotics on depression: a systematic review and meta-analysis of randomized controlled trials. Nutrients. 2016;8(8):483. Scholar
  22. 22.
    McFarland LV, Evans CT, Goldstein EJC. Strain-specificity and disease-specificity of probiotic efficacy: a systematic review and meta-analysis. Front Med (Lausanne). 2018;5(124).
  23. 23.
    Braga VL, Rocha L, Bernardo DD, Cruz CO, Riera R. What do Cochrane systematic reviews say about probiotics as preventive interventions? Sao Paulo Med J. 2017. Scholar
  24. 24.
    Sánchez B, Delgado S, Blanco-Míguez A, Lourenço A, Gueimonde M, Margolles A. Probiotics, gut microbiota, and their influence on host health and disease. Mol Nutr Food Res. 2017;61(1):1600240. Scholar
  25. 25.
    Su Y, Chen X, Liu M, Guo X. Effect of three lactobacilli with strain-specific activities on the growth performance, faecal microbiota and ileum mucosa proteomics of piglets. J Anim Sci Biotechnol. 2017;8:52. Scholar
  26. 26.
    •• Yang GY, Yu J, Su JH, Jiao LG, Liu X, Zhu YH. Oral administration of Lactobacillus rhamnosus GG ameliorates Salmonella Infantis-induced inflammation in a pig model via activation of the IL-22BP/IL-22/STAT3 pathway. Front Cell Infect Microbiol. 2017;7:323. Proactive administration of probiotics supported the immune system’s ability to defend the host against pathogenic microbes.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Capurso L. Thirty years of Lactobacillus rhamnosus GG: a review. J Clin Gastroenterol. 2019;53(Suppl 1):S1–s41. Scholar
  28. 28.
    Odenwald MA, Turner JR. The intestinal epithelial barrier: a therapeutic target? Nature Reviews Gastroenterology &Amp. Hepatology. 2016;14:9. Scholar
  29. 29.
    Niessen CM. Tight junctions/adherens junctions: basic structure and function. J Investig Dermatol. 2007;127(11):2525–32. Scholar
  30. 30.
    Dignass AU. Mechanisms and modulation of intestinal epithelial repair. Inflamm Bowel Dis. 2001;7(1):68–77. Scholar
  31. 31.
    Rao RK, Samak G. Protection and restitution of gut barrier by probiotics: nutritional and clinical implications. Curr Nutr Food Sci. 2013;9(2):99–107.CrossRefGoogle Scholar
  32. 32.
    • Yi H, Wang L, Xiong Y, Wen X, Wang Z, Yang X, et al. Effects of Lactobacillus reuteri LR1 on the growth performance, intestinal morphology, and intestinal barrier function in weaned pigs. J Anim Sci. 2018;96(6):2342–51. Probiotics maintained growth and structural integrity of small intestine physiology when challenged with an antibiotic.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Cui Y, Liu L, Dou X, Wang C, Zhang W, Gao K, et al. Lactobacillus reuteri ZJ617 maintains intestinal integrity via regulating tight junction, autophagy and apoptosis in mice challenged with lipopolysaccharide. Oncotarget. 2017;8(44):77489–99. Scholar
  34. 34.
    Kim SH, Jeung W, Choi ID, Jeong JW, Lee DE, Huh CS, et al. Lactic acid Bacteria improves Peyer’s patch cell-mediated immunoglobulin a and tight-junction expression in a destructed gut microbial environment. J Microbiol Biotechnol. 2016;26(6):1035–45. Scholar
  35. 35.
    Ren C, Dokter-Fokkens J, Figueroa Lozano S, Zhang Q, de Haan BJ, Zhang H, et al. Lactic acid bacteria may impact intestinal barrier function by modulating goblet cells. Mol Nutr Food Res. 2018;62(6):1700572. Scholar
  36. 36.
    Chen L, Li H, Li J, Chen Y, Yang Y. Lactobacillus rhamnosus GG treatment improves intestinal permeability and modulates microbiota dysbiosis in an experimental model of sepsis. Int J Mol Med. 2019;43(3):1139–48. Scholar
  37. 37.
    Dukowicz AC, Lacy BE, Levine GM. Small intestinal bacterial overgrowth: a comprehensive review. Gastroenterol Hepatol (N Y). 2007;3(2):112–22.Google Scholar
  38. 38.
    Quigley EM, Fried M, Gwee KA, Khalif I, Hungin AP, Lindberg G, et al. World gastroenterology organisation global guidelines irritable bowel syndrome: a global perspective update September 2015. J Clin Gastroenterol. 2016;50(9):704–13. Scholar
  39. 39.
    Saffouri GB, Shields-Cutler RR, Chen J, Yang Y, Lekatz HR, Hale VL, et al. Small intestinal microbial dysbiosis underlies symptoms associated with functional gastrointestinal disorders. Nat Commun. 2019;10(1):2012. Scholar
  40. 40.
    Fine KD, Schiller LR. AGA technical review on the evaluation and management of chronic diarrhea. Gastroenterology. 1999;116(6):1464–86. Scholar
  41. 41.
    Bouhnik Y, Alain S, Attar A, Flourie B, Raskine L, Sanson-Le Pors MJ, et al. Bacterial populations contaminating the upper gut in patients with small intestinal bacterial overgrowth syndrome. Am J Gastroenterol. 1999;94(5):1327–31. Scholar
  42. 42.
    Gatta L, Scarpignato C. Systematic review with meta-analysis: rifaximin is effective and safe for the treatment of small intestine bacterial overgrowth. Aliment Pharmacol Ther. 2017;45(5):604–16. Scholar
  43. 43.
    Barkin JA, Keihanian T, Barkin JS, Antequera CM, Moshiree B. Preferential usage of rifaximin for the treatment of hydrogen-positive small intestinal bacterial overgrowth. Rev Gastroenterol Peru. 2019;39(2):111–5.PubMedGoogle Scholar
  44. 44.
    Grace E, Shaw C, Whelan K, Andreyev HJN. Review article: small intestinal bacterial overgrowth – prevalence, clinical features, current and developing diagnostic tests, and treatment. Aliment Pharmacol Ther. 2013;38(7):674–88. Scholar
  45. 45.
    Zhong C, Qu C, Wang B, Liang S, Zeng B. Probiotics for preventing and treating small intestinal bacterial overgrowth: a meta-analysis and systematic review of current evidence. J Clin Gastroenterol. 2017;51(4):300–11. Scholar
  46. 46.
    Kumar K, Saadi M, Ramsey FV, Schey R, Parkman HP. Effect of Bifidobacterium infantis 35624 (align) on the lactulose breath test for small intestinal bacterial overgrowth. Dig Dis Sci. 2018;63(4):989–95. Scholar
  47. 47.
    Aziz I, Tornblom H, Simren M. Small intestinal bacterial overgrowth as a cause for irritable bowel syndrome: guilty or not guilty? Curr Opin Gastroenterol. 2017;33(3):196–202. Scholar
  48. 48.
    Stanghellini V. Functional dyspepsia and irritable bowel syndrome: beyond Rome IV. Dig Dis (Basel, Switzerland). 2017;35(Suppl 1):14–7. Scholar
  49. 49.
    Principi N, Cozzali R, Farinelli E, Brusaferro A, Esposito S. Gut dysbiosis and irritable bowel syndrome: the potential role of probiotics. J Infect. 2018;76(2):111–20. Scholar
  50. 50.
    Catinean A, Neag AM, Nita A, Buzea M, Buzoianu AD. Bacillus spp. spores-A promising treatment option for patients with irritable bowel syndrome. Nutrients. 2019;11(9). Scholar
  51. 51.
    Dunlop SP, Hebden J, Campbell E, Naesdal J, Olbe L, Perkins AC, et al. Abnormal intestinal permeability in subgroups of diarrhea-predominant irritable bowel syndromes. Am J Gastroenterol. 2006;101(6):1288–94. Scholar
  52. 52.
    Goswami P, Das P, Verma AK, Prakash S, Das TK, Nag TC, et al. Are alterations of tight junctions at molecular and ultrastructural level different in duodenal biopsies of patients with celiac disease and Crohn’s disease? Virchows Arch. 2014;465(5):521–30. Scholar
  53. 53.
    Dunne WT, Cooke WT, Allan RN. Enzymatic and morphometric evidence for Crohn’s disease as a diffuse lesion of the gastrointestinal tract. Gut. 1977;18(4):290–4. Scholar
  54. 54.
    •• Pérez-Torras S, Iglesias I, Llopis M, Lozano JJ, Antolín M, Guarner F, et al. Transportome profiling identifies profound alterations in Crohn’s disease partially restored by commensal bacteria. J Crohn’s Colitis. 2016;10(7):850–9. Dysregulated transporters are found in Crohn’s disease, and beneficial commensal gut bacteria can improve function.CrossRefGoogle Scholar
  55. 55.
    Wang W, Chen L, Zhou R, Wang X, Song L, Huang S, et al. Increased proportions of Bifidobacterium and the Lactobacillus group and loss of butyrate-producing bacteria in inflammatory bowel disease. J Clin Microbiol. 2014;52(2):398–406. Scholar
  56. 56.
    • Gevers D, Kugathasan S, Denson LA, Vazquez-Baeza Y, Van Treuren W, Ren B, et al. The treatment-naive microbiome in new-onset Crohn’s disease. Cell Host Microbe. 2014;15(3):382–92. Mucosal sampling of Crohn’s disease reveals a distrinct microbial profile with a reduction in butyrate producing bacteria.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Wright EK, Kamm MA, Teo SM, Inouye M, Wagner J, Kirkwood CD. Recent advances in characterizing the gastrointestinal microbiome in Crohn’s disease: a systematic review. Inflamm Bowel Dis. 2015;21(6):1219–28. Scholar
  58. 58.
    De Cruz P, Kang S, Wagner J, Buckley M, Sim WH, Prideaux L, et al. Association between specific mucosa-associated microbiota in Crohn’s disease at the time of resection and subsequent disease recurrence: a pilot study. J Gastroenterol Hepatol. 2015;30(2):268–78. Scholar
  59. 59.
    Geirnaert A, Calatayud M, Grootaert C, Laukens D, Devriese S, Smagghe G, et al. Butyrate-producing bacteria supplemented in vitro to Crohn’s disease patient microbiota increased butyrate production and enhanced intestinal epithelial barrier integrity. Sci Rep. 2017;7(1):11450. Scholar
  60. 60.
    Derwa Y, Gracie DJ, Hamlin PJ, Ford AC. Systematic review with meta-analysis: the efficacy of probiotics in inflammatory bowel disease. Aliment Pharmacol Ther. 2017;46(4):389–400. Scholar
  61. 61.
    Langella P, Guarner F, Martín R. Editorial: next-generation probiotics: from commensal bacteria to novel drugs and food supplements. Front Microbiol. 2019;10(1973).
  62. 62.
    Sjöberg F, Barkman C, Nookaew I, Östman S, Adlerberth I, Saalman R, et al. Low-complexity microbiota in the duodenum of children with newly diagnosed ulcerative colitis. PLoS One. 2017;12(10):e0186178. Scholar
  63. 63.
    Taylor L, Almutairdi A, Shommu N, Fedorak R, Ghosh S, Reimer RA, et al. Cross-sectional analysis of overall dietary intake and Mediterranean dietary pattern in patients with Crohn’s disease. Nutrients. 2018;10(11). Scholar
  64. 64.
    Martinez-Guryn K, Hubert N, Frazier K, Urlass S, Musch MW, Ojeda P, et al. Small intestine microbiota regulate host digestive and absorptive adaptive responses to dietary lipids. Cell Host Microbe. 2018;23(4):458–69.e5. Scholar
  65. 65.
    Fan P, Liu P, Song P, Chen X, Ma X. Moderate dietary protein restriction alters the composition of gut microbiota and improves ileal barrier function in adult pig model. Sci Rep. 2017;7:43412. Scholar
  66. 66.
    Nettleton JE, Reimer RA, Shearer J. Reshaping the gut microbiota: impact of low calorie sweeteners and the link to insulin resistance? Physiol Behav. 2016;164(Pt B):488–93. Scholar
  67. 67.
    Chassaing B, Van de Wiele T, De Bodt J, Marzorati M, Gewirtz AT. Dietary emulsifiers directly alter human microbiota composition and gene expression ex vivo potentiating intestinal inflammation. Gut. 2017;66(8):1414–27. Scholar
  68. 68.
    Tuohy KM, Conterno L, Gasperotti M, Viola R. Up-regulating the human intestinal microbiome using whole plant foods, polyphenols, and/or fiber. J Agric Food Chem. 2012;60(36):8776–82. Scholar
  69. 69.
    Tomova A, Bukovsky I, Rembert E, Yonas W, Alwarith J, Barnard ND, et al. The effects of vegetarian and vegan diets on gut microbiota. Front Nutr. 2019;6:47. Scholar
  70. 70.
    Zinocker MK, Lindseth IA. The Western diet-microbiome-host interaction and its role in metabolic disease. Nutrients. 2018;10(3). Scholar
  71. 71.
    Benjamin J, Makharia GK, Kalaivani M, Joshi YK. Nutritional status of patients with Crohn's disease. Indian J Gastroenterol. 2008;27(5):195–200.PubMedGoogle Scholar
  72. 72.
    Fabisiak N, Fabisiak A, Watala C, Fichna J. Fat-soluble vitamin deficiencies and inflammatory bowel disease: systematic review and meta-analysis. J Clin Gastroenterol. 2017;51(10):878–89. Scholar
  73. 73.
    Tuddenham S, Sears CL. The intestinal microbiome and health. Curr Opin Infect Dis. 2015;28(5):464–70. Scholar
  74. 74.
    Blutt SE, Crawford SE, Ramani S, Zou WY, Estes MK. Engineered human gastrointestinal cultures to study the microbiome and infectious diseases. Cell Mol Gastroenterol Hepatol. 2017;5(3):241–51. Scholar
  75. 75.
    Wang L, Llorente C, Hartmann P, Yang A-M, Chen P, Schnabl B. Methods to determine intestinal permeability and bacterial translocation during liver disease. J Immunol Methods. 2015;421:44–53. Scholar
  76. 76.
    Dorshow RB, Johnson JR, Debreczeny MP, Riley IR, Shieh J-J, Rogers TE et al. Noninvasive point-of-care measurement of gastrointestinal permeability. SPIE BiOS SPIE; 2019.Google Scholar

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Authors and Affiliations

  • Taylor C. Judkins
    • 1
  • Douglas L. Archer
    • 1
  • Dean C. Kramer
    • 2
  • Rebecca J. Solch
    • 1
    Email author
  1. 1.Food Science and Human Nutrition DepartmentUniversity of FloridaGainesvilleUSA
  2. 2.GainesvilleUSA

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