Enhancing intestinal transit -
Ideally, it should take between 12 and 24 hours for the food you eat to pass through your GI tract. One of the best ways to slow down the progress of digesting food is to supplement with specific fibers like psyllium and apple pectin.
We recommend Dynamic Fiber at 1 TBSP 2 x a day for a week. Then conduct another beets measurement. You should also keep a food diary and note whether certain foods seem to be causing diarrhea or loose stools.
Obviously, if you are experiencing severe diarrhea or persisting loose stools, you should seek immediate care and talk to your practitioner. You can also take Dynamic Fiber to your tolerance level at a maintenance dose for daily bowel regulation. Note: for some people, fiber supplementation may actually increase transit time speed.
Pay attention to your own individual response. Obviously, you can raise or lower the dose, or discontinue it altogether. If your transit time measured over 24 hours, there are two easy ways to speed it up.
See the instructions below! FYI, Magnesium Citrate supplementation is a relatively simple process. immune support. In the long term, you may need to take maintenance doses of these supplements. However, people usually need higher doses at first to get the bowels moving, and much lower doses in order to maintain a healthy transit time on a daily basis.
Note: a small percentage of people may need to follow both the magnesium citrate and vitamin C recommendations in order to speed up transit time. Take four capsules [ mg] twice a day for three days.
You may notice that you have more frequent stools or that their consistency changes. If you start to have stools that are TOO loose, reduce your Mag Citrate to capsules twice a day.
A week after starting the Mag Citrate, use the beets measurement test again to see if your transit time has improved. If there is still no improvement, increase the dosage to six capsules twice a day. Note: Be VERY careful to keep hydrating and supplementing with electrolytes like Dynamic Hydrate.
Talk to your practitioner before starting the Mag Citrate recommendations in order to get their input on the process and how it may affect you personally. Purchase a high-quality, highly-alkalized, powdered vitamin C such as C Aspa Scorb in order to best affect bowel motility.
When you wake up and before you eat, take mg. Record the time and amount. The transit through the stomach takes between 5 min and 2 h and prolonged exposure to the acidic environment is a huge challenge for the probiotics Cook et al.
In addition, other adverse conditions present in the stomach including ionic strength, enzyme activity pepsin , and mechanical churning have been shown to have an impact on the viability of probiotics Sarao and Arora, ; Surono et al.
For example, the viable cells of Bifidobacterium longum and Bifidobacterium breve became undetectable in simulated gastric juice within an hour Cook et al. After passing through the pylorus, the probiotic bacteria will reach the small intestine where abundant pancreatic juice and bile are present.
Under the neutralizing effect of intestinal fluid, the pH in the small intestine is about 6. However, bile acids and digestive enzymes including lipases, proteases, and amylases can also impact probiotic viability through cell membrane disruption and DNA damage Hamner et al.
In vitro studies have demonstrated that the viability of Lactobacillus salivarius Li01 and Pediococcus pentosaceus Li05 is reduced in simulated intestinal fluid Yao et al. To enhance the tolerance of probiotics to gastric juice and bile in the GIT, the probiotics can be coated with a protective shell, a technique known as microencapsulation.
In recent years, great progress has been made in increasing the survival rate and guaranteeing that sufficient number of viable probiotics reach the colon via microencapsulation-based methods Martin et al.
Probiotics must compete with the host microbiota for nutrients and adhesion sites to be able to colonize the colonic mucosa and proliferate Zmora et al. Due to the colonization resistance, most probiotics are excreted out of the colon with stool after oral administration and shortly after consumption ceases so that the probiotics cannot be detected Sierra et al.
The mechanisms which engender the colonization resistance are illustrated in detailed in the section below. The human body contains a huge microbiome consisting of microorganisms including bacteria, fungi, archaea, viruses, and protozoa Shukla et al.
According to previous studies, each individual contains about 10— trillion symbiotic microbial cells, most of which are bacteria residing in the intestines Gilbert et al.
The gut microbiota plays a symbiotic role during the development of the human body and participates in the process of maintaining health and resisting diseases Fan and Pedersen, In this section, the composition of gut microbiota and the mechanism of colonization resistance will be discussed.
The human gut microbiota consists of more than 1, phylotypes Gilbert et al. In healthy individuals, most phylotypes of bacteria can be roughly classified into Bacteroidetes , Firmicutes , Actinobacteria , Proteobacteria , and Verrucomicrobia Lozupone et al.
Among them, Bacteroidetes and Firmicutes usually dominate the microbiota whereas Actinobacteria , Proteobacteria , and Verrucomicrobia are usually minor constituents. The distribution of bacteria in the intestinal mucosa has certain ecological characteristics.
Along the longitudinal axis of the intestine and colon, the oxygen concentration gradually decreases. More anaerobes such as Clostridium and Faecalibacterium reside in the lower GIT while the upper gastrointestinal tract is enriched in Gram-positive cocci eg, Gemella , Streptococcus Engevik and Versalovic, Along the horizontal axis of the intestine and colon, the antimicrobial molecules and oxygen secreted from the epithelium cells accumulate at high local concentrations within the inner mucus layer, where few microbial inhabitants can colonize Donaldson et al.
The mucus layer in the colon has two different structures: a loose outer layer and a tight inner layer. The former is colonized by Bacteroides acidifaciens , Bacteroides fragilis , Bifidobacteriaceae , and Akkermansia muciniphila which can degrade mucin. The latter is penetrated at low density by a more restricted community including Bacteroides fragilis and Acinetobacter spp.
Donaldson et al. The composition of the gut microbiota is not static. Instead, it is highly variable and its normal variation in diversity is affected by factors including age, genetics, environment, and diet Lozupone et al.
In the early years of life, especially during the first three years, the composition and function of microbes colonized in the intestine are continuously changed until a relatively stable microbial community is established.
Previous studies have shown that the microbiota composition of twins and mother-daughter pairs is more similar than unrelated individuals, suggesting that genetics may play a role in the microbiota composition Dicksved et al.
In contrast, a recent study further showed that the microbiota composition of people living together without kinship had many significant similarities, demonstrating that host genetics had a minor role in determining microbiota composition in this case Rothschild et al.
The microbial composition is considerably different between people in different geographic locations and with different diets, indicating that the gut microbiome is significantly associated with diet and environment Rothschild et al. The normal gut microbiota forms a stable bacterial community that resists the invasion of foreign bacteria and the expansion of pathogens.
The mechanisms of colonization resistance can be divided into two broad categories: direct and indirect mechanisms. Among both categories, direct colonization resistance refers to restriction of exogenous microbial colonization strictly through factors associated with the gut microbiota, independently of any interaction with the host, and includes inhibition and competition for resources Pickard et al.
Indirect colonization resistance is dependent on host-derived factors, including production of antimicrobial peptides, maintenance of the epithelial barrier, and modulation of bile acid concentrations through interaction with host Gibson et al.
For example, bacteriocins are proteinaceous compounds which are synthesized in the ribosomes of both Gram-positive or Gram-negative bacteria and are able to inhibit closely related species or species that utilize similar nutrients or niches Klaenhammer, ; Gibson et al.
It has been found that bacteriocin-producing Enterococcus faecalis can inhibit the colonization of vancomycin-resistant enterococci VRE Kommineni et al.
Probiotics are adversely affected by the colonization resistance exerted by the commensal gut microbiota. Some studies demonstrate that the probiotics which human beings ingest are globally shed in stool in the period confined to the time of administration and shortly thereafter Sierra et al.
Related experiments further demonstrate that probiotics cannot change intestinal microbiota community structure or diversity Kristensen et al. Colonization resistance may be one of the important reasons for the limitation of the long-term effects of probiotics.
Zmora et al. administered a combination consisting of 11 probiotic strains to adult, male specific pathogen-free SPF mice and germ-free GF mice. Stool samples were analyzed at indicated time points, followed by a dissection of the GI tract on day 28 after supplementation.
Significantly higher viable counts of bacteria were observed in GF mice compared to that in SPF groups. An explanation for the results could be that the probiotics encounter a higher degree of mucosal colonization resistance in the SPF mice compared to in the GF mice Zmora et al.
Another interesting study indicated that the efficacy of probiotic colonization varies among different persons.
Successful colonization of the gastrointestinal tract is a key factor for probiotics to be able to exert a sufficient host-interaction to confer health benefits Alp and Kuleasan, Mucosal adhesion is considered a critical step in probiotic colonization; however, the mechanisms of adhesion still require exploring.
In this section, we discuss the composition of the intestinal mucus layer and specific proteins related to probiotic adhesion.
The intestinal mucosa is composed of epithelial layer, lamina propria, and muscularis mucosa. Small intestinal villi, which are formed by the epithelium and lamina propria protruding into the intestinal cavity, cover the surface of the mucosa and are responsible for the absorption of nutrients in the intestine.
The epithelial cells are composed of absorptive cells, goblet cells and endocrine cells. Goblet cells are scattered between absorptive cells, secreting mucus which covers the entire small intestinal cavity, composed of carbohydrates, lipids, salts, protein, bacteria, and cellular debris Ensign et al.
The thickness of mucus varies from approximately 30 to μm; the thickness increases from the intestine to the rectum Van Tassell and Miller, The main proteins are glycoproteins called mucins which polymerize to form a continuous gel matrix, providing a structural basis for the mucosal layer, protecting the intestine from pathogens, enzymes, toxins, dehydration, and abrasion.
At the same time, exogenous nutrients such as vitamins and minerals are present in the intestinal mucus, which provide a huge ecologic growth advantage for bacteria colonized in the intestinal mucus Sicard et al. It can be said that the mucus is an excellent niche for both of probiotics and pathogen.
The process of bacterial adhesion to the mucosa includes reversible and stable stages Kos et al. Initially, probiotics bind to the mucosa through non-specific physical contact, including spatial and hydrophobic recognition, establishing reversible and weak, physical binding Van Tassell and Miller, Subsequently, with the specific interactions between adhesins usually proteins anchored on the cell surface and complementary receptors, probiotics establish a stable binding to the mucus or intestinal epithelial cells IECs , thereby successfully colonizing the GIT Van Tassell and Miller, Probiotics can encode numerous cell-surface factors which are involved in adherence to mucin or IECs.
Buck et al. inactivated and knocked out several specific cell surface factors in the Lactobacillus acidophilus NCFM, including mucin-binding protein Mub , fibronectin-binding protein FbpA , and surface layer protein SlpA.
Significant decrease in adhesion to Caco-2 cells was observed in the each separate protein mutant, showing that the genes which encode FbpA, Mub, and SlpA all contribute to L. acidophilus NCFM adhesion to IECs in vitro Buck et al.
Another similar in vitro study found that mutations in luxS in L. acidophilus NCFM, which encodes autoinducer AI -2, caused a decrease in the adhesion to IECs Buck et al. Additional work demonstrated the involvement of myosin cross-reactive antigen MCRA of L.
salivarius resulted a significant reduction in adhesion to human epithelial cell lines van Pijkeren et al. In addition to the proteins, there are also non-protein molecules present in probiotics, including teichoic acids TA and exopolysaccharides EPS which can interact with host cells to influence the adhesion.
It can be inferred from current publications that there is no fixed molecule that can be applied to all strains of probiotics, despite of the wide range of adhesion-related molecules.
Many adhesins seem to be specie or strain dependent. These adhesion-associated surface molecules of probiotics and mechanisms related to adhesion are discussed in detail below Table 1 and Figure 2. Figure 2 The composition of the mucus layer and association with probiotic surface proteins.
Goblet cells are scattered between absorptive cells, which can secret mucus that cover the entire small intestinal cavity. The mucus is mainly composed of mucins which are rich in cysteine.
The extensive disulfide bonds between mucins form the characteristic viscoelastic properties of mucus. The specific proteins on the surface of probiotics play an important role in probiotic adhesion to mucus.
Mucus-binding proteins for example, can bind to the mucus layer through interactions with glycosyl modifications of mucin. Mucus-binding proteins MUBs are cell surface proteins with a typical signal peptide and C-terminal LPxTG motif in the C-terminus which establish a covalent binding to the bacterial cell wall Juge, MUBs are usually found in lactic acid bacteria, especially Lactobacillus reuteri , which is one of the most dominant probiotic bacteria in the human GIT Roos and Jonsson, ; MacKenzie et al.
MUBs contain multiple Mub repeats Mub domains, ~ residues which share homology to the mucin-binding protein repeats MucBP domains, ~50 residues Mercier-Bonin and Chapot-Chartier, Mub domains can be found in proteins of numerous Lactobacillus spp.
acidophilus , L. plantarum , L. brevis , and L. fermentum Van Tassell and Miller, The amino acid sequence of Mub is highly repetitive and contains two types of related repeats, Mub1 and Mub2. Experiments have also suggested that Mub interacts with carbohydrate components on the mucus, particularly with the glycosylic bond of mucins Van Tassell and Miller, The distribution of MucBP domains in bacterial proteins is more extensive than that of Mub Juge, Similarly, MucBPs in Lactobacillus have been demonstrated to be able to bind to mucus Radziwill-Bienkowska et al.
The extracellular matrix is a complex network of large molecules outside the cells in which the extracellular glycoprotein fibronectin is ubiquitously present. Fibronectin-binding proteins, which are anchored on the bacterial surface, belong to the microbial surface components recognizing adhesive matrix molecules MSCRAMM family of adhesins Schwarz-Linek et al.
It has been shown that fibronectin-binding proteins present on the surface of L. acidophilus can bind to the exposed fibronectin and anchor the IECs Schillinger et al.
Munoz-Provencio et al. showed that purified fibronectin-binding protein, encoded by fbpA of Lactobacillus casei BL23, could bind to immobilized fibronectin. They also observed that mutants with inactivated fbpA showed a lower adhesion rate to immobilized fibronectin Munoz-Provencio et al.
The outermost strata of the bacterial cell wall consist of the surface S- layers, non-covalently bonded semi-porous crystal arrays comprised of self-assembling proteinaceous subunits called S-layer proteins SLPs Sara and Sleytr, The lattices of the S-layer exhibit oblique, square, or hexagonal symmetry when observed with an electron microscope.
Most S-layers are 5 to 25 nm thick and have a molecular weight of almost 40— kDa. S-layers have been found in hundreds of species in almost every taxonomic group of walled bacteria Sleytr et al. S-layers have been shown to be involved in a number of processes including maintaining cell shape, protecting the murein sacculus from lysozyme attack, acting as molecular sieves and antifouling coating, serving as binding sites, and promoting bacterial adhesion Sleytr et al.
SLPs of probiotics also have many benefits to the host. Recent studies found that SLPs purified from Lactobacillus exerted immunomodulatory effects, which attenuated intestinal barrier dysfunction and inflammation, and protected intestinal epithelial barrier Prado Acosta et al.
Surface-layer protein A SlpA is a S-layer protein specifically found in L. acidophilus NCFM. Knockout of SlpA engendered decreased adhesive capability of the bacteria Buck et al.
Ashida et al. compared adhesive capabilities of eight L. acidophilus strains to Caco-2 cells and found that the adhesive capability of L. acidophilus L was highest and that of L.
acidophilus CP23 was lowest among the compared strains Ashida et al. Further research showed that the expression levels of SlpA on the surface of L. acidophilus L was about fold higher than that of L. acidophilus CP23 Ashida et al. In Propionibacterium freudenreichii CIRM-BIA , another protein called surface-layer protein B SlpB , have also been shown to play a key role in adhesion to human intestinal cells.
Significant inhibition of adhesion to HT cells was observed when blocking SlpB with specific antibodies or when inactivating slpB in P. freudenreichii CB do Carmo et al. Johnson et al. identified proteins covalently, co-localized to the outermost stratum of the cell surface within the S-layer of L.
acidophilus NCFM, designated as S-layer associated proteins SLAPs Johnson et al. SLAPs have subsequently been characterized in several Lactobacillus spp.
helveticus , L. crispatus , L. amylovorus , and L. gallinarum Johnson et al. Both SLPs and SLAPs are important mediators of adhesion to host IECs and mucins Buck et al. Interestingly, one of the most prevalent SLAPs in L. acidophilus NCFM, PrtX, acts as a serine protease homolog, and has been shown to be negatively correlated with adhesion in in vitro experiments Johnson et al.
In the study by Johnson et al. the gene prtX , was deleted from the chromosome of L. acidophilus NCFM and it was discovered that the PrtX-deficient strain Δ prtX showed an enhanced cell binding ability to mucin and fibronectin compared to the wild type strain Johnson et al.
More effects of SLPs and SLAPs on the adhesion are still waiting for exploring. Moonlighting proteins are defined as multifunctional proteins which can exhibit more than one biological function Jeffery, Moonlighting proteins including enolase ENO , glyceraldehydephosphate dehydrogenase GAPDH , elongation factor-Tu EF-Tu , and molecular chaperones have been demonstrated to be involved in adhesion of probiotics to human intestinal mucins or IECs Bergonzelli et al.
A more detailed description of the involvement of specific moonlighting proteins in adhesion follows below. Enolase is a multifunctional protein which plays a key role in variety of pathophysiological processes such as glycolysis, fibrinolysis, and DNA transcription Pancholi, As a moonlighting protein, enolase was discovered on the L.
plantarum LM3 and B. bifidum S17 cell surface and it was shown that the protein could bind specifically to the extracellular matrix, thus facilitating the adhesion of bacterial cells to the host Castaldo et al.
Castaldo et al. also compared the differences between wild type strains and mutant strain which carried the enolase null mutation and showed the adhesion ability of mutant strain was less efficient than that of wild strain Castaldo et al. Glyceraldehydephosphate dehydrogenase GAPDH is an enzyme involved in the glycolysis.
GAPDH is considered as a moonlighting protein because it has diverse functions in different processes, including in regulation of apoptosis Hara et al.
GAPDH catalyzes enzymatic reactions mainly in the cytosol. Moreover, it has also been indicated that GAPDH is able to bind the cytoskeletal and extracellular matrix proteins on the cell surface of group B streptococci Seifert et al.
GAPDH lacks an extra-cytoplasmic sorting sequence, and it is interesting how the GAPDH transfers from cytosol to the cell surface Siciliano and Mazzeo, One study showed that L. plantarum LA adheres to human colonic mucin by GAPDH which is expressed on the cell surface Kinoshita et al.
Similarly, Patel et al. acidophilus , and expressed, purified, and obtained a recombinant product r-LaGAPDH. It was discovered that the recombinant protein was in tetramer form in solution, and it showed mucin binding and hemagglutination activity.
Several studies have found that in addition to binding to mucin, GAPDH of L. plantarum also has a highly specific adhesive capacity to plasminogen and fibronectin Sanchez et al.
The stress response of probiotics when exposed to gastric juice and bile will have an effect on the adhesive capacity to mucins and IECs.
Agustina et al. reported that the adhesion of L. paracasei strains to mucin and IECs increased after gastrointestinal acid and bile stress. It is demonstrated that the increased adhesive capacity was attributed to the positive modification of GAPDH biosynthesis Agustina Bengoa et al.
However, bile or acid stress does not always result in increased adhesion capacity. For example, L. delbrueckii subsp. lactis and L. Elongation factor Tu EF-Tu is an intracellular protein which serves several functions in protein synthesis and protein folding, including facilitating protein synthesis and increasing translation accuracy Beck et al.
EF-Tu is comprised of three domains known as domains I, II, and III, forming different sites for binding of guanosine triphosphate GTP and aminoacyl-tRNA Harvey et al. This structure enables EF-Tu to transport aminoacyl-tRNAs to the ribosome during protein synthesis.
Interestingly, EF-Tu is a highly conserved protein which can be found on both cell surfaces of pathogens and probiotics Kunert et al.
The role of EF-Tu on the cell surface involves the processes of bacterial adhesion to host cells, invasion, and immune evasion Ramiah et al. Zhang et al. used 5 M LiCl to remove the surface proteins EF-TU and surface antigen of L.
paracasei and L. After treatment, their adhesion force to HT cells significantly reduced Zhang et al. Nishiyama et al. found that B. longum can release particles into the extracellular environment and relevant proteomics analysis identified several mucin-binding proteins, including EF-Tu Nishiyama et al.
Molecular chaperones are a large class of proteins which facilitate binding and stabilization of unstable conformations of other proteins, and promote correct folding of intracellular proteins Ellis, GroEL is a molecular chaperone which assists the folding of nascent or stress-denatured polypeptides through binding and encapsulation Clare et al.
It has also been indicated in in vitro studies that GroEL plays a critical role in the binding process of L. johnsonii La1 to mucus and intestinal cells in the host environment. Interestingly, the binding process of GroEL to mucins or intestinal cell lines was pH-dependent and the binding capacity varied with the pH; the binding capacity was higher at pH 5.
Small heat shock proteins as ATP-independent chaperones sHsps act by binding unfolding proteins, thereby delaying the formation of harmful protein aggregates Janowska et al. sHSPs contribute to cellular defense against harsh conditions under physiological conditions and the GIT stress responses of most bacteria involving the upregulation of sHSPs Guzzo, ; Haslbeck and Vierling, ; Khaskheli et al.
compared the adhesion ability of 31 L. pentosus strains to mucin and discovered a highly adhesive L. pentosus strain, which over-produced four moonlighting proteins including sHSPs Pérez Montoro et al.
A recent study investigated the impact of knockout of the sHSP genes including HSP1, HSP2, and HSP3 on adhesion of L. plantarum WCFS1 to human enterocyte-like cells, demonstrating that sHSP genes deletion lowered GIT stress resistance and adhesion capacity Longo et al.
Aggregation-promoting factors Apf are secreted proteins which induces self-aggregation and facilitates the maintaining of cell shape. These proteins have mainly been found among Lactobacillus spp. It has been found that Apf-deficient mutants of L.
acidophilus NCFM showed a significant reduction of adherence to Caco-2 cells and mucins compared with the wild type strain, suggesting Apf acts as an adhesion factor which participates in the interaction with the host mucus layer and IECs Goh and Klaenhammer, Similar results have been shown in L.
gasseri SBT Nishiyama et al. Pili are short, straight, and filamentous structures stretching from the cell surface of bacteria. Pili are mostly characterized among Gram-negative bacteria. However, pili-like structures are also found in probiotics like Bifidobacterium spp.
and Lactobacillus spp. Alp and Kuleasan, Unlike those in Gram-negative bacteria, these pili have a narrow diameter ~1—10 nm and every pilus consists of multiple pilin subunits which are coupled to each other covalently Kankainen et al. Lankainen et al. discovered three LPXTG-like pilins SpaCBA in L.
rhamnosus GG LGG Kankainen et al. Each of the three pilins has its own location and function in the pilus: backbone SpaA for length, basal SpaB for anchoring, and tip SpaC for adhesion Kant et al. Study showed the adhesion to human intestinal mucus was destroyed by SpaC antibody and blocked in a mutant of LGG which carried the inactivated SpaC gene, demonstrating the SpaC is essential in the interaction with mucus Kankainen et al.
Subsequently, another type of LGG pilus called SpaFED was phenotypically characterized. Similar to SpaCBA, SpaFED pilus can also mediate the adhesion to mucin Rintahaka et al.
With a better understanding of the mechanisms of chronic constipation and continued advances in pharmaceutical development, an expanding array of treatment approaches have been developed.
At present, drugs are the mainstay for patients with chronic constipation. Many studies have reported the efficacy and safety of laxatives in patients with constipation.
The main categories of approved drugs for the treatment of constipation are osmotic laxatives, stimulant laxatives, secretagogues, serotonergic agents, and ileal bile acid transporter inhibitors Black and Ford, Drugs used for the treatment of chronic constipation are listed in Table 1.
However, different drugs act via different pathways, and a further understanding of their mechanisms, combined with that of ion transport and the expression of AQPs, may lead to the development of promising drugs. The American Gastroenterological Association recommends that use of a fiber supplement should be the initial treatment approach for constipation Bharucha et al.
Fiber is composed of high-molecular weight food components that cannot be degraded by intestinal enzymes thus it remains in the intestinal cavity and increases fecal volume. Insoluble fibers, such as wheat bran, may alter gut motility, thereby accelerating gastrointestinal transit and increasing the frequency of stools.
Soluble fiber, such as psyllium, expands after absorbing water in the intestine, thus softening and increasing the volume of feces. Although fiber supplements are effective in the treatment of constipation, adverse reactions, such as bloating, are becoming a problem with long-term therapy Wald et al.
If patients do not respond to fiber, then osmotic laxatives should be considered. Osmotic laxatives are poorly absorbed or non-absorbed substances, that produce intraluminal osmotic gradients, causing secretion of water and electrolytes into the lumen.
This results in luminal water retention, an increase in stool water content and stool softening, thus facilitates stool passage Krogh et al.
These treatments are useful for patients with mild-to-moderate constipation, and the main side effects are diarrhea and abdominal distention. As an osmotic laxative, lactulose has osmotic activity and can attract water to the colon cavity Jouët et al. Since it is harmless to the human body and can effectively regulate the physiological rhythm of the colon, it is widely used to treat constipation in the elderly, pregnant women, and children.
Adverse reactions are limited to the gastrointestinal system, with bloating and abdominal pain being the most common. Polyethylene glycol is a non-absorbable macromolecule belonging to the group of osmotic laxatives.
Its mechanism of action is physical; it acts through local infiltration, retaining water in the colon cavity, thus softening feces, increasing fecal volume, and leading to unobstructed defecation.
Polyethylene glycol can improve constipation-related symptoms such as stool frequency and stool consistency Chassagne et al. Clinical studies have found that low-dose polyethylene glycol is significantly better than lactulose in improving constipation symptoms, with fewer adverse reactions Attar et al.
Polyethylene glycol can be used for the symptomatic treatment of constipation in children aged 6 months and older and in adults. Salt laxative MgSO 4 can increase the intestinal osmotic pressure, prevent the absorption of water in the colon, increase the intestinal contents, and stimulate intestinal peristalsis, resulting in rapid and severe catharsis.
The increased cAMP concentration subsequently leads to the activation of PKA, which promotes CREB phosphorylation and AQP3 gene transcription Ikarashi et al. Excessive use of salt laxatives may induce electrolyte disorders and are therefore, not suitable for the elderly and patients with decreased kidney-function.
If the patient does not respond to osmotic laxatives, stimulant laxatives are recommended. Stimulant laxatives stimulate the intestinal mucosa and nerve plexus to secrete water and electrolytes, resulting in peristaltic contraction, thereby accelerating colonic transport.
Stimulant laxatives are effective, and their side effects are known. Chronic use of stimulant laxatives does not seem to cause tolerance or rebound constipation. However, common side effects include diarrhea and abdominal pain Wald, Bisacodyl stimulates the secretion and motility of the small intestine and colon via the following mechanisms: increased secretion of TNF-α and prostaglandin E 2 PGE 2 in the colon following the oral administration of bisacodyl.
TNF-α and PGE 2 , as paracrine factors, act on the colonic mucosal epithelial cells resulting in an immediate reduction in AQP3 expression, thus exerting their laxative effects Ikarashi et al.
In a 4-weeks trial, oral bisacodyl was reported to be safe and well-tolerated Kamm et al. However, bisacodyl is associated with abdominal cramps and diarrhea. Secretagogues are second-line drugs, the effects of which are similar to those of osmotic laxatives. Secretagogues act directly on intestinal epithelial cells, increasing fluid secretion into the intestinal cavity, thereby changing the consistency of stools and reducing the transit time in the colon Luthra et al.
However, these drugs are associated with side effects such as diarrhea when used clinically. Lubiprostone is a prostaglandin E 1 derivative, which can activate the intestinal chloride channel type 2 on the apical surface of small intestinal enterocytes, thereby reducing epithelial permeability and promoting intestinal fluid secretion.
Additionally, sodium and water enter the intestinal cavity passively, increasing the secretion of fluid in the intestinal cavity Gonzalez-Martinez et al. Lubiprostone can significantly increase stool frequency, improve stool consistency, and reduce straining, which makes it effective for the treatment of constipation Nishii et al.
The results of a meta-analysis showed that adverse reactions such as nausea, vomiting, and diarrhea were common incidence rate, 2. This may be related to the rapid flow of fluid into the small intestine after taking the medicine.
Plecanatide and Linaclotide are GC-C receptor agonists that target GC-C receptors on the lumen of the intestinal epithelium, resulting in increased intestinal fluid secretion Shah et al. By activating colonic epithelial GC-C receptors, the synthesis of intracellular and extracellular cGMP is increased Busby et al.
Intestinal dilatation caused by increased intestinal fluid can promote intestinal movement, and therefore treat constipation. The reported efficacy of plecanatide and linaclotide is similar, and the most common side effect is diarrhea Bassotti et al.
Furthermore, increased cGMP can regulate abdominal pain Silos-Santiago et al. The use of osmotic and stimulant laxatives, either alone or in combination, may be considered in first-line drug therapy. Second-line agents, such as prucalopride are indicated in patients with an inadequate response or poor tolerance to a first-line drug.
Studies have reported that exploiting epithelial targets with nonabsorbable serotonergic agents could provide safe and effective therapies. Serotonin agonists stimulate intestinal secretion and motility by activating 5-HT receptors in the gastrointestinal nervous system.
Unlike other older non-selective 5-HT 4 receptor agonists e. Prucalopride is a high-affinity 5-HT 4 receptor agonist with colonic prokinetic activity Vijayvargiya and Camilleri, Prucalopride functions by activating 5-HT 4 receptors in myenteric plexus neurons and stimulates HAPCs to increase colonic motility Miner et al.
This significantly increases intestinal muscle contraction, as well as stool frequency and consistency in patients with chronic constipation. Some studies have also found that prucalopride can increase the expression of c-kit mRNA in colonic tissue of rats with constipation, and then improve the function of ICCs, so as to promote colonic motility.
It is effective at improving stool frequency, stool consistency and straining. The most common side effects include diarrhea, headache, nausea, and abdominal pain Daniali et al. Multicenter, double-blind, randomized, placebo-controlled trials have demonstrated that prucalopride is superior to placebo in the short to medium term and can improve constipation in both men and women across a broad spectrum of ages and ethnicities Camilleri et al.
Nevertheless, this drug is considerably more expensive than conventional therapy. With knowledge that 5-HT 3 receptors can participate in the activation of propulsive motility and secretory responses in the gut, 5-HT 3 agonists have been developed and tested for the treatment of constipation Mawe and Hoffman, Bile acid can activate the secretory activity of colonic epithelial cells Mekjian et al.
Therefore, up-regulation of the colonic bile acid concentration can be used to treat patients with constipation. Bile acid, a natural laxative in the human body, has garnered attention for the treatment of chronic constipation because of its ability to promote colonic epithelial secretion Keely et al.
However, its efficacy and safety need to be further confirmed in large scale studies. Elobixibat can block the enterohepatic circulation of bile acid, up-regulate the synthesis of bile acid reaching the colon, and stimulate the secretion of fluid and electrolytes, thereby increasing fecal water content and gut motility Mekjian et al.
Increased gut motility facilitates stool passage. Few adverse reactions have been associated with this drug and they include abdominal pain and diarrhea. Abdominal pain with elobixibat may be related to its ability to induce dilatation and contraction Taniguchi et al. As a motilin receptor agonist, mitemcinal GM can stimulate and promote peristalsis of the gastrointestinal tract by acting on the motilin receptor Sudo et al.
This effect has been observed in animal models; however, due to a lack of clinical outcome data, the clinical significance of these studies has not been clearly demonstrated. Therefore, further clinical trials are required to confirm the efficacy and safety of mitemcinal in this population Mozaffari et al.
Probiotic consumption can regulate the intestinal microbiota of patients with constipation, which in turn, can improve gut motility. Some studies have shown that probiotics can be helpful for treating patients with constipation improved stool frequency and stool consistency with very few side effects Ohkusa et al.
These studies have mainly involved the bacteroides , bifidobacterial, and lactobacilli. Recently, the positive impacts of SCFAs on gut motility and constipation were established Chu et al.
Nevertheless, since the effects of probiotics may be strain-specific and the exact mechanism of action remains unknown, more studies and randomized controlled trials are needed to confirm the effects of probiotics in patients with constipation Dimidi et al.
Traditional Chinese Medicine TCM has a role in promoting gastrointestinal motility and has been used to treat constipation for more than 1, years in China. In recent years, there have been many reports about TCM in the treatment of constipation and the improvement of gastrointestinal function Cirillo and Capasso, Therefore, TCM has garnered increasing attention as a promising alternative treatment for constipation.
However, few studies have investigated its therapeutic mechanisms. Thus, the long-term efficacy and side-effect profiles of these medicines in modern medicine need to be determined.
Further studies are needed to determine the exact mechanism for the observed recovery of intestinal function. Importantly, the composition of TCM is complex. Senna and rhubarb are anthraquinone laxatives used widely in the treatment of intestinal constipation.
Sennoside A exerts a laxative effect through its main bioactive component. Rheinanthrone, the active metabolite of sennoside A, can increase the production of PGE 2 Kon et al. Owing to its toxicity to the kidney and liver, we suggest that special attention should be paid to patients with kidney and liver diseases when using Senna drugs for a long period Cao et al.
Total glucosides of paeony TGP are extracted from the root of Paeonia Lactiflora Pall. Studies have shown that TGP can improve the function of ICCs, block inhibitory neurotransmitters such as NO, NOS, and VIP, and increase the fecal volume and water content, as well as intestinal transit rate Zhu et al.
As a common disease that seriously impacts the quality of life and mental health of patients, chronic constipation has attracted widespread attention.
Further studies on the abnormal changes of the ENS, ANS, CNS, endocrine signaling, and microbiota would aid our understanding of constipation from the perspective of gut motility. Intestinal fluid and electrolyte transport are also strongly correlated with chronic constipation.
As a subject for future research, ion channels and AQPs play critical roles in the transport of fluid. At present, studies on ion transport and AQPs in constipation are limited, and many complex mechanisms have not been clarified.
Further experiments are warranted to demonstrate this mechanism. With extended symptom duration, severity, and frustration, the occurrence of additional symptoms will also increase. Therefore, patients with chronic constipation usually require active treatment. The choice of therapeutic drugs should focus on the effectiveness of relieving the symptoms of constipation, the improvement of the intestinal environment, and the effectiveness and safety of long-term use.
If these measures fail, prescription laxatives with different mechanisms of action may be used. Modifying the gut luminal environment through gut motility, fluid, and electrolytes will affect transit and secretion in the gut, thereby benefiting patients with chronic constipation.
Intestinal fluid transport mediated by ion channels and AQPs is the key mechanism through which many laxatives exert their effects. Nevertheless, further studies are still required to resolve the problem. Recently, the action of probiotics on gut motility was shown to be beneficial for constipation.
However, the positive effects of probiotics depend on the specific probiotics used and the level applied. Therefore, the use of probiotics in the treatment of chronic constipation is promising and further studies are required.
We hope that a better understanding of the pathogenesis of constipation and the mechanism of drug action may create new targets for the treatment of diseases that remain a major scourge worldwide. Y-YC and Y-PT conceived and designed the review. QZ searched the literature and drafted the manuscript.
D-QX and S-JY additions and revisions in manuscript. JY and L-MX examined the literature and made the figures. R-JF edited the manuscript. Y-YC and Y-PT made a critical revision of the review. All authors approved the final version of the manuscript. This work was supported by the National Natural Science Foundation of China , Cultivation Plan of Young Scientific and Technological Stars in Shaanxi Province , The Youth Innovation Team of Shaanxi Universities , Natural Science Foundation of Shaanxi Provincial Department of Education 17jk , and Subject Innovation Team of Shaanxi University of Chinese Medicine YL The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.
Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Ahmed, M. Functional, Diagnostic and Therapeutic Aspects of Gastrointestinal Hormones. CrossRef Full Text Google Scholar. Attar, A.
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Knowledge Nutrition myths and truths power, and Enhancing intestinal transit your bowel transit time can empower you to improve your digestion and elimination functions. Ideally, it should Enhancing intestinal transit between Engancing and transut hours for the food you eat to pass through your GI tract. One of the best ways to slow down the progress of digesting food is to supplement with specific fibers like psyllium and apple pectin. We recommend Dynamic Fiber at 1 TBSP 2 x a day for a week. Then conduct another beets measurement.Video
Best Supplement For SIBO \u0026 Fixing Gut Motility?Enhancing intestinal transit -
But you don't have to stick to these two modalities if they aren't your thing. Here are some other types of exercise you can try:. Basic movement, like walking, speeds up digestion by stimulating the muscles 3 in your stomach and small intestine, helping move things along.
Walking any time of the day is great, but a post-prandial stroll may be especially beneficial. Research suggests 4 that taking a 15 minute, leisurely walk right after eating can help move food through your stomach more quickly. The keyword here is leisurely , though.
Going too hard can have the opposite effect. There are many yoga poses , like dandasana, janu sirsasana, and even savasana that can help speed up your digestion. Committing to a simple minute sequence each day can physically support digestive processes and encourage elimination.
Yoga can also indirectly speed up digestion by promoting relaxation. When you're relaxed, your nervous system is in a parasympathetic state. This calming state, aptly nicknamed "rest and digest," is critical for proper digestion.
Some foods, like refined carbohydrates we're looking at you, sugar and anything fried, impede digestion, while others keep things moving as they should.
Take a look at your plate and make sure these things are on it:. Probiotic-rich foods , or fermented foods, are teeming with good bacteria that support your gut health. Research in 5 Applied and Environmental Microbiology 5 suggests 5 that yogurt—one of the go-to probiotic foods—can speed up digestion, while also supporting the part of the immune system that lives in your gut known as the GALT.
If you don't do dairy, or you just like options, you can, and should, also try kimchi, natto, kefir, pickled vegetables, miso, tempeh, and sauerkraut FYI: Just 2 tablespoons of raw sauerkraut contain about 1 million colony-forming units [CFUs] of good bacteria.
In addition to a diet rich in gut-supporting foods, a well-formulated probiotic supplement can also be a very helpful option. Fiber is another nonnegotiable for digestion.
There are two main types—soluble and insoluble—and while you should get both for overall health, insoluble fiber is the star of the show when it comes to transit time. Pay special attention to prebiotic fibers , too.
These types of fibers, which you can get from a variety of sources like garlic, onions, leeks, Jerusalem artichoke, and jicama, serve as a food source for probiotics, helping them grow and colonize the gut.
And don't forget to actually chew your food read: Don't just chomp a couple of times and then swallow. Failing to take in optimal amounts of hydration 7 can affect digestion, so it's impossible to keep things moving without drinking plenty of fluids.
But that doesn't mean an extra cup of coffee or a sugary lemonade. Stick to these beneficial liquids:. Water is the most essential nutrient you put into your body.
It helps you digest your food and absorb nutrients , and then push the waste through your digestive system. Drinking enough water is a surefire way to support digestion, so make sure you're getting what you need daily 9 cups for women and Herbal teas can help nourish your gut, but certain varieties have benefits beyond that.
Dandelion tea 8 , for example, has been shown to stimulate muscle contractions and help push food through the digestive system, while fennel 9 and senna 10 teas have a stronger laxative-type effect. Bone broth is a double whammy for digestion.
Not only does it keep your gut hydrated, but it also contains gelatin and gut-supporting minerals, electrolytes, and bioactives, like calcium, magnesium , phosphorus, chondroitin sulfate, and glucosamine.
Stay away from drinking too much caffeine, though. Sluggish digestion is really uncomfortable, but there are plenty of practical things you can do to speed things up.
Filling your plate with fermented and fiber-rich foods, drinking plenty of noncaffeinated fluids, and regularly moving your body especially after a big meal are great places to start.
Skip to Content. Shop Health Coaching Classes Editor's Picks Beauty Food Healthy Weight Login Login. Similarly, MucBPs in Lactobacillus have been demonstrated to be able to bind to mucus Radziwill-Bienkowska et al.
The extracellular matrix is a complex network of large molecules outside the cells in which the extracellular glycoprotein fibronectin is ubiquitously present. Fibronectin-binding proteins, which are anchored on the bacterial surface, belong to the microbial surface components recognizing adhesive matrix molecules MSCRAMM family of adhesins Schwarz-Linek et al.
It has been shown that fibronectin-binding proteins present on the surface of L. acidophilus can bind to the exposed fibronectin and anchor the IECs Schillinger et al. Munoz-Provencio et al. showed that purified fibronectin-binding protein, encoded by fbpA of Lactobacillus casei BL23, could bind to immobilized fibronectin.
They also observed that mutants with inactivated fbpA showed a lower adhesion rate to immobilized fibronectin Munoz-Provencio et al. The outermost strata of the bacterial cell wall consist of the surface S- layers, non-covalently bonded semi-porous crystal arrays comprised of self-assembling proteinaceous subunits called S-layer proteins SLPs Sara and Sleytr, The lattices of the S-layer exhibit oblique, square, or hexagonal symmetry when observed with an electron microscope.
Most S-layers are 5 to 25 nm thick and have a molecular weight of almost 40— kDa. S-layers have been found in hundreds of species in almost every taxonomic group of walled bacteria Sleytr et al.
S-layers have been shown to be involved in a number of processes including maintaining cell shape, protecting the murein sacculus from lysozyme attack, acting as molecular sieves and antifouling coating, serving as binding sites, and promoting bacterial adhesion Sleytr et al.
SLPs of probiotics also have many benefits to the host. Recent studies found that SLPs purified from Lactobacillus exerted immunomodulatory effects, which attenuated intestinal barrier dysfunction and inflammation, and protected intestinal epithelial barrier Prado Acosta et al.
Surface-layer protein A SlpA is a S-layer protein specifically found in L. acidophilus NCFM. Knockout of SlpA engendered decreased adhesive capability of the bacteria Buck et al. Ashida et al. compared adhesive capabilities of eight L. acidophilus strains to Caco-2 cells and found that the adhesive capability of L.
acidophilus L was highest and that of L. acidophilus CP23 was lowest among the compared strains Ashida et al. Further research showed that the expression levels of SlpA on the surface of L. acidophilus L was about fold higher than that of L. acidophilus CP23 Ashida et al.
In Propionibacterium freudenreichii CIRM-BIA , another protein called surface-layer protein B SlpB , have also been shown to play a key role in adhesion to human intestinal cells.
Significant inhibition of adhesion to HT cells was observed when blocking SlpB with specific antibodies or when inactivating slpB in P. freudenreichii CB do Carmo et al. Johnson et al. identified proteins covalently, co-localized to the outermost stratum of the cell surface within the S-layer of L.
acidophilus NCFM, designated as S-layer associated proteins SLAPs Johnson et al. SLAPs have subsequently been characterized in several Lactobacillus spp. helveticus , L. crispatus , L. amylovorus , and L.
gallinarum Johnson et al. Both SLPs and SLAPs are important mediators of adhesion to host IECs and mucins Buck et al. Interestingly, one of the most prevalent SLAPs in L. acidophilus NCFM, PrtX, acts as a serine protease homolog, and has been shown to be negatively correlated with adhesion in in vitro experiments Johnson et al.
In the study by Johnson et al. the gene prtX , was deleted from the chromosome of L. acidophilus NCFM and it was discovered that the PrtX-deficient strain Δ prtX showed an enhanced cell binding ability to mucin and fibronectin compared to the wild type strain Johnson et al.
More effects of SLPs and SLAPs on the adhesion are still waiting for exploring. Moonlighting proteins are defined as multifunctional proteins which can exhibit more than one biological function Jeffery, Moonlighting proteins including enolase ENO , glyceraldehydephosphate dehydrogenase GAPDH , elongation factor-Tu EF-Tu , and molecular chaperones have been demonstrated to be involved in adhesion of probiotics to human intestinal mucins or IECs Bergonzelli et al.
A more detailed description of the involvement of specific moonlighting proteins in adhesion follows below. Enolase is a multifunctional protein which plays a key role in variety of pathophysiological processes such as glycolysis, fibrinolysis, and DNA transcription Pancholi, As a moonlighting protein, enolase was discovered on the L.
plantarum LM3 and B. bifidum S17 cell surface and it was shown that the protein could bind specifically to the extracellular matrix, thus facilitating the adhesion of bacterial cells to the host Castaldo et al.
Castaldo et al. also compared the differences between wild type strains and mutant strain which carried the enolase null mutation and showed the adhesion ability of mutant strain was less efficient than that of wild strain Castaldo et al.
Glyceraldehydephosphate dehydrogenase GAPDH is an enzyme involved in the glycolysis. GAPDH is considered as a moonlighting protein because it has diverse functions in different processes, including in regulation of apoptosis Hara et al.
GAPDH catalyzes enzymatic reactions mainly in the cytosol. Moreover, it has also been indicated that GAPDH is able to bind the cytoskeletal and extracellular matrix proteins on the cell surface of group B streptococci Seifert et al.
GAPDH lacks an extra-cytoplasmic sorting sequence, and it is interesting how the GAPDH transfers from cytosol to the cell surface Siciliano and Mazzeo, One study showed that L. plantarum LA adheres to human colonic mucin by GAPDH which is expressed on the cell surface Kinoshita et al.
Similarly, Patel et al. acidophilus , and expressed, purified, and obtained a recombinant product r-LaGAPDH. It was discovered that the recombinant protein was in tetramer form in solution, and it showed mucin binding and hemagglutination activity. Several studies have found that in addition to binding to mucin, GAPDH of L.
plantarum also has a highly specific adhesive capacity to plasminogen and fibronectin Sanchez et al. The stress response of probiotics when exposed to gastric juice and bile will have an effect on the adhesive capacity to mucins and IECs.
Agustina et al. reported that the adhesion of L. paracasei strains to mucin and IECs increased after gastrointestinal acid and bile stress. It is demonstrated that the increased adhesive capacity was attributed to the positive modification of GAPDH biosynthesis Agustina Bengoa et al.
However, bile or acid stress does not always result in increased adhesion capacity. For example, L. delbrueckii subsp. lactis and L. Elongation factor Tu EF-Tu is an intracellular protein which serves several functions in protein synthesis and protein folding, including facilitating protein synthesis and increasing translation accuracy Beck et al.
EF-Tu is comprised of three domains known as domains I, II, and III, forming different sites for binding of guanosine triphosphate GTP and aminoacyl-tRNA Harvey et al.
This structure enables EF-Tu to transport aminoacyl-tRNAs to the ribosome during protein synthesis. Interestingly, EF-Tu is a highly conserved protein which can be found on both cell surfaces of pathogens and probiotics Kunert et al.
The role of EF-Tu on the cell surface involves the processes of bacterial adhesion to host cells, invasion, and immune evasion Ramiah et al. Zhang et al. used 5 M LiCl to remove the surface proteins EF-TU and surface antigen of L. paracasei and L. After treatment, their adhesion force to HT cells significantly reduced Zhang et al.
Nishiyama et al. found that B. longum can release particles into the extracellular environment and relevant proteomics analysis identified several mucin-binding proteins, including EF-Tu Nishiyama et al.
Molecular chaperones are a large class of proteins which facilitate binding and stabilization of unstable conformations of other proteins, and promote correct folding of intracellular proteins Ellis, GroEL is a molecular chaperone which assists the folding of nascent or stress-denatured polypeptides through binding and encapsulation Clare et al.
It has also been indicated in in vitro studies that GroEL plays a critical role in the binding process of L. johnsonii La1 to mucus and intestinal cells in the host environment. Interestingly, the binding process of GroEL to mucins or intestinal cell lines was pH-dependent and the binding capacity varied with the pH; the binding capacity was higher at pH 5.
Small heat shock proteins as ATP-independent chaperones sHsps act by binding unfolding proteins, thereby delaying the formation of harmful protein aggregates Janowska et al. sHSPs contribute to cellular defense against harsh conditions under physiological conditions and the GIT stress responses of most bacteria involving the upregulation of sHSPs Guzzo, ; Haslbeck and Vierling, ; Khaskheli et al.
compared the adhesion ability of 31 L. pentosus strains to mucin and discovered a highly adhesive L. pentosus strain, which over-produced four moonlighting proteins including sHSPs Pérez Montoro et al.
A recent study investigated the impact of knockout of the sHSP genes including HSP1, HSP2, and HSP3 on adhesion of L. plantarum WCFS1 to human enterocyte-like cells, demonstrating that sHSP genes deletion lowered GIT stress resistance and adhesion capacity Longo et al. Aggregation-promoting factors Apf are secreted proteins which induces self-aggregation and facilitates the maintaining of cell shape.
These proteins have mainly been found among Lactobacillus spp. It has been found that Apf-deficient mutants of L. acidophilus NCFM showed a significant reduction of adherence to Caco-2 cells and mucins compared with the wild type strain, suggesting Apf acts as an adhesion factor which participates in the interaction with the host mucus layer and IECs Goh and Klaenhammer, Similar results have been shown in L.
gasseri SBT Nishiyama et al. Pili are short, straight, and filamentous structures stretching from the cell surface of bacteria. Pili are mostly characterized among Gram-negative bacteria.
However, pili-like structures are also found in probiotics like Bifidobacterium spp. and Lactobacillus spp. Alp and Kuleasan, Unlike those in Gram-negative bacteria, these pili have a narrow diameter ~1—10 nm and every pilus consists of multiple pilin subunits which are coupled to each other covalently Kankainen et al.
Lankainen et al. discovered three LPXTG-like pilins SpaCBA in L. rhamnosus GG LGG Kankainen et al. Each of the three pilins has its own location and function in the pilus: backbone SpaA for length, basal SpaB for anchoring, and tip SpaC for adhesion Kant et al.
Study showed the adhesion to human intestinal mucus was destroyed by SpaC antibody and blocked in a mutant of LGG which carried the inactivated SpaC gene, demonstrating the SpaC is essential in the interaction with mucus Kankainen et al.
Subsequently, another type of LGG pilus called SpaFED was phenotypically characterized. Similar to SpaCBA, SpaFED pilus can also mediate the adhesion to mucin Rintahaka et al. Meyrand et al. detected one adhesion-associated pilin on the surface of L. lactis which was plasmid-encoded, suggesting the possibility of spread of adhesion effect among L.
lactis through horizontal gene transfer Meyrand et al. Type Via pili, type IVb tight adherence Tad pili, and sortase-dependent pili have been found in the genomes of almost Bifidobacterium spp.
bifidum , B. breve , B. longum , and B. adolescentis , and have been demonstrated to play important roles in the adhesion to IECs or the extracellular matrix Westermann et al. A recent study showed that acid stress could enhance the adhesion ability of GG to intestine epithelium through the induction of pili-related genes including spaC and spaF Bang et al.
Exopolysaccharides EPS are surface carbohydrate polymers existing in most bacteria and fungi. They have various bioactivities functions, including lowering cholesterol, immunomodulating, anti-oxidation, anti-virus, counteract colonization of enteropathogens, and anti-coagulant Fanning et al.
As a protective surface layer, EPS play a positive role in helping probiotics enhance the tolerance to harsh condition of GIT by forming biofilms and communicating with other microorganisms or with host cells Arena et al.
However, there has been no conclusive conclusions so far about whether EPS can promote adhesion. According to existing references, EPS can not only participate in the adhesion process, but also reduce the adhesion efficiency of probiotics. Since the EPS on the probiotic surface, especially those with high molar mass and large volume, may shield other adhesion proteins.
One previous report estimated the adhesive properties of several lactic acid bacteria LAB strains to Caco-2 cells, and found EPS may facilitate probiotic adhesion Garcia-Ruiz et al. The effect of EPS on bacterial adhesion seems to be dependent on probiotic specie and strain.
A previous study investigated three EPS depletion mutant strains of L. Lp90 mutant strain showed improved adhesion to Caco-2 cells compared to the Lp90 wild-type strain. Interestingly, the depletion of EPS genes for WCFS1 and SF2A35B strains did not influence their mucoadhesion Lee et al.
For B. animalis , higher proportion of high molecular weight of EPS showed lower mucoadhesion, indicating that different EPS on bacterial surface might confer variable adhesion characteristics Castro-Bravo et al. Although the contribution of EPS to the probiotic colonization process is controversial, it can be confirmed that the presence of EPS plays a significant role in the interaction of probiotics with the host.
Teichoic acids TAs are important components of the Gram-positive bacterial cell wall, which are composed of alditol phosphate repeating units, contributing to the hydrophobic character and electrostatic charge of the bacterial cell surface Arena et al. TA can be divided into lipotheicoic acid LTA and wall teichoic acid WTA.
In early s, the role of both TA on binding to host cells was raised Beachey, ; Aly et al. One study found that LTA could inhibit the adhesion of L. johnsonii La1 to Caco-2 cells in a concentration-dependent way Granato et al.
We discussed various unfavorable conditions which influence the viability and mucoadhesion of probiotics during GI transit. Colonization of probiotics on the mucus layer could be achieved when adhesive proteins from each side bind together, on the premise of overcoming the colonization resistance.
Thus, the characteristics and functions of different proteins of were specifically reviewed. However, most of current research on mucoadhesion-related molecules of probiotics are limited to lactic acid bacteria.
Adhesive proteins and mucoadhesion mechanisms of probiotics such as Bifidobacterium, Enterococcus, Pediococcus are still waiting for exploring. Besides, how probiotics communicate with commensal bacteria and some are successfully introduced to gut microbiota is also of great interest.
Understanding these factors will facilitate the employment of effective delivery strategies designed for probiotics to overcome colonization resistance and achieve health benefits.
SH developed the idea of the manuscript, drafted the manuscript, and edited the manuscript. YL, JX, and YF helped with the figures and the table. BB, ZL, and LXL revised the manuscript. ZW and JL developed the idea of the manuscript, drafted the outline, and revised the manuscript.
MY and LJL organized and edited the manuscript. All authors contributed to the article and approved the submitted version. This work was supported by the National Key Research and Development Program of China YFC and National Natural Science Foundation of China The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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