Larazotide acetate for treatment of celiac disease: A systematic review and meta-analysis of randomized controlled trials

Hoilat, Gilles J.; Altowairqi, Abdulaziz Khalaf; Ayas, Mohamad Fekredeen; Alhaddab, Noor Tariq; Alnujaidi, Razan Abdulkarim; Alharbi, Hadeel Abdulaziz; Alyahyawi, Naseem; Kamal, Aminah; Alhabeeb, Habeeb; Albazee, Ebraheem; Almustanyir, Sami; Abu‐Zaid, Ahmed

doi:10.1016/j.clinre.2021.101782

Cited by 33 publications

(21 citation statements)

References 39 publications

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“…Moreover, the combination of these biomarkers might also be used to follow the progression of the disease severity from pulmonary involvement (serum NSE) to the enhanced systemic inflammation (gut permeability defect and NETosis) and/or the progression into sepsis (presepsin). Additionally, the neutralization of these parameters (alone or in combination)—including (i) the strengthening gut integrity using probiotics, short-chain fatty acid, and/or zonulin alteration [ 103 , 104 ]; (ii) LPS absorption [ 105 ]; and (iii) BG removal [ 106 ]—might be the new adjuvant treatment. Further studies on these topics are required.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil Extracellular Traps in Severe SARS-CoV-2 Infection: A Possible Impact of LPS and (1→3)-β-D-glucan in Blood from Gut Translocation

Saithong

Worasilchai

Saisorn

et al. 2022

Cells

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Due to limited data on the link between gut barrier defects (leaky gut) and neutrophil extracellular traps (NETs) in coronavirus disease 2019 (COVID-19), blood samples of COVID-19 cases—mild (upper respiratory tract symptoms without pneumonia; n = 27), moderate (pneumonia without hypoxia; n = 28), and severe (pneumonia with hypoxia; n = 20)—versus healthy control (n = 15) were evaluated, together with in vitro experiments. Accordingly, neutrophil counts, serum cytokines (IL-6 and IL-8), lipopolysaccharide (LPS), bacteria-free DNA, and NETs parameters (fluorescent-stained nuclear morphology, dsDNA, neutrophil elastase, histone–DNA complex, and myeloperoxidase–DNA complex) were found to differentiate COVID-19 severity, whereas serum (1→3)-β-D-glucan (BG) was different between the control and COVID-19 cases. Despite non-detectable bacteria-free DNA in the blood of healthy volunteers, using blood bacteriome analysis, proteobacterial DNA was similarly predominant in both control and COVID-19 cases (all severities). In parallel, only COVID-19 samples from moderate and severe cases, but not mild cases, were activated in vitro NETs, as determined by supernatant dsDNA, Peptidyl Arginine Deiminase 4, and nuclear morphology. With neutrophil experiments, LPS plus BG (LPS + BG) more prominently induced NETs, cytokines, NFκB, and reactive oxygen species, when compared with the activation by each molecule alone. In conclusion, pathogen molecules (LPS and BG) from gut translocation along with neutrophilia and cytokinemia in COVID-19-activated, NETs-induced hyperinflammation.

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Section: Discussionmentioning

confidence: 99%

Neutrophil Extracellular Traps in Severe SARS-CoV-2 Infection: A Possible Impact of LPS and (1→3)-β-D-glucan in Blood from Gut Translocation

Saithong

Worasilchai

Saisorn

et al. 2022

Cells

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“…For the clinical translation, the evaluation of gut barrier defects in patients with dengue and the strengthening gut integrity (probiotics, short-chain fatty acid, and/or zonulin alteration) (Seo et al, 2021;Hoilat et al, 2022), LPS absorption (Lipcsey et al, 2020), and BG removal (Ohata et al, 2003) might be the interesting adjuvant therapies that attenuate the disease mortality. More studies are warranted.…”

Section: Discussionmentioning

confidence: 99%

Abnormal Blood Bacteriome, Gut Dysbiosis, and Progression to Severe Dengue Disease

Chancharoenthana

Kamolratanakul

Ariyanon

et al. 2022

Front. Cell. Infect. Microbiol.

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Despite a well-known association between gut barrier defect (leaky gut) and several diseases, data on translocation of pathogen molecules, including bacterial DNA (blood bacteriome), lipopolysaccharide (LPS), and serum (1→3)-β-D-glucan (BG), from the gut to the blood circulation (gut translocation) in dengue are still less studied. Perhaps, dengue infection might induce gut translocation of several pathogenic molecules that affect the disease severity. At the enrollment, there were 31 dengue cases in febrile and critical phases at 4.1 ± 0.3 days and 6.4 ± 1.1 days of illness, respectively, with the leaky gut as indicated by positive lactulose-to-mannitol excretion ratio. With blood bacteriome, the patients with critical phase (more severe dengue; n = 23) demonstrated more predominant abundance in Bacteroidetes and Escherichia spp. with the lower Bifidobacteria when compared with the healthy control (n = 5). Meanwhile, most of the blood bacteriome results in dengue with febrile stage (n = 8) were comparable to the control, except for the lower Bifidobacteria in dengue cases. Additionally, endotoxemia at the enrollment was demonstrated in five (62.5%) and 19 (82.6%) patients with febrile and critical phases, respectively, while serum BG was detectable in two (25%) and 20 (87%) patients with febrile and critical phases, respectively. There were higher peripheral blood non-classical monocytes and natural killer cells (NK cells) at the enrollment in patients with febrile phage than in the cases with critical stage. Then, non-classical monocytes (CD14-CD16+) and NK cells (CD56+CD16-) increased at 4 and 7 days of illness in the cases with critical and febrile stages, respectively, the elevation of LPS and/or BG in serum on day 7 was also associated with the increase in monocytes, NK cells, and cytotoxic T cells. In summary, enhanced Proteobacteria (pathogenic bacteria from blood bacteriomes) along with increased endotoxemia and serum BG (leaky gut syndrome) might be collaborated with the impaired microbial control (lower non-classical monocytes and NK cells) in the critical cases and causing more severe disease of dengue infection.

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“…Currently, there are several non-dietary therapies (NDT) in clinical trials. The NDTs of current interest include tight junction integrity (larazotide acetate) [ 105 ], oral enzyme supplements (latiguluinase) [ 106 ], TG2 inhibition [ 107 ], and induction of gluten tolerance with Nexvax2 vaccine [ 108 ].…”

Section: Treatment Of Celiac Diseasementioning

confidence: 99%

“…In a 2021 systematic review and meta-analysis of randomized controlled trials on LA, included four studies comprising 626 patients (465 received LA and 161 given placebo) advocated a good safety profile and superiority of Larazotide over placebo in alleviating GI symptoms in gluten-challenged patients with CD [ 105 ]. This study, as well as previous clinical trials [ 111 , 112 , 113 , 114 ], show that LA significantly reduces GI symptoms, but there are variable results in measured intestinal permeability assessed with urinary lactulose-to-mannitol (LAMA).…”

Section: Treatment Of Celiac Diseasementioning

confidence: 99%

A Comprehensive Review of the Neurological Manifestations of Celiac Disease and Its Treatment

et al. 2022

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Celiac disease (CD) is a common chronic inflammatory disorder occurring in genetically predisposed individuals secondary to gluten ingestion. CD usually presents with gastrointestinal symptoms such as pain, bloating, flatulence, and constipation or diarrhea. However, individuals can present in a nonclassical manner with only extraintestinal symptoms. The neurological manifestations of CD include ataxia, cognitive impairment, epilepsy, headache, and neuropathy. A lifelong gluten-free diet is the current recommended treatment for CD. This review discusses the relevant neurological manifestations associated with CD and the novel therapeutics. Further research is required to get a better understanding of the underlying pathophysiology of the neurological manifestations associated with CD. Clinicians should keep CD in the differential diagnosis in individuals presenting with neurological dysfunction of unknown cause.

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Larazotide acetate for treatment of celiac disease: A systematic review and meta-analysis of randomized controlled trials

Cited by 33 publications

References 39 publications

Neutrophil Extracellular Traps in Severe SARS-CoV-2 Infection: A Possible Impact of LPS and (1→3)-β-D-glucan in Blood from Gut Translocation

Neutrophil Extracellular Traps in Severe SARS-CoV-2 Infection: A Possible Impact of LPS and (1→3)-β-D-glucan in Blood from Gut Translocation

Abnormal Blood Bacteriome, Gut Dysbiosis, and Progression to Severe Dengue Disease

A Comprehensive Review of the Neurological Manifestations of Celiac Disease and Its Treatment

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