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The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.

Antibiotic prophylaxis prior to ERCP for biliary obstruction (February 2024)

For patients with biliary obstruction undergoing endoscopic retrograde cholangiopancreatography (ERCP), the benefit of antibiotic prophylaxis in all versus selected patients is uncertain. In a randomized trial including 378 patients with biliary obstruction undergoing ERCP, antibiotic prophylaxis resulted in lower risk of cholangitis compared with no prophylaxis (2 versus 6 percent) [ 1 ]. Based on these and older data, we reserve antibiotic prophylaxis for patients who are at risk for incomplete biliary drainage with ERCP and await further data before administering antibiotic prophylaxis to all patients with biliary obstruction. (See "Antibiotic prophylaxis for gastrointestinal endoscopic procedures", section on 'Endoscopic retrograde cholangiopancreatography (ERCP)' .)

Pancreatic stenting for preventing pancreatitis after ERCP (February 2024)

Patients with difficult biliary access are at increased risk for pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP), which may be prevented by prophylactic pancreatic stenting. In a trial including 1950 patients at high risk for post-ERCP pancreatitis, individuals assigned to pancreatic stent placement plus indomethacin had lower rates of post-ERCP pancreatitis compared with those assigned to indomethacin alone (11 versus 15 percent) [ 2 ]. Rates of serious adverse events were not significantly different between groups. These data support our approach of prophylactic pancreatic stenting in high-risk patients undergoing ERCP. (See "Management of difficult biliary access during ERCP in adults", section on 'Efficacy' .)

Motorized spiral enteroscopy for evaluating small bowel disorders (October 2023)

Device-assisted enteroscopy facilitates direct access to the small bowel, but studies on motorized spiral enteroscopy are limited. In a trial comparing motorized spiral enteroscopy with single balloon enteroscopy in 110 adults with suspected small bowel disorders, rates of complete small bowel examination were higher with motorized spiral enteroscopy (71 versus 11 percent) [ 3 ]. Motorized spiral enteroscopy also resulted in higher diagnostic yield (80 versus 62 percent) and shorter mean procedure times (58 versus 114 minutes). No major adverse events occurred in either group. These data show promise, but further studies on safety are needed before performing motorized spiral enteroscopy routinely in clinical practice. In addition, its use may be limited by equipment availability and endoscopic expertise. (See "Overview of deep small bowel enteroscopy", section on 'Motorized spiral enteroscopy' .)

ESOPHAGEAL AND GASTRIC DISEASE

Dupilumab for refractory eosinophilic esophagitis (February 2024)

Few data are available on the use of dupilumab (a monoclonal antibody) for treating refractory eosinophilic esophagitis. In a cohort study of 46 patients with refractory eosinophilic esophagitis, dupilumab therapy was associated with histologic remission (defined as <15 eosinophils/high-power field) in 37 patients (80 percent) and with symptomatic improvement in 42 patients (91 percent) after a median of six months [ 4 ]. These data support our approach of using dupilumab for patients with eosinophilic esophagitis who have not responded to other therapies (eg, topical glucocorticoids). (See "Treatment of eosinophilic esophagitis (EoE)", section on 'Dupilumab' .)

Rifabutin triple therapy for Helicobacter pylori (October 2023)

Management of patients who have failed multiple antibiotic regimens for Helicobacter pylori is an increasingly frequent challenge. In a randomized trial in which 364 subjects with H. pylori who failed at least two prior treatments were assigned to rifabutin triple therapy or bismuth quadruple therapy for 14 days, H. pylori eradication rates were similar in both groups [ 5 ]. However, the rifabutin group had a higher compliance rate and a lower rate of adverse effects. This trial supports current guidelines and our recommendation to use rifabutin triple therapy as a salvage treatment for H. pylori. (See "Treatment regimens for Helicobacter pylori in adults", section on 'Salvage regimens' .)

Pyogenic liver abscess and colorectal cancer (February 2024)

Studies from Asia suggest that pyogenic liver abscess is associated with increased incidence of colorectal cancer, but studies outside Asia are scarce. In a 10-year retrospective study from 120 hospitals in the United States, the incidence of colorectal cancer among over 8000 patients with liver abscess was almost fourfold higher during the first six months after diagnosis of liver abscess compared with 23,000 matched controls without liver abscess [ 6 ]. The correlation was not observed among patients whose liver abscess was due to cholangitis or cholecystitis, and the type of organism causing the abscess did not correlate with the incidence of cancer. These findings support prompt screening for colorectal cancer in patients with pyogenic liver abscess, particularly in patients without an underlying hepatobiliary cause. (See "Pyogenic liver abscess", section on 'Association with colorectal cancer' .)

Mortality risk in alcohol-associated liver disease (January 2024)

Few studies have reported the long-term outcomes of patients with alcohol-associated liver disease (ALD). In a national registry study including over 23,000 patients with ALD diagnosed at median age 58 years, 67 percent died during >100,000 person-years of follow-up and liver disease was the primary cause of death in 45 percent [ 7 ]. The 5- and 10-year mortality rates due to liver disease were 26 and 31 percent, respectively. These data emphasize the importance of treating patients with alcohol use disorder and may inform strategies to prevent liver-related mortality in those with ALD. (See "Management of alcohol-associated steatosis and alcohol-associated cirrhosis", section on 'Mortality' .)

Model for End-stage Liver Disease (MELD) 3.0 for liver transplantation (October 2023, Modified December 2023)

The Model for End-stage Liver Disease (MELD) score is used to allocate livers for transplantation. Recently, the Organ Procurement and Transplantation Network implemented an updated score, MELD 3.0, for prioritizing liver transplantation candidates who are ages 12 and older [ 8 ]. MELD 3.0 includes variables from the original model (ie, serum bilirubin, serum creatinine, and international normalized ratio) in addition to other inputs (ie, serum sodium, patient sex, and serum albumin) and a lower creatinine ceiling. Goals of using MELD 3.0 include reducing overall waitlist mortality and improving access for female liver transplant candidates. (See "Model for End-stage Liver Disease (MELD)", section on 'MELD 3.0' . and "Liver transplantation for hepatocellular carcinoma", section on 'MELD 3.0' .)

Paracentesis for hospitalized patients with cirrhosis and ascites (November 2023)

Patients with cirrhosis complicated by ascites are at risk for spontaneous bacterial peritonitis and other complications. However, the magnitude of risk associated with deferring diagnostic paracentesis in such patients when they are hospitalized is uncertain. In a large database study comparing late (ie, ≥24 hours) or no paracentesis with early paracentesis in hospitalized patients with ascites, late paracentesis or no paracentesis was associated with higher risk of acute kidney injury (odds ratio [OR] 2.2 and 1.3, respectively) and inpatient mortality (OR 1.5 and 1.4, respectively) [ 9 ]. These data support performing diagnostic paracentesis within 24 hours of hospital admission, which is consistent with our practice. (See "Diagnostic and therapeutic abdominal paracentesis", section on 'Indications' .)

PANCREATIC AND BILIARY DISEASE

Risk of pancreatic cancer in stable intraductal papillary mucinous neoplasms (November 2023)

The optimal duration of pancreatic cancer surveillance in patients with branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) is unclear. In a study of over 3800 such patients without worrisome features (WFs) or high-risk stigmata (HRS), 42 percent had BD-IPMNs that remained stable in size and did not develop WF/HRS for at least five years [ 10 ]. Within this group, patients ≥75 years with cysts <30 mm and those ≥65 years with cysts <15 mm had a standardized incidence ratio for pancreatic cancer comparable to the general population and low disease-specific mortality. These data suggest that this subgroup may be able to discontinue pancreatic cancer surveillance; however, further studies are needed to validate these results. (See "Intraductal papillary mucinous neoplasm of the pancreas (IPMN): Pathophysiology and clinical manifestations", section on 'Pancreatic malignancy' .)

Microscopic colitis and acute pancreatitis (November 2023)

Microscopic colitis has been associated with several other conditions. In a recent population-based study including >12,000 patients with microscopic colitis, these individuals had a twofold increased risk for acute pancreatitis unrelated to gallstones but no increase in gallstone-related acute pancreatitis compared with matched controls [ 11 ]. The increased risk persisted for more than 10 years after diagnosis. Whether the increase in acute pancreatitis was due to active disease or a side effect of budesonide is unclear. Further studies are needed to evaluate this association. (See "Microscopic (lymphocytic and collagenous) colitis: Clinical manifestations, diagnosis, and management", section on 'Associated conditions' .)

Clinical practice update on exocrine pancreatic insufficiency (November 2023)

The American Gastroenterological Association (AGA) recently published best practice advice on exocrine pancreatic insufficiency (EPI) [ 12 ]. The AGA Clinical Practice Update advises considering a diagnosis of EPI in individuals with moderate-risk clinical conditions (eg, celiac disease, previous intestinal surgery, longstanding diabetes mellitus, Zollinger-Ellison syndrome). It emphasizes the importance of testing for EPI in patients with nonspecific symptoms and cautions against relying on a response to an empiric trial of pancreatic enzymes to diagnose EPI as this may be due to a placebo effect. Our approach is consistent with this guidance. (See "Exocrine pancreatic insufficiency", section on 'Diagnostic approach' .)

SMALL BOWEL AND COLONIC DISEASE

Mirikizumab for moderate to severe ulcerative colitis (August 2023, Modified January 2024)

Therapeutic options for adults with moderate to severe ulcerative colitis (UC) are expanding. In an induction trial comparing mirikizumab (a monoclonal antibody that targets the p19 subunit of interleukin-23) with placebo in nearly 1300 patients, mirikizumab (300 mg intravenously every four weeks) resulted in higher rates of clinical remission after 12 weeks (24 versus 13 percent) [ 13 ]. In the maintenance trial including over 500 patients, mirikizumab (200 mg subcutaneously every four weeks) resulted in higher rates of clinical remission after 40 weeks (50 versus 25 percent). Based on these data, the US Food and Drug Administration approved mirikizumab for moderate to severe UC [ 14 ]. We anticipate using mirikizumab as first- or second-line therapy for adults with moderate to severe UC. (See "Management of moderate to severe ulcerative colitis in adults", section on 'Anti-interleukin antibody-based therapy' .)

Clinical practice update on risk stratification for colorectal cancer screening and postpolypectomy surveillance (December 2023)

The American Gastroenterological Association (AGA) recently published nine statements of best practice advice on risk stratification for colorectal cancer (CRC) screening and postpolypectomy surveillance [ 15 ]. They advise basing risk stratification on an individual's age, a known or suspected predisposing hereditary CRC syndrome, other CRC predisposing conditions (eg, inflammatory bowel disease), and/or a family history of CRC. They also suggest that the decision to continue postpolypectomy surveillance for individuals older than 75 years should be individualized. Shared decision-making discussions should include an assessment of the risks of incident CRC, procedure-related risks, comorbidities, and life expectancy (>5 years). Our approach is consistent with this guidance. (See "Overview of colon polyps", section on 'Risk assessment for subsequent colorectal cancer' .)

Investigational therapy for irritable bowel syndrome with bile acid diarrhea (November 2023)

Patients with irritable bowel syndrome with predominant diarrhea (IBS-D) frequently have concurrent bile acid malabsorption. In a randomized trial in which 31 patients with IBS and bile acid diarrhea were assigned to aldafermin (an investigational analogue of recombinant human fibroblast growth factor 19) or placebo for 28 days, the aldafermin group had lower bile acid synthesis and improved stool consistency during week 4 of treatment, but abdominal pain and stool frequency were not significantly different for the two groups [ 16 ]. Treatment-related adverse events were significantly higher in patients in the aldafermin group, and four patients on aldafermin had a clinically significant increase in low-density lipoprotein cholesterol. More studies are needed to clarify if aldafermin has a role in the treatment of IBS-D. (See "Treatment of irritable bowel syndrome in adults", section on 'Other therapies' .)

Low-dose tricyclic antidepressants in irritable bowel syndrome (October 2023)

The efficacy of tricyclic antidepressants (TCAs) in the management of irritable bowel syndrome (IBS) has not been well established in the primary care setting. In a pragmatic randomized trial, 463 patients with IBS unresponsive to dietary advice and first-line therapies in primary care practices were assigned to titrated low-dose amitriptyline or placebo as a second-line therapy [ 17 ]. At six months, patients treated with low-dose amitriptyline had lower IBS-symptom severity scores and a higher rate of symptom relief. The most common side effects were related to the anticholinergic effects of amitriptyline, but the majority were mild. These data support current guidelines and our recommendation to use TCAs in the management of patients with IBS. (See "Treatment of irritable bowel syndrome in adults", section on 'Antidepressants' .)

Pozelimab for CD55-deficient protein losing enteropathy (October 2023)

Protein-losing enteropathies (PLE) are characterized by excessive loss of serum proteins into the gastrointestinal tract, resulting in hypoproteinemia, edema, and pleural and pericardial effusions. Pozelimab , a C5 inhibitor, has been approved by the US Food and Drug Administration (FDA) to treat patients with CD55-deficient PLE (CHAPLE syndrome) based on an ongoing single-arm phase II/III clinical trial of 10 patients with CHAPLE syndrome and symptomatic hypoalbuminemia [ 18 ]. All patients achieved normalization of albumin by week 12 of treatment with pozelimab and maintained serum albumin concentrations within the normal range through at least 72 weeks. Improvements were also reported in serum IgG levels and total iron-binding capacity. Although FDA approved, long-term safety data are still needed. (See "Protein-losing gastroenteropathy", section on 'Treatment of the underlying disease' .)

OTHER GASTROENTEROLOGY AND NUTRITION

Clinical practice update on bloating and distention (November 2023)

The American Gastroenterological Association (AGA) recently published best practice advice on the evaluation and management of bloating and distention [ 19 ]. The AGA Clinical Practice Update endorses serologic evaluation for celiac disease and exclusion of carbohydrate enzyme deficiencies with dietary restriction and/or breath testing, but emphasizes reserving additional evaluation with abdominal imaging and upper endoscopy for patients with alarm features, recent worsening symptoms, or an abnormal physical examination. Our approach is consistent with this guidance. (See "Overview of intestinal gas and bloating", section on 'Evaluation' .)

• Leem G, Sung MJ, Park JH, et al. Randomized Trial of Prophylactic Antibiotics for Endoscopic Retrograde Cholangiopancreatography in Patients With Biliary Obstruction. Am J Gastroenterol 2024; 119:183.
• Elmunzer BJ, Foster LD, Serrano J, et al. Indomethacin with or without prophylactic pancreatic stent placement to prevent pancreatitis after ERCP: a randomised non-inferiority trial. Lancet 2024; 403:450.
• Rughwani H, Singh AP, Ramchandani M, et al. A Randomized, Controlled Trial Comparing the Total Enteroscopy Rate and Diagnostic Efficacy of Novel Motorized Spiral Enteroscopy and Single-Balloon Enteroscopy in Patients With Small-Bowel Disorders: The Motor Trial (NCT 05548140). Am J Gastroenterol 2023; 118:1855.
• Lee CJ, Dellon ES. Real-World Efficacy of Dupilumab in Severe, Treatment-Refractory, and Fibrostenotic Patients With Eosinophilic Esophagitis. Clin Gastroenterol Hepatol 2024; 22:252.
• Chen J, Guo Y, Huang Y, et al. Rifabutin-Containing Triple Therapy Versus Bismuth Quadruple Therapy for Helicobacter pylori Rescue Treatment: A Multicenter, Randomized Controlled Trial. J Infect Dis 2023; 228:511.
• Suzuki H, Kidder I, Tanaka T, Goto M. Incidence of Colorectal Cancer in Patients Diagnosed With Pyogenic Liver Abscess. JAMA Netw Open 2023; 6:e2348218.
• Kann AE, Jepsen P, Madsen LG, et al. Cause-specific mortality in patients with alcohol-related liver disease in Denmark: a population-based study. Lancet Gastroenterol Hepatol 2023; 8:1028.
• Improvements to MELD, PELD, Status 1A and Status 1B to take effect July 13. United Network for Organ Sharing, 2023. Available at: https://unos.org/news/improvements-to-meld-and-peld-phase-1-data-entry-in-effect-june-15/ (Accessed on September 04, 2023).
• Patel N, Silvey S, O'Leary JG, et al. Early paracentesis is associated with better prognosis compared with late or no-paracentesis in hospitalized veterans with cirrhosis and ascites. Liver Transpl 2023; 29:919.
• Marchegiani G, Pollini T, Burelli A, et al. Surveillance for Presumed BD-IPMN of the Pancreas: Stability, Size, and Age Identify Targets for Discontinuation. Gastroenterology 2023; 165:1016.
• Bergman D, Roelstraete B, Olén O, et al. Microscopic Colitis and Risk of Incident Acute Pancreatitis: A Nationwide Population-Based Matched Cohort Study. Am J Gastroenterol 2023; 118:2041.
• Whitcomb DC, Buchner AM, Forsmark CE. AGA Clinical Practice Update on the Epidemiology, Evaluation, and Management of Exocrine Pancreatic Insufficiency: Expert Review. Gastroenterology 2023; 165:1292.
• D'Haens G, Dubinsky M, Kobayashi T, et al. Mirikizumab as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med 2023; 388:2444.
• Mirikizumab. United States Prescribing Information. Revised November, 2023. US Food & Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761279s000lbl.pdf (Accessed on November 20, 2023).
• Issaka RB, Chan AT, Gupta S. AGA Clinical Practice Update on Risk Stratification for Colorectal Cancer Screening and Post-Polypectomy Surveillance: Expert Review. Gastroenterology 2023; 165:1280.
• BouSaba J, Torres M, Dilmaghani S, et al. Effects of FGF19 Analogue Aldafermin in Patients With Bile Acid Diarrhea: A Randomized, Placebo-Control Trial. Gastroenterology 2023; 165:499.
• Alderson SL, Wright-Hughes A, Ford AC, et al. Amitriptyline at low-dose and titrated for irritable bowel syndrome as second-line treatment (The ATLANTIS trial): protocol for a randomised double-blind placebo-controlled trial in primary care. Trials 2022; 23:552.
• U.S. Food and Drug Administration. FDA approves first treatment for CD55-deficient protein-losing enteropathy (CHAPLE disease). Available at https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-treatment-cd55-deficient-protein-losing-enteropathy-chaple-disease (Accessed on October 23, 2023).
• Moshiree B, Drossman D, Shaukat A. AGA Clinical Practice Update on Evaluation and Management of Belching, Abdominal Bloating, and Distention: Expert Review. Gastroenterology 2023; 165:791.

Emerging Topics in Gastroenterology

Affiliations.

• 1 Department of Family and Community Medicine, University of Kansas School of Medicine-Wichita, 1010 North Kansas, Wichita, KS 67214, USA.
• 2 Department of Family and Community Medicine, University of Kansas School of Medicine-Wichita, 1010 North Kansas, Wichita, KS 67214, USA. Electronic address: [email protected].
• PMID: 29132532
• DOI: 10.1016/j.pop.2017.07.008

The bacteria and fungi in the human gut make up a community of microorganisms that lives in symbiosis with humans, engaging in numerous diverse interactions that influence health. This article outlines the current knowledge on emerging topics in gastroenterology, including microbiome and probiotics, fecal microbiota transplantation, cyclic vomiting syndrome, eosinophilic esophagitis, and microscopic colitis.

Keywords: Cyclic vomiting; Eosinophilic esophagitis; Fecal transplant; Microbiome; Microscopic colitis; Probiotics.

Copyright © 2017 Elsevier Inc. All rights reserved.

Publication types

• Colitis, Microscopic / physiopathology
• Colitis, Microscopic / therapy
• Eosinophilic Esophagitis / physiopathology
• Eosinophilic Esophagitis / therapy
• Fecal Microbiota Transplantation / methods
• Gastroenterology*
• Gastrointestinal Microbiome / physiology
• Primary Health Care
• Probiotics / pharmacology
• Vomiting / physiopathology
• Vomiting / therapy

Supplementary concepts

• Familial cyclic vomiting syndrome

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Articles in 2023

Autism spectrum disorders and the gastrointestinal tract: insights into mechanisms and clinical relevance

Gastrointestinal issues are common in autism spectrum disorders (ASDs). This Review provides a comprehensive overview of the clinical and mechanistic connections between ASDs and gastrointestinal disorders and how these data might be utilized for future research and novel therapeutic targets.

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Neutrophils: from IBD to the gut microbiota

In this Review, Danne and colleagues describe the roles of neutrophils in inflammatory bowel disease, as well as their functions in host–microbiota interactions.

• Camille Danne
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Guidelines for best practices in monitoring established coeliac disease in adult patients

Coeliac disease is a chronic inflammatory disease triggered by gluten consumption in individuals with a genetic susceptibility. These Evidence-Based Guidelines provide recommendations for improving the health care of the patients and discuss future perspectives.

• Daniel Leffler
• David S. Sanders

The maternal gut microbiome in pregnancy: implications for the developing immune system

This Review discusses how the maternal gut microbiome in pregnancy influences the developing immune system and proposes avenues for future research.

• Liza Konnikova
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A new era in obesity management

2023 was the most memorable year on record for obesity. The American Academy of Pediatrics recognized the complex, multifactorial nature of obesity and the broad range of treatments necessary to care for pediatric patients. The first-ever triple agonist and high-potency oral GLP1 agonist was introduced with unprecedented results.

• Fatima Cody Stanford

Novel interventions against alcohol-related liver disease

In 2023, there were significant advancements in trials of interventions to reduce mortality and morbidity from alcohol-related liver disease, spanning the entire spectrum of disease: primary prevention to reduce overall alcohol-related harm, secondary prevention to attenuate fibrosis progression and tertiary prevention using antibiotics for severe alcohol-associated hepatitis.

• Maja Thiele
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Fermented foods and gastrointestinal health: underlying mechanisms

Fermented foods have gained renewed popularity owing to their health-promoting potential. This Review discusses the mechanisms underlying the benefits of fermented foods in gut health and disease, highlighting how specific fermented food microorganisms, food components and bioactive compounds exert their effects. A future outlook on research is also detailed.

• Arghya Mukherjee
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RET signalling controls gut motility

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New options for late-line treatment of metastatic colorectal cancer

Metastatic colorectal cancer is a heterogeneous disease associated with poor patient outcomes. Although the past decade has seen few first-line treatment advances, key studies published in 2023 established new options for late-line therapy of the disease with and without oncogenic drivers, thus expanding the continuum of care in metastatic colorectal cancer.

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Gut microbiota in overweight and obesity: crosstalk with adipose tissue

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Tumour-associated macrophages and pancreatic cancer: an inflammatory loop

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Upgrading therapeutic ambitions and treatment outcomes

Important studies published in 2023 outlined new agents and strategies for the management of inflammatory bowel disease. Therapeutic ambitions for the management of inflammatory bowel disease were raised by the success of combinations of biologic agents in ulcerative colitis and early surgical resection in Crohn’s disease.

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Microbiota-based biomarkers and therapeutics for cancer management

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Role of steatotic liver disease in prediction and prevention of cardiometabolic diseases

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Elafibranor in primary biliary cholangitis

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See the reality again in the field of liver transplantation

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Resmetirom safe for nonalcoholic fatty liver disease

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• v.14(5); 2022 May 27

Global research production pertaining to gastrointestinal involvement in COVID-19: A bibliometric and visualised study

Sa'ed h zyoud.

Department of Clinical and Community Pharmacy, College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine

Poison Control and Drug Information Center, College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine

Clinical Research Centre, An-Najah National University Hospital, Nablus 44839, Palestine. moc.oohay@duoyzdeas

Samah W Al-Jabi

Moyad jamal shahwan.

Department of Clinical Sciences, College of Pharmacy and Health Sciences, Ajman University, Ajman 346, United Arab Emirates

Centre of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman 346, United Arab Emirates

Ammar Abdulrahman Jairoun

Department of Health and Safety, Dubai Municipality, Dubai 67, United Arab Emirates

Corresponding author: Sa'ed H Zyoud, PhD, Associate Professor, Director, Department of Clinical and Community Pharmacy, College of Medicine and Health Sciences, An-Najah National University, Academic Street, Nablus 44839, Palestine. moc.oohay@duoyzdeas

Coronavirus disease 2019 (COVID-19) is a global pandemic that can cause diarrhoea, nausea/vomiting, and abdominal pain, among other gastrointestinal (GI) symptoms.

To perform a bibliometric analysis of the global research production pertaining to GI involvement in COVID-19.

The Scopus database was used to search the global literature on GI involvement in COVID-19 during 2020. A bibliometric review of these publications was also performed using VOSviewer.

Scopus had published 95615 documents on COVID-19 in all areas of research at the time of data collection. In total, 1267 publications on the topic of GI and COVID-19 were identified. Research articles ( n = 606; 47.83%), letters (293; 23.13%), and reviews (186; 14.68%) were the most popular types of documents. The most productive countries and institutions in this field were the United States and Huazhong University of Science and Technology. The most cited paper was Xiao et al , which was published in Gastroenterology as a brief communication, with 798 citations. This paper provides evidence for GI infection of COVID-19 and its possible faecal–oral transmission route. In the term cluster analysis, there were two frontiers in this field: GI manifestations among COVID-19 patients and the implications of COVID-19 for the gastroenterologist.

GI manifestations among COVID-19 patients and implications of COVID-19 for gastroenterologists were of interest, especially in the early stages of the pandemic.

Core Tip: This bibliometric analysis provides the first concise summary of global gastrointestinal (GI) publications related to coronavirus disease 2019 (COVID-19). It highlights the benefits of bibliometric analysis in a systematic and structured way to measure the productivity of studies. GI manifestations among COVID-19 patients and the implications of COVID-19 for gastroenterologists were of interest, especially in the early stage of the pandemic. The results will form the basis for future research and guide decision-making in research related to GI symptoms and treatments in COVID-19.

INTRODUCTION

In December 2019, coronavirus disease (coronavirus disease 2019, COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spread quickly from China to nearly every country in the world, and is now considered the world’s most significant public health threat, causing a massive crisis for global health[ 1 - 3 ]. The 2019 new coronavirus was named SARS-CoV-2 by the World Health Organization (WHO), with COVID-19 being given as the disease name[ 4 ]. As of March 13, 2021, there were over 118 million confirmed cases worldwide, with more than 2.6 million associated global deaths, according to a WHO report[ 5 ].

In most studies, patients with COVID-19 have gastrointestinal (GI) manifestations, such as diarrhoea, nausea, anorexia, vomiting, abdominal pain, and GI bleeding[ 6 - 11 ], in addition to fever and common respiratory symptoms including cough, and shortness of breath[ 3 , 12 ]. However, some patients have developed various fatal complications including severe pneumonia, pulmonary oedema, acute respiratory distress syndrome, septic shock, and organ failure[ 13 - 15 ]. Several studies have shown that SARS-CoV-2 can interact with angiotensin-converting enzyme 2 (ACE2) receptors on ileal enterocytes and colon epithelial cells, implying a trophism for the GI tract[ 7 ]. The pathophysiology of GI symptoms is unclear, but it appears that SARS-CoV-2 binds to ACE2, which regulates amino acid homeostasis and microbiome balance in the intestine, causing a change in physiological function that leads to GI symptoms[ 16 - 18 ].

Several systematic reviews and meta-analyses have indicated that during the pandemic, there was an increase in the number of publications discussing the impact of COVID-19 on the GI system in several countries[ 6 , 9 - 11 , 19 - 27 ]. To date, there has not been a global bibliometric review of research related to GI and COVID-19. Bibliometrics aims to determine the depth of information in a given field[ 28 ]. In other areas of COVID-19, this approach has been used to quantify and categorise research output, allowing for mapping the area in question based on the most involved authors, institutions, countries, citations, journals, and hot topics in this field[ 29 - 32 ]. Therefore, the purpose of this study was to report a bibliometric analysis of the global research production pertaining to GI involvement in COVID-19 to determine the most widely cited papers and most prolific countries, institutions, and journals related to this topic. Our results will help to guide priority setting and policy formulation for long-term strategies to improve the outcomes of COVID-19 patients with GI manifestations.

MATERIALS AND METHODS

Data sources.

The publications were retrieved on the same day from the Scopus on March 20, 2021, to prevent bias due to the daily database updates. Since Scopus is the most commonly accepted and regularly used database for analysing scientific articles in the field of bibliometrics, it was chosen as the search engine. Although we recognise the existence of other databases, we acted in accordance with the methodological approach of previous research[ 33 , 34 ].

Search strategies

The search was restricted to publications between January 1 and December 31, 2020. The following search strategy was used in this bibliometric study to retrieve data.

Step 1: To achieve the goals of this bibliometric review, the terms related to COVID-19 entered into the Scopus engine were chosen from the literature related to COVID-19[ 35 - 38 ]. All of the following terms were used as Article Title/Abstract/Keyword: "COVID 19" OR "2019 novel coronavirus" OR "coronavirus 2019" OR "SARS-CoV-2" OR "SARS-CoV 2" or "coronavirus disease 2019" OR "2019-novel CoV" OR "2019 ncov" OR "COVID 2019" OR "corona virus 2019" OR "nCoV-2019" OR nCoV2019 OR "nCoV 2019" OR 2019-ncov OR COVID-19 OR "Severe acute respiratory syndrome coronavirus 2" OR Novel Coronavirus.

Step 2: We confined the publications that we obtained in Step 1 to those with the terms gastrointestinal and related words in their title. The terms relevant to GI that were entered into the Scopus engine were selected from previous GI meta-analyses[ 6 , 39 ]. All of the following terms were entered as Article Title: gastrointestinal OR "GI tract" OR gastr* OR Diarrh* OR Constipation OR Vomiting OR *intestin* OR dysphagia OR "Abdominal pain" OR Nausea OR heartburn OR Bowel OR Gut OR digest* OR stomach OR duodenal OR colon OR colorectal anorectum. The asterisk (*) was used as a truncator or wildcard to capture all of the term variants that shared a core.

Bibliometric analysis

The data collected included the following bibliometric parameters: type of documents, number of publications, citation count, country, institution, and journals. The impact index per article is presented for the top ten most-cited papers as determined by Reference Citation Analysis (RCA). Baishideng Publishing Group Inc. owns RCA, an open, multidisciplinary citation analysis database (Pleasanton, CA, United States) ( https://www.referencecitationanalysis.com/ ).

Visualise analysis

VOSviewer version 1.6.16 (Leiden University, Leiden, The Netherlands) was used for bibliometric visualisation[ 40 ]. In this study, VOSviewer was used for collaborative patterns between countries and term co-occurrence analysis. As a result, we decided to build and visualise the network terms used in the title/abstract of publications to define the hot topics in this field. The relationship between terms is based on the number of publications in which they appear together, according to co-occurrence analysis[ 40 ]. Therefore, the aim of this study was to identify research areas as hot topics, and it is a valuable indicator for tracking scientific progress[ 41 ].

Volume and types of publications

Scopus had published 95615 documents on COVID-19 in all areas of research at the time of data collection. In total, 1267 publications on the topic of GI and COVID-19 were identified during the period of study (January 1 to December 31, 2020). A total of 1267 documents (1.33%) were used in this study. Research articles ( n = 606; 47.83%), letters (293; 23.13%), and reviews (186; 14.68%) were the most popular types of documents.

Active countries and international research collaboration

The United States was the leader in this field, with 278 publications (21.94%). Other top countries were China (222, 17.52%), Italy (184, 14.52%), and the United Kingdom (159, 12.55%) (Table ​ (Table1). 1 ). Several studies reported the symptoms of GI to be present in 2.6% and 75% patients with COVID 19 infection (Table ​ (Table1). 1 ). There were 33 countries included (the minimum number of publications for each country was 10), and their network collaboration maps were visualised by VOSviewer (Figure ​ (Figure1). 1 ). The top four countries by centrality were the United States, China, Italy, and the United Kingdom. According to their centrality, these countries showed close collaboration with each other and a strong research influence with other countries.

Network visualisation map of international research collaborations among the top 33 active countries with at least 10 articles published each.

List of the top 10 countries pertaining to gastrointestinal publications involvement in coronavirus disease 2019

GI: Gastrointestinal.

Active institutions/organisations

Table ​ Table2 2 shows the top 10 institutions in terms of publication numbers. The Huazhong University of Science and Technology, China ( n = 33 publications), Humanitas Research Hospital, Italy ( n = 23 publications), the Humanitas University, Italy ( n = 30 publications), and the Tongji Medical College, China ( n = 29 publications) were the top four productive and influential institutions, indicating that they have achieved significant scientific achievements and research capability.

List of the top 10 institutions pertaining to gastrointestinal publication involvement in coronavirus disease 2019

Active journals

Regarding journals, Gastroenterology ranked first with 457 publications (4.50%), followed by American Journal of Gastroenterology ( n = 34; 2.68%), Inflammatory Bowel Diseases ( n = 34; 2.68%), and Lancet Gastroenterology and Hepatology ( n = 34; 2.68%). Table ​ Table3 3 presents the top 10 most popular journals with the highest number of global research productions pertaining to GI involvement in COVID-19.

List of the top 10 journals pertaining to gastrointestinal publications involvement in coronavirus disease 2019

Impact factors were retrieved from the 2019 Journal Citation Reports (Clarivate Analytics).

Top cited documents

The number of citations is an important measure of the impact and recognition that a paper has received from the scientific community. Table ​ Table4 4 presents the 10 most cited studies found in the Scopus database. The top 10 most cited publications had citation counts ranging from 269 to 798. Furthermore, the ten most cited articles have an impact index per article of 189 to 617.5 (Table ​ (Table4 4 ).

List of the top 10 cited articles for gastrointestinal publications involvement in coronavirus disease 2019

Most frequent terms (research themes)

Using VOSviewer, we examined the term occurrence from 1267 publications. As seen in Figure ​ Figure2, 2 , 270 words were identified and grouped into two clusters based on the number of times they appeared in the titles and abstracts of all publications. The red cluster involved GI manifestations including terms such as “gastrointestinal”, “symptoms”; “nausea”, “vomiting”, and “diarrhoea”. The green cluster involved implications of COVID-19 for the gastroenterologist including terms such as “recommendations”, "procedure”, “impact”, “surgery”, “endoscopy”, “strategy”, “practice”, and “prevention”.

Network visualisation map of the most frequent terms in titles/abstracts of the retrieved literature pertaining to gastrointestinal publications involvement in coronavirus disease 2019. The terms were divided into two clusters based on the various colours created by default, namely, gastrointestinal manifestations coronavirus disease 2019 (COVID-19) patients (red), and implications of COVID-19 for gastroenterologists (green). The large icon indicates the terms that appeared at a high frequency. Among the 13932 terms, only 270 (defined as terms that occurred > 15 times) appeared in titles and abstracts in all publications.

The use of bibliometric analysis to review the patterns and development of various fields and areas of research is becoming more common. The current data analysis reflects various facets of GI publication involvement in COVID-19, including the top countries, institutions, cited articles, journals generating COVID-19 publications, and hot topics in this field. It is critical to determine scientific output through bibliometric analysis to guide researchers on what has already been developed and what is currently being researched so that future research can resolve information gaps.

Following the COVID-19 pandemic, high-income countries such as the United States, China, Italy, the United Kingdom, Spain, France and Germany are the world leaders in GI publications in COVID-19. A potential reason for these findings is the high prevalence of COVID-19 in countries that experienced the initial outbreak[ 61 - 66 ]. In the most recent studies, nearly 60% of the COVID-19 publications in the Web of Science come from the United States, China, Italy and the United Kingdom[ 67 ]. According to the research, the United States contributed the most scientific papers published during the COVID-19 pandemic. This is due to the fact that it has the most academic journals on the search sites in use, as well as being a country where researchers from all over the world want to publish their findings[ 68 ]. China was second in the ranking. This is demonstrated by the fact that China has over 3.61 million licensed doctors[ 13 ]. Furthermore, Chinese institutions contributed various papers to the COVID-19 research initiative and played a crucial role in the pandemic response[ 69 ].

This study found that many publications focused on GI manifestations among COVID-19 patients and implications of COVID-19 for gastroenterologists. So far, COVID-19-related research has involved disease transmission, virology and immunology, epidemiology, clinical characteristics, nonpharmaceutical interventions, detection and diagnosis, treatment, vaccines, and other categories including the psychological status of the medical staff and public during the pandemic[ 67 , 70 ].

The current study used a bibliometric review to discuss the top 10 cited publications about GI involvement in COVID-19. Just three articles addressed GI intervention in COVID-19 patients, while the rest of the widely cited literature centred on GI characteristics and disease features in COVID-19 patients. The most-cited paper was Xiao et al [ 58 ], which was published in Gastroenterology as a brief communication, with 798 citations. This paper provides evidence for GI infection in COVID-19 and its possible faecal-oral transmission route. The second most-cited paper was by Xu et al [ 59 ] from Nature Medicine as a brief communication. According to the results of that study, rectal swab testing may be more helpful than nasopharyngeal swab testing in assessing the efficacy of management and timing of quarantine termination. However, replication-competent virus in faecal swabs was not demonstrated in the study, and this is necessary to confirm the possibility of faecal-oral transmission. The third most-cited paper was by Gu et al [ 52 ] in Gastroenterology as a commentary, which stated that COVID-19 could be present in the oral cavity and faeces of infected people. Moreover, that study recommended that the initial digestive symptoms of COVID-19 should be an alert for early isolation, detection, diagnosis and intervention.

Therefore, our study provides an understanding of the research on GI symptoms in COVID-19, and citation rates can indicate important research topics, development trends in COVID-19 and GI-related research, and provide a reference for research cooperation. However, the mechanism of intestinal infection, its relationship to cytokine release syndrome, and the probability of faecal-oral transmission all require further research in larger populations, especially prospective validation studies with well-designed questions.

This bibliometric analysis provides the first concise summary of global GI publications related to COVID-19. It highlights the benefits of bibliometric analysis in a systematic and structured way to measure the productivity of studies. However, no search strategy is flawless, and the dropout of false-positive or false-negative results is also expected. We attempted to be as comprehensive as possible, using all terms related to GI and COVID-19 listed in the literature. However, there was a possibility of missing some terms. Therefore, we did our best to retrieve all GI publications concerning COVID-19 and sought to verify their study approach using techniques introduced in previously published bibliometric studies. Furthermore, the number of citations will fluctuate over time due to the rapidly changing existence of COVID-19 science. The final limitation is that the authors did not search all scientific databases; however, this limitation is present in almost all bibliometric studies.

This research offers a detailed overview of the position of GI publications in COVID-19 research evolution during the early stages of the outbreak. In a short timespan (1 year) following the start of the COVID-19 pandemic, high-income countries such as the United States, China, Italy, the United Kingdom, Spain, France and Germany became the global leaders of GI-related publications, and were responsible for the bulk of the literature written in this field. This study has found that many publications focused on GI manifestations among COVID-19 patients and the implications of COVID-19 for gastroenterologists. While GI symptoms play an important role in COVID-19, there are still many knowledge gaps about their pathophysiology and prognostic value. Prospective studies with well-designed questions can be used to perform further research. The results of this bibliometric study will act as a basis for future research and guide decision-makers for research related to GI symptoms and treatment in COVID-19.

ARTICLE HIGHLIGHTS

Research background.

Fever and respiratory symptoms are common in coronavirus disease 2019 (COVID-19) patients. Gastrointestinal (GI) symptoms such as diarrhoea, vomiting, and stomach pain may also occur in some patients.

Research motivation

There was an increase in the number of publications addressing the effect of COVID-19 on the GI system in a variety of countries during the outbreak, according to several systematic reviews and meta-analyses. There has not been a comprehensive bibliometric analysis of research on GI and COVID-19. The aim of bibliometrics is to determine the depth of knowledge in a given area.

Research objectives

The purpose of this study was to report a bibliometric analysis of the global research pertaining to GI involvement in COVID-19 to determine the most widely cited papers and most prolific countries, institutions, and journals related to this topic.

Research methods

We searched Scopus for publications during 2020, and selected articles focused on GI and COVID-19.

Research results

The current data analysis reflects various facets of GI-related publications in COVID-19, including the top countries, institutions, cited articles, journals generating COVID-19 publications, and hot topics in this field. It is critical to determine scientific output through bibliometric analysis to guide researchers on what has already been developed and what is currently being researched so that future research can resolve information gaps.

Research conclusions

COVID-19 GI manifestations and implications for gastroenterologists were of increasing concern, especially in the early stages of the pandemic. As a result, it is suggested that research on this subject be focused on the connection between GI manifestations and potential COVID-19 outcomes.

Research perspectives

Our results will help to guide priority setting and policy formulation for long-term strategies to improve the outcomes of COVID-19 patients with GI manifestations.

Conflict-of-interest statement: The authors have no financial disclosures or conflicts of interest to declare.

PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.

Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

Provenance and peer review: Invited article; Externally peer reviewed.

Peer-review model: Single blind

Peer-review started: March 16, 2021

First decision: May 4, 2021

Article in press: May 7, 2022

Specialty type: Gastroenterology and hepatology

Country/Territory of origin: Palestine

Peer-review report’s scientific quality classification

Grade A (Excellent): 0

Grade B (Very good): B, B

Grade C (Good): C

Grade D (Fair): 0

Grade E (Poor): 0

P-Reviewer: Guo F, China; Song B, China; Wang MK, China S-Editor: Gao CC L-Editor: Kerr C P-Editor: Gao CC

Contributor Information

Sa'ed H Zyoud, Department of Clinical and Community Pharmacy, College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine. Poison Control and Drug Information Center, College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine. Clinical Research Centre, An-Najah National University Hospital, Nablus 44839, Palestine. moc.oohay@duoyzdeas .

Samah W Al-Jabi, Department of Clinical and Community Pharmacy, College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine.

Moyad Jamal Shahwan, Department of Clinical Sciences, College of Pharmacy and Health Sciences, Ajman University, Ajman 346, United Arab Emirates. Centre of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman 346, United Arab Emirates.

Ammar Abdulrahman Jairoun, Department of Health and Safety, Dubai Municipality, Dubai 67, United Arab Emirates.

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Fiber, genes and the gut microbiome: Study reveals possible triggers for inflammatory bowel disease

by University of Michigan

Abdominal pain, diarrhea, weight loss—these and the other symptoms of inflammatory bowel disease (IBD) can be disruptive and debilitating. And while scientists have figured out that IBD has a genetic component, not everyone with a family history develops the disease. To date, the environmental triggers for Crohn's disease and ulcerative colitis, known together as IBD, remain largely unknown.

A new U-M study finds a complex interplay between diet , genes, and the gut microbiota that could explain why IBD develops. Led by the labs of Eric Martens, Ph.D. and Mahesh Desai, Ph.D. and first authors Gabriel Pereira, Ph.D., Marie Boudaud, Ph.D. and their colleagues, the newest study builds on previous work that found that a low fiber diet led to a proliferation of mucin degrading bacteria —bacteria that thrive by eating the mucus lining of the intestine.

In some people, genetic loss of a cytokine—a protein that affects the immune system—known as interleukin-10 (IL-10) or its receptor, leads to the early onset of IBD in infants and children. The new study set out to examine this genetic connection more closely, using mice with the same immune alteration.

While some of these mice spontaneously developed inflammation in their intestinal tracts as well, the level of severity varied and appeared to be made worse by the presence of certain bacteria and a low-fiber diet. In fact, mice bred to lack any bacteria had no evidence of disease.

The team found they could turn up or down inflammation by adjusting the presence or absence of a model human gut microbiome and the dietary fiber content for their mouse models. What's more, the inflammation triggered by fiber-free diets appeared to increase in reaction to the increased abundance of mucin-degrading bacteria Akkermansia mucinphila and Bacteroides caccae.

"These bacteria start foraging on the mucus layer for nutrients, reducing its thickness and barrier function and bringing microbes just 10–100 microns closer to the host tissue. That was enough in the context of the mice with IBD genetics to make them sick," said Martens, professor of microbiology and immunology at U-M Medical School.

Diet effects

On the other hand, feeding the mice a fiber-rich diet prevented inflammation from developing, and even returning mice fed low fiber to a high fiber diet led to a peak in inflammation followed by a decline, suggesting fiber can reverse the deleterious effects of mucus erosion on inflammation.

But ironically, IBD, especially in children, is often treated with a formula-based diet called exclusive enteral nutrition (EEN), which lacks fiber. Despite a lack of fiber, this diet does result in reduced inflammation in people for reasons unexplained.

To answer why, the team dried down the formula to administer it to the mice with IBD genetics. Interestingly, these mice had varying levels of inflammation following the diet, with some experiencing considerably less inflammation than the mice fed the fiber-free diet, even though the EEN diet also reduced mucus thickness.

The team then discovered that elevated amounts of a single branched-chain fatty acid, isobutyrate, were elevated in EEN-fed mice and might suppress inflammation. Isobutyrate is produced through fermentation by some bacteria in the gut. "It seems one of the ways these exclusive enteral nutrition diets could possibly work in people is by triggering certain bacteria to make beneficial metabolites," said Martens.

Spurred by these findings, the team plans to further interrogate how diet and bacteria interact to improve therapies for pediatric IBD, as well as answer how to potentially reverse or prevent the onset of these diseases by manipulation of these environmental triggers.

"Our findings suggest a potential new path for treating IBD. By tailoring specific dietary interventions to influence gut microbiome function, we may be able to manipulate these bacterial communities to alleviate inflammation ," said Pereira.

The research is published in the journal Cell Host & Microbe .

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The Scholarly Kitchen

What’s Hot and Cooking In Scholarly Publishing

The Latest “Crisis” — Is the Research Literature Overrun with ChatGPT- and LLM-generated Articles?

• Artificial Intelligence
• Metrics and Analytics
• Peer Review
• Research Integrity

Elsevier has been under the spotlight this month for publishing a paper that contains a clearly ChatGPT-written portion of its introduction. The first sentence of the paper’s Introduction reads, “Certainly, here is a possible introduction for your topic:…” To date, the article remains unchanged, and unretracted. A second paper , containing the phrase “I’m very sorry, but I don’t have access to real-time information or patient-specific data, as I am an AI language model” was subsequently found , and similarly remains unchanged. This has led to a spate of amateur bibliometricians scanning the literature for similar common AI-generated phrases, with some alarming results . But it’s worth digging a little deeper into these results to get a sense of whether this is indeed a widespread problem, and where such papers have made it through to publication, where the errors are occurring.

Several of the investigations into AI-pollution of the literature that I’ve seen employ Google Scholar for data collection (the link above, and another here ). But when you start looking at the Google Scholar search results, you notice that a lot of what’s listed, at least on the first few pages, are either preprints, items on ResearchGate, book chapters, or often something posted to a website you’ve never heard of with a Russian domain URL. The problem here is that Google Scholar is deliberately a largely non-gated index. It scans the internet for things that look like research papers (does it have an Abstract, does it have References), rather than limiting results to a carefully curated list of reputable publications. Basically, it grabs anything that looks “scholarly”. This is a feature, not a bug, and one of the important values that Google Scholar offers is that it can reach beyond the more limiting inclusion criteria (and often English language and Global North biased) content of indexes like the Web of Science.

But what happens when one does similar searches on a more curated database, one that is indeed limited to what most would consider a more accurate picture of the reputable scholarly literature? Here I’ve chosen Dimensions , an inter-linked research information system provided by Digital Science, as its content inclusion is broader than the Web of Science, but not as unlimited as Google Scholar. With the caveat that all bibliometrics indexes are lagging, and take some time to bring in the most recently published articles (the two Elsevier papers mentioned above are dated as being from March and June of 2024 and so aren’t yet indexed as far as I can tell), my results are perhaps less worrying. All searches below were limited to research articles (no preprints, book chapters, or meeting abstracts) published after November 2022, when ChatGPT was publicly released.

A search for “Certainly, here is” brings up a total of ten articles published over that time period. Of those ten articles, eight are about ChatGPT, so the inclusion of the phrase is likely not suspect. A search for “as of my last knowledge update” gives a total of six articles, again with four of those articles focused on ChatGPT itself. A search for “I don’t have access to real-time data” brings up only three articles, all of which cover ChatGPT or AI. During this same period, Dimensions lists nearly 5.7M research articles and review articles published, putting the error rate for these three phrases to slip through into publications at 0.00007%.

Retraction Watch has a larger list of 77 items (as of this writing), using a more comprehensive set of criteria to spot problematic, likely AI-generated text which includes journal articles from Elsevier, Springer Nature, MDPI, PLOS, Frontiers, Wiley, IEEE, and Sage. Again, this list needs further sorting, as it also includes some five book chapters, eleven preprints, and at least sixteen conference proceedings pieces. Removing these 32 items from the list suggests a failure rate of 0.00056%.

While many would argue that this does not constitute a “crisis”, it is likely that such errors will continue to rise, and frankly, there’s not really any excuse for allowing even a single paper with such an obvious tell to make it through to publication. While this has led many to question the peer review process at the journals where these failures occurred, it’s worth considering other points in the publication workflow where such errors might happen. As Lisa Hinchliffe recently pointed out , it’s possible these sections are being added at the revision stage or even post-acceptance. Peer reviewers and editors looking at a revision may only be looking at the specific sections where they requested changes, and may miss other additions an author has put into the new version of the article. Angela Cochran wrote about how this has been exploited by unscrupulous authors adding in hundreds of citations in order to juice their own metrics. Also possible, the LLM-generated language may have been added at the pageproof stage (whether deliberately or not). Most journals outsource typesetting to third party vendors, and how carefully a journal scrutinizes the final, typeset version of the paper varies widely. As always, time spent by human editorial staff is the most expensive part of the publishing process, so many journals assume their vendors have done their jobs, and don’t go over each paper with a fine toothed comb unless a problem is raised.

Two other important conclusions can be drawn from this uproar. The first is that despite preprints having been around for decades, those both within and adjacent to the research community clearly do not understand their nature and why they’re different from the peer reviewed literature, so more educational effort is needed. It should not be surprising to anyone that there are a lot of rough early drafts of papers or unpublishable manuscripts in SSRN (founded in 1994) or arXiv (launched in 1991). We’ve heard a lot of concern about journalists not being able to recognize that preprints aren’t peer reviewed, but maybe there’s as big a problem much closer to home. The second conclusion is that there seems to be a perception that appearing in Google Scholar search results offers some assurance of credibility or validation. This is absolutely not the case, and perhaps the fault here lies with t he lack of differentiation between the profile service offered by Google Scholar , which is personally curated by individuals and its search results which are far less discriminating.

Going forward, I would hope that at the journals where the small number of papers have slipped through, an audit is underway to better understand where the language was introduced and how it managed to get all the way to publication. Automated checks should be able to weed out common AI language like this, but they likely need to be run at multiple points in the publication process, rather than just on initial submissions. While the systems in place seem to be performing pretty well overall, there’s no room for complacency, and research integrity vigilance will only become more and more demanding.

David Crotty

David Crotty is a Senior Consultant at Clarke & Esposito, a boutique management consulting firm focused on strategic issues related to professional and academic publishing and information services. Previously, David was the Editorial Director, Journals Policy for Oxford University Press. He oversaw journal policy across OUP’s journals program, drove technological innovation, and served as an information officer. David acquired and managed a suite of research society-owned journals with OUP, and before that was the Executive Editor for Cold Spring Harbor Laboratory Press, where he created and edited new science books and journals, along with serving as a journal Editor-in-Chief. He has served on the Board of Directors for the STM Association, the Society for Scholarly Publishing and CHOR, Inc., as well as The AAP-PSP Executive Council. David received his PhD in Genetics from Columbia University and did developmental neuroscience research at Caltech before moving from the bench to publishing.

14 Thoughts on "The Latest “Crisis” — Is the Research Literature Overrun with ChatGPT- and LLM-generated Articles?"

There is a huge difference between an entire article being written by AI, as the title of this post suggests, and having a few paragraphs being written by AI, as the actual evidence in most of this post suggests. I think the most worrisome part of this is that the journal editors are doing such a poor job that they aren’t catching those obvious “certainly…” type phrases, not because of what they imply about authorship, but just because they don’t belong in the final text at all.

I find the debate about using AI and academic integrity is bringing out an inconsistency in our very reasons for opposing “plagiarism”. That is, is the problem that the ideas aren’t yours per se, or that you are “stealing” another person’s ideas? When the “other person” is not a human, suddenly this distinction is in sharp relief. If you aren’t stealing from someone else, is there still a bad thing happening here, or is this just a much more “humanities” version of using R or SPSS to do your quantitative analysis? Usually I find it frustrating when people mix up copyright law with plagiarism, but in this situation I think copyright law has something useful to inform the plagiarism discussion. Copyright law in the US at least is very clear that non-humans (eg monkeys, elephants, and computers) can’t be credited with authorship/creatorship.

• By Melissa Belvadi
• Mar 20, 2024, 7:59 AM
• Reply to Comment

“Also possible, the LLM-generated language may have been added at the pageproof stage…”. That seems a bit far fetched. More likely some manuscripts don’t get carefully reviewed. More interesting to me than including LLM text in low quality articles is the sophistication of AI generated cell biology images. They’re getting to the point that sleuths like Elisabeth Bik can’t tell them from the real thing.

• By Chris Mebane
• Mar 20, 2024, 8:55 AM

The authors of one of the suspect papers have stated that the inclusion of the text was a cut-and-paste error. Why would such an error be “far fetched” during corrections but less so in other parts of the publication process?

• By David Crotty
• Mar 20, 2024, 9:27 AM

This is an interesting discussion; thanks for advancing it. Given the challenges facing scientific and medical publishing, which is a bigger crisis? 1) That overworked, underpaid, stressed, researchers and academics who don’t directly benefit financially from their content are now leveraging AI to speed time to publication, or 2) That the majority of entrenched publishers continue to act as if human friction and delays in getting novel science and groundbreaking medicine to patients and doctors who are trying to improve human suffering, which could be improved significantly with AI, is itself a problem to be dealt with? Full disclosure, I serve as Chief AI Officer of Inizio Medical and am a Founding Board Member of the Society for Artificial Intelligence and Health, but my comment is mine and mine alone.

• By Matt Lewis
• Mar 20, 2024, 9:52 AM

It is alarming that this slipped through after all the work done to tighten up publishing integrity over the last year or two. It suggests more sophisticated fake/fraudulent AI content is also getting through. More generally, it is another embarrassing, public black eye for scholarly publishing and science.

• By Curtis Brundy
• Mar 20, 2024, 10:42 AM

It’s clear from this post that the crisis is not about generative AI, which simply reveals the underlying problem. The real issue is the faulty editorial workflow, which Angela Cochran identified as far back as 2017. The human editor should have the last check of the paper. If you allow authors to make changes, then those changes should be monitored by the editor, and a system such as track changes applied to ensure that any changes the author makes, whether or not requested by the editor, are identifiable for checking.

What this reveals is that scholarly publishing still retains a culture of trust, in this case, trust that the author will not make extensive changes at proof stage. It is no longer possible to run scholarly publishing with the assumption that the author will behave responsibly.

• By Michael Upshall
• Mar 20, 2024, 10:57 AM

I think you’re largely right, but those needs are directly in opposition to the increasing pressure for journals to 1) publish faster, and 2) publish cheaper. As noted in the post, the sorts of human interventions you suggest are the most expensive parts of the process. Would the community accept slower publication and higher APCs/subscription prices in order to ensure this level of scrutiny?

• Mar 20, 2024, 11:00 AM

Well, that’s for the scholarly community to decide, but personally, I don’t think there is a choice, to preserve the credibility of academic publishing.

• Mar 20, 2024, 11:10 AM

What Automated Checks systems do you recommend be used by journals?

• By Deb Whippen
• Mar 20, 2024, 11:24 AM

“Automated” is a loaded word here — every check that I know of requires at least some level of human interpretation and intervention.

That said, there are good recommendations coming out of the STM Research Integrity Hub ( https://www.stm-assoc.org/stm-integrity-hub/ ) and tools include plagiarism checkers, image integrity checkers, and paper mill checkers. As far as I know, there are no reliable automated tools for determining whether text or images were AI-generated. But screening for phrases like the ones mentioned above seems a reasonable step.

And as noted, this makes publishing slower and more expensive.

• Mar 20, 2024, 11:47 AM

As the EIC of a journal, I read every manuscript that is submitted. Lately, I have detected a handful of manuscripts that have the hallmarks of being generated (all or in part) by an LLM. It is fairly obvious (to me) to identify such manuscripts, because the text reads like “word salad”, that is, bland, general sentences that do not seem to converge on a clear meaning and lack specific details. A superficial reading is not good enough in such cases. As pointed out in the post, having actual humans read the manuscripts or proofs is necessary, but expensive.

• By Constance Senior
• Mar 20, 2024, 2:15 PM

Interesting, another question is what percent of peer review reports/peer reviewers are using AI, and is incorrect use of AI in this area able to be detected, I heard this is potentially a growing, and yet somewhat hidden problem as well.

• By Adrian Stanley
• Mar 20, 2024, 4:29 PM

“time spent by human editorial staff is the most expensive part of the publishing process”

It turns out more and more that the most *expensive* part of the publishing process is editorial and other negligence actively encouraged by those who never tire of finding more “cost-effective” and “streamlined/frictionless” ways to “improve the author experience.” It’s a sure way to steer scholarly publishing towards obsolescence because however happy authors (or their administrators) might be for having their work published, fewer and fewer people will be inclined or able to read this work (and AI reading AI-generated or “enhanced” texts is like an empty house of mirrors).

The cost of not having enough human eyes (i.e., editorial staff and peer reviewers) will be (and already is) exorbitant for both science and the public. High-quality, sustainable science and scholarship is slow and tedious and does not respond to exhortations for speed and efficiency. It’s a non-negotiable feature, not a bug.

• Mar 20, 2024, 4:44 PM

The one thing that is absolutely certain is that no copyeditors have been retained for the journals where these articles have slipped through. No proper copyeditor — one who edits for grammar, spelling, clarity, logic, and flow– is going to allow these kinds of things to pass through.

The big platforms do not do proper copyediting; the provide spelling and grammar checking from international outsourcing firms (packagers) and pay them literally one quarter of what I am paid, or they use their production team (layout, not copyeditors) to do the copyedits.

Copyeditors know that the vast majority of the time, we are the first ones to read a manuscript all the way through, after R&R or when there is no peer review. These instances prove that when we aren’t being hired, no one is reading a manuscript from start to finish.

• By Rudy Leon
• Mar 20, 2024, 6:20 PM

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