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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Nutr.</journal-id>
<journal-title>Frontiers in Nutrition</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Nutr.</abbrev-journal-title>
<issn pub-type="epub">2296-861X</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fnut.2025.1658150</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Nutrition</subject>
<subj-group>
<subject>Original Research</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>The combined use of vitamin B1 and vitamin B12 accelerates the recovery of gastrointestinal function after rectal cancer surgery</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes" equal-contrib="yes">
<name>
<surname>Tang</surname>
<given-names>Song</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="corresp" rid="c001"><sup>&#x002A;</sup></xref>
<xref ref-type="author-notes" rid="fn0003"><sup>&#x2020;</sup></xref>
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<contrib contrib-type="author" equal-contrib="yes">
<name>
<surname>Luo</surname>
<given-names>Simin</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<xref ref-type="author-notes" rid="fn0003"><sup>&#x2020;</sup></xref>
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<contrib contrib-type="author" equal-contrib="yes">
<name>
<surname>Fang</surname>
<given-names>Weikun</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="author-notes" rid="fn0003"><sup>&#x2020;</sup></xref>
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<contrib contrib-type="author">
<name>
<surname>Chen</surname>
<given-names>Zhenyu</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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<contrib contrib-type="author">
<name>
<surname>Liao</surname>
<given-names>Yongfang</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
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<contrib contrib-type="author">
<name>
<surname>Cai</surname>
<given-names>Huiqiang</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>4</sup></xref>
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<contrib contrib-type="author" corresp="yes">
<name>
<surname>Zhang</surname>
<given-names>Weibin</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="corresp" rid="c001"><sup>&#x002A;</sup></xref>
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<contrib contrib-type="author" corresp="yes">
<name>
<surname>Chen</surname>
<given-names>Dan</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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<aff id="aff1"><sup>1</sup><institution>Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangdong Pharmaceutical University</institution>, <addr-line>Guangzhou, Guangdong</addr-line>, <country>China</country></aff>
<aff id="aff2"><sup>2</sup><institution>Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University</institution>, <addr-line>Guangzhou, Guangdong</addr-line>, <country>China</country></aff>
<aff id="aff3"><sup>3</sup><institution>Department of Surgery, The First Affiliated Hospital of Guangdong Pharmaceutical University</institution>, <addr-line>Guangzhou, Guangdong</addr-line>, <country>China</country></aff>
<aff id="aff4"><sup>4</sup><institution>Department of General Surgery, Dianbai District People&#x2019;s Hospital</institution>, <addr-line>Maoming, Guangdong</addr-line>, <country>China</country></aff>
<author-notes>
<fn fn-type="edited-by" id="fn0001">
<p>Edited by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/2325896/overview">John Le</ext-link>, University of Alabama at Birmingham, United States</p>
</fn>
<fn fn-type="edited-by" id="fn0002">
<p>Reviewed by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/1995869/overview">Carlo De Matteis</ext-link>, University of Bari Aldo Moro, Italy</p>
<p><ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/3158064/overview">Runzhe Xu</ext-link>, University of Texas Southwestern Medical Center, United States</p>
</fn>
<corresp id="c001">&#x002A;Correspondence: Dan Chen, <email>wk222222@126.com</email>; Weibin Zhang, <email>zhangwb-0001@163.com</email>; Song Tang, <email>tangsong0802@163.com</email></corresp>
<fn fn-type="equal" id="fn0003"><p><sup>&#x2020;</sup>These authors have contributed equally to this work</p></fn>
</author-notes>
<pub-date pub-type="epub">
<day>23</day>
<month>10</month>
<year>2025</year>
</pub-date>
<pub-date pub-type="collection">
<year>2025</year>
</pub-date>
<volume>12</volume>
<elocation-id>1658150</elocation-id>
<history>
<date date-type="received">
<day>03</day>
<month>07</month>
<year>2025</year>
</date>
<date date-type="accepted">
<day>08</day>
<month>10</month>
<year>2025</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x00A9; 2025 Tang, Luo, Fang, Chen, Liao, Cai, Zhang and Chen.</copyright-statement>
<copyright-year>2025</copyright-year>
<copyright-holder>Tang, Luo, Fang, Chen, Liao, Cai, Zhang and Chen</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p>
</license>
</permissions>
<abstract>
<sec>
<title>Background</title>
<p>The recovery of gastrointestinal function after rectal cancer surgery is a key factor influencing patients&#x2019; postoperative quality of life. This study is the first to explore the role of vitamin B1 and B12 in the recovery of gastrointestinal function after rectal cancer surgery.</p>
</sec>
<sec>
<title>Methods</title>
<p>Eligible patients were divided into four groups: no vitamin group, vitamin B1 alone group, vitamin B12 alone group, and combined vitamin B1 and B12 group. Univariate analysis was used to compare the differences in the time to first flatus among the four groups. Due to the small number of patients using only vitamin B1 or only vitamin B12, these patients were excluded, and univariate and multivariate linear regression analyses were performed on the time to first flatus.</p>
</sec>
<sec>
<title>Results</title>
<p>The time to first flatus exhibited a non-normal distribution. The Kruskal-Wallis rank sum test indicated significant differences in the time to first flatus among the four groups (<italic>p</italic>&#x202F;=&#x202F;0.0152). However, Dunn&#x2019;s pairwise comparison test showed that only the combined vitamin B1 and B12 group differed significantly from the no vitamin group (<italic>p</italic>&#x202F;=&#x202F;0.001). Univariate linear regression analysis demonstrated that intraoperative blood loss (<italic>p</italic>&#x202F;=&#x202F;0.001), enterostomy (<italic>p</italic>&#x202F;=&#x202F;0.002), ileostomy (<italic>p</italic>&#x202F;&#x003C;&#x202F;0.001), and combined use of vitamin B1 and B12 (<italic>p</italic>&#x202F;=&#x202F;0.007) significantly affected the time to first flatus. After removing variable with severe multicollinearity, the results of the multivariate regression analysis showed that intraoperative blood loss (<italic>p</italic> =&#x202F;0.001), ileostomy (<italic>p</italic> =&#x202F;0.001), and combined use of vitamin B1 and B12 (<italic>p</italic> =&#x202F;0.026) still had significant effects on the time to first flatus.</p>
</sec>
<sec>
<title>Conclusion</title>
<p>The combined use of vitamin B1 and B12 can accelerate the recovery of gastrointestinal function after rectal cancer surgery.</p>
</sec>
</abstract>
<kwd-group>
<kwd>vitamin B1</kwd>
<kwd>vitamin B12</kwd>
<kwd>gastrointestinal function</kwd>
<kwd>postoperative recovery</kwd>
<kwd>rectal cancer</kwd>
</kwd-group>
<counts>
<fig-count count="2"/>
<table-count count="1"/>
<equation-count count="0"/>
<ref-count count="33"/>
<page-count count="7"/>
<word-count count="4933"/>
</counts>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Clinical Nutrition</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec sec-type="intro" id="sec1">
<title>Introduction</title>
<p>Colorectal cancer is the third most common cancer and the third leading cause of cancer-related mortality, with rectal cancer accounting for approximately one-third of cases (<xref ref-type="bibr" rid="ref1">1</xref>). Despite significant advances in neoadjuvant therapy in recent years, surgery remains the only curative treatment for rectal cancer (<xref ref-type="bibr" rid="ref2">2</xref>). The postoperative recovery of gastrointestinal function is a key factor influencing the quality of postoperative rehabilitation. If gastrointestinal function recovers quickly, patients can resume oral intake early, replenish nutrients, and enhance their confidence and physical strength. However, delayed gastrointestinal function recovery may lead to nausea, vomiting, abdominal distension, or even bowel obstruction, exacerbating patient suffering, increasing the burden, and potentially prolonging hospital stays.</p>
<p>Previous studies have shown that the use of dexmedetomidine during anesthesia, chewing gum postoperatively, administration of probiotics during the perioperative period, and non-steroidal anti-inflammatory drugs can accelerate the recovery of gastrointestinal function after abdominal surgery (<xref ref-type="bibr" rid="ref3">3</xref>&#x2013;<xref ref-type="bibr" rid="ref9">9</xref>). However, the existing methods and their effects remain limited, with various constraints that cannot fully meet the clinical needs of gastrointestinal surgery. Previous studies have shown that nutrition and metabolism play important roles in colorectal cancer (<xref ref-type="bibr" rid="ref10">10</xref>, <xref ref-type="bibr" rid="ref11">11</xref>). Vitamin B1 and B12, as part of the B-vitamin family, have not been explicitly reported in the literature regarding their role in postoperative gastrointestinal function recovery. Nevertheless, based on long-term empirical observations in our department, vitamin B1 and B12 may have potential benefits in promoting gastrointestinal function recovery.</p>
<p>To further explore the role of vitamin B1 and B12 in gastrointestinal function recovery, we selected rectal cancer as a complex disease model. Rectal cancer surgery involves key surgical factors such as enterostomy and sphincter preservation, which can reflect the practical application value of vitamin B1 and B12 in gastrointestinal function recovery. Through univariate and multivariate analyses of patient data, we comprehensively verified for the first time the effect of vitamin B1 and B12 on postoperative gastrointestinal function recovery. With this study, we aim to provide new therapeutic insights for optimizing postoperative gastrointestinal function recovery, particularly in utilizing simple and low-cost treatments such as vitamin B1 and B12, thereby promoting their clinical application.</p>
</sec>
<sec sec-type="methods" id="sec2">
<title>Methods</title>
<sec id="sec3">
<title>Patient data selection</title>
<p>This study is a retrospective cohort study, selecting data from rectal cancer patients treated at the Second Department of General Surgery (Gastrointestinal Surgery) in our hospital between 2015 and 2024. Inclusion criteria were: (1) rectal cancer patients who underwent surgical treatment; (2) complete medical records with detailed documentation of the first postoperative flatus time. Exclusion criteria were: (1) rectal cancer patients receiving conservative treatment; (2) incomplete medical records with unavailable accurate postoperative first flatus time.</p>
</sec>
<sec id="sec4">
<title>Outcome measure</title>
<p>The first postoperative flatus time is an intuitive and easily observed indicator that effectively reflects gastrointestinal function recovery, previously used as a primary outcome measure in several studies (<xref ref-type="bibr" rid="ref6">6</xref>). Although postoperative defecation time is also commonly used as an indicator of gastrointestinal function recovery, it may not accurately represent gastrointestinal recovery in rectal cancer patients, especially those with bowel obstruction or stomas. The incidence of postoperative bowel obstruction with clear radiological evidence is low in our department, making it an unreliable statistical indicator. Bowel sounds have been previously reported as an unreliable outcome measure for bowel recovery (<xref ref-type="bibr" rid="ref12">12</xref>). Furthermore, postoperative hospital stay is influenced by various factors, including non-gastrointestinal complications. Therefore, to more precisely assess the effects of vitamin B1 and B12 on gastrointestinal recovery, this study uses the first postoperative flatus time as the sole outcome measure. The first flatus time in this study includes flatus through the anus, ileostomy, or colostomy. For convenience, flatus time is rounded to the nearest whole number in days.</p>
</sec>
<sec id="sec5">
<title>Use of vitamin B1 and vitamin B12</title>
<p>None of the patients received vitamin B1 or vitamin B12 supplementation before surgery. Postoperative patients began using vitamin B1 and vitamin B12 upon returning to the ward. The specific regimen was: (1) Vitamin B1 injection, 0.1&#x202F;g, intramuscular injection, once daily; (2) Vitamin B12 injection, 500&#x202F;&#x03BC;g, intramuscular injection, once daily. Other treatments followed standardized postoperative protocols. According to the use of vitamin B1 and B12, patients were divided into four groups: no vitamin group, vitamin B1 alone group, vitamin B12 alone group, and combined vitamin B1 and B12 group.</p>
</sec>
<sec id="sec6">
<title>Patient information</title>
<p>To comprehensively investigate the effects of vitamin B1 and B12 on postoperative gastrointestinal recovery in rectal cancer patients, baseline and perioperative data were collected. Baseline data included gender, age, body mass index (BMI), American Society of Anesthesiologists (ASA) classification, smoking status, alcohol consumption, and comorbidities such as hypertension, coronary heart disease (CHD), or diabetes. Perioperative data included preoperative, intraoperative, and postoperative information. Preoperative data comprised the distance of the tumor from the anal verge, hemoglobin level, albumin level, presence of bowel obstruction, neoadjuvant therapy (chemotherapy, targeted therapy, immunotherapy, and radiotherapy), and neoadjuvant radiotherapy status. Intraoperative data included the type of surgery, combination with other gastrointestinal surgeries, operation duration, blood loss, presence of stoma, and stoma type. Postoperative data included TNM staging, first postoperative flatus time, and the use of vitamin B1 and B12.</p>
</sec>
<sec id="sec7">
<title>Data analysis</title>
<p>All data analyses were performed using R Studio software (R version 4.3.1). First, univariate analysis was conducted to compare the differences in first postoperative flatus time among the four groups. Subsequently, univariate and multivariate linear regression analyses were used to evaluate the effect of combined use of vitamin B1 and B12 on first postoperative flatus time. During the analysis, we also compared the clinic opathological characteristics between the combined vitamin group and the no vitamin group, and performed multicollinearity checks for the variables included in the multivariate linear regression.</p>
</sec>
</sec>
<sec sec-type="results" id="sec8">
<title>Results</title>
<sec id="sec9">
<title>Comparison among the four groups</title>
<p>A total of 167 patients were included in the study. Among them, 123 patients were in the no-vitamin group, 13 patients in the vitamin B1-only group, 7 patients in the vitamin B12-only group, and 24 patients in the combined vitamin B1 and B12 group. Only 5 patients had postoperative bowel obstruction confirmed by imaging evidence, including 4 patients in the no-vitamin group and 1 patient in the vitamin B12-only group.</p>
<p>As the time to first postoperative flatus was non-normally distributed, we first performed the Kruskal-Wallis rank sum test and Dunn&#x2019;s test to compare the differences in time to first postoperative flatus among the four groups. As shown in <xref ref-type="fig" rid="fig1">Figure 1</xref>, the Kruskal-Wallis rank sum test yielded a <italic>p</italic>-value of 0.0152, indicating a statistically significant difference among the four groups. Subsequently, Dunn&#x2019;s pairwise comparison test (<xref ref-type="fig" rid="fig1">Figure 1</xref>) revealed a significant difference between the combined vitamin B1 and B12 group and the no-vitamin group (<italic>p</italic>&#x202F;=&#x202F;0.001).</p>
<fig position="float" id="fig1">
<label>Figure 1</label>
<caption>
<p>Kruskal-Wallis rank sum test and Dunn&#x2019;s test results for time to first postoperative flatus among the four groups.</p>
</caption>
<graphic xlink:href="fnut-12-1658150-g001.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Violin plot comparing first postoperative exsufflation time across four groups: No (n=123), B1 (n=13), B12 (n=7), and B1B12 (n=24). P-values indicate statistical differences, with Kruskal-Wallis p = 0.0152.</alt-text>
</graphic>
</fig>
</sec>
<sec id="sec10">
<title>Univariate linear regression</title>
<p>After excluding patients from the vitamin B1 alone group and the vitamin B12 alone group, 147 patients remained. The distribution of clinicopathological characteristics between the two groups is shown in <xref rid="SM1" ref-type="supplementary-material">Supplementary Table 1</xref>, with significant differences observed only in ASA classification, intraoperative blood loss and hypertension (<italic>p</italic> &#x003C;&#x202F;0.05). Postoperative time to first flatus was used as the dependent variable, while baseline and perioperative data were used as independent variables for univariate linear regression analysis. The results showed that intraoperative blood loss, presence of stoma, stoma type (ileostomy), and combined use of vitamin B1 and vitamin B12 significantly affected postoperative time to first flatus. No other variables showed statistical significance. The results are shown in <xref ref-type="table" rid="tab1">Table 1</xref>.</p>
<table-wrap position="float" id="tab1">
<label>Table 1</label>
<caption>
<p>Results of univariate and multivariate linear regression analysis of the first postoperative flatus time.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top" rowspan="2">Variable</th>
<th align="center" valign="top" colspan="2">Univariate linear regression <italic>&#x03B2;</italic></th>
<th align="center" valign="top" colspan="2">Multiple linear regression <italic>&#x03B2;</italic></th>
</tr>
<tr>
<th align="center" valign="top">(95%CI)</th>
<th align="center" valign="top"><italic>p</italic> value</th>
<th align="center" valign="top">(95%CI)</th>
<th align="center" valign="top"><italic>p</italic> value</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top" colspan="5">Baseline data</td>
</tr>
<tr>
<td align="left" valign="top">Sex (male vs. female)</td>
<td align="center" valign="top">&#x2212;0.129 (&#x2212;0.537, 0.278)</td>
<td align="center" valign="top">0.534</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">Age (year)</td>
<td align="center" valign="top">0.003 (&#x2212;0.014, 0.020)</td>
<td align="center" valign="top">0.728</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">BMI (kg/m<sup>2</sup>)</td>
<td align="center" valign="top">0.030 (&#x2212;0.029, 0.089)</td>
<td align="center" valign="top">0.316</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">ASA (II vs. I)</td>
<td align="center" valign="top">0.223 (&#x2212;0.337, 0.782)</td>
<td align="center" valign="top">0.441</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">ASA (III vs. I)</td>
<td align="center" valign="top">&#x2212;0.413 (&#x2212;1.004, 0.178)</td>
<td align="center" valign="top">0.173</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">Smoke (yes vs. no)</td>
<td align="center" valign="top">0.116 (&#x2212;0.319, 0.551)</td>
<td align="center" valign="top">0.598</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">Alcohol (yes vs. no)</td>
<td align="center" valign="top">0.305 (&#x2212;0.233, 0.843)</td>
<td align="center" valign="top">0.271</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">Hypertension (yes vs. no)</td>
<td align="center" valign="top">0.150 (&#x2212;0.248, 0.548)</td>
<td align="center" valign="top">0.461</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">CHD (yes vs. no)</td>
<td align="center" valign="top">&#x2212;0.395 (&#x2212;0.983, 0.193)</td>
<td align="center" valign="top">0.189</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">Diabetes (yes vs. no)</td>
<td align="center" valign="top">0.248 (&#x2212;0.244, 0.740)</td>
<td align="center" valign="top">0.324</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top" colspan="5">Perioperative data</td>
</tr>
<tr>
<td align="left" valign="top">Tumor distance (cm)</td>
<td align="center" valign="top">0.042 (&#x2212;0.006, 0.090)</td>
<td align="center" valign="top">0.094</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">Hemoglobin (g/L)</td>
<td align="center" valign="top">&#x2212;0.002 (&#x2212;0.012, 0.007)</td>
<td align="center" valign="top">0.660</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">Albumin (g/L)</td>
<td align="center" valign="top">&#x2212;0.009 (&#x2212;0.056, 0.038)</td>
<td align="center" valign="top">0.712</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">Ileus (yes vs. no)</td>
<td align="center" valign="top">&#x2212;0.764 (&#x2212;1.669, 0.140)</td>
<td align="center" valign="top">0.098</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">Neoadjuvant therapy (yes vs. no)</td>
<td align="center" valign="top">&#x2212;0.094 (&#x2212;0.553, 0.365)</td>
<td align="center" valign="top">0.688</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">Neoadjuvant radiotherapy (yes vs. no)</td>
<td align="center" valign="top">0.037 (&#x2212;0.503, 0.577)</td>
<td align="center" valign="top">0.893</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">Operation type (miles vs. dixon)</td>
<td align="center" valign="top">&#x2212;0.015 (&#x2212;0.683, 0.654)</td>
<td align="center" valign="top">0.964</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">Combined surgery (yes vs. no)</td>
<td align="center" valign="top">&#x2212;0.188 (&#x2212;1.174, 0.797)</td>
<td align="center" valign="top">0.707</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">Time (min)</td>
<td align="center" valign="top">0.001 (&#x2212;0.002, 0.003)</td>
<td align="center" valign="top">0.185</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">Blood loss (mL)</td>
<td align="center" valign="top">0.002 (0.001, 0.004)</td>
<td align="center" valign="top"><bold>0.001</bold></td>
<td align="center" valign="top">0.002 (0.001, 0.003)</td>
<td align="center" valign="top"><bold>0.001</bold></td>
</tr>
<tr>
<td align="left" valign="top">Enterostomy (yes vs. no)</td>
<td align="center" valign="top">&#x2212;0.652 (&#x2212;1.069, &#x2212;0.235)</td>
<td align="center" valign="top"><bold>0.002</bold></td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">Enterostomy type (ileum vs. no)</td>
<td align="center" valign="top">&#x2212;0.879 (&#x2212;1.360, &#x2212;0.397)</td>
<td align="center" valign="top"><bold>&#x003C;0.001</bold></td>
<td align="center" valign="top">&#x2212;0.776 (&#x2212;1.238, &#x2212;0.314)</td>
<td align="center" valign="top"><bold>0.001</bold></td>
</tr>
<tr>
<td align="left" valign="top">Enterostomy_type (colon vs. no)</td>
<td align="center" valign="top">&#x2212;0.200 (&#x2212;0.843, 0.443)</td>
<td align="center" valign="top">0.542</td>
<td align="center" valign="top">&#x2212;0.264 (&#x2212;0.876, 0.349)</td>
<td align="center" valign="top">0.401</td>
</tr>
<tr>
<td align="left" valign="top">TNM (II vs. I)</td>
<td align="center" valign="top">0.200 (&#x2212;0.351, 0.751)</td>
<td align="center" valign="top">0.478</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">TNM (III vs. I)</td>
<td align="center" valign="top">0.357 (&#x2212;0.184, 0.900)</td>
<td align="center" valign="top">0.198</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">TNM (IV vs. I)</td>
<td align="center" valign="top">0.200 (&#x2212;0.480, 0.880)</td>
<td align="center" valign="top">0.564</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">Combining vitamins (yes vs. no)</td>
<td align="center" valign="top">&#x2212;0.713 (&#x2212;1.224, &#x2212;0.202)</td>
<td align="center" valign="top"><bold>0.007</bold></td>
<td align="center" valign="top">&#x2212;0.559 (&#x2212;1.046, &#x2212;0.072)</td>
<td align="center" valign="top"><bold>0.026</bold></td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p><italic>&#x03B2;</italic> is the regression coefficient. BMI, body mass index; ASA, American society of anesthesiologists; CHD, coronary heart disease, Tumor distance, Distance between tumor and anal verge. Miles is an abdominoperineal radical resection of rectal cancer, and Dixon is a transabdominal resection of rectal cancer. Bold p-values indicate statistical significance (<italic>p</italic> &#x003C; 0.05).</p>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="sec11">
<title>Multivariate linear regression</title>
<p>We continued to use time to first postoperative flatus as the dependent variable. Due to severe multicollinearity between enterostomy and enterostomy type, only enterostomy type was retained. Multivariate linear regression was then performed using intraoperative blood loss [Variance Inflation Factor (VIF)&#x202F;=&#x202F;1.0017], enterostomy type (VIF&#x202F;=&#x202F;1.0077), and combined use of vitamin B1 and B12 (VIF&#x202F;=&#x202F;1.0157) as independent variables. The results (<xref ref-type="fig" rid="fig2">Figure 2</xref>) showed that intraoperative blood loss, ileostomy, and combined use of vitamin B1 and B12 remained significantly associated with time to first postoperative flatus (<italic>p</italic> &#x003C;&#x202F;0.05), while colostomy had no statistically significant effect (<xref ref-type="table" rid="tab1">Table 1</xref>).</p>
<fig position="float" id="fig2">
<label>Figure 2</label>
<caption>
<p>Results of multivariate linear regression for first postoperative flatus time.</p>
</caption>
<graphic xlink:href="fnut-12-1658150-g002.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Forest plot showing estimates and confidence intervals for three variables: blood loss, enterostomy type, and group. Blood loss has an estimate of 0.002 with p-value 0.001. Enterostomy type includes Ileum with estimate -0.776 and p-value 0.001, and Colon with estimate -0.264 and p-value 0.401. The group variable includes B1B12 with estimate -0.559 and p-value 0.026. Reference categories are marked for some variables.</alt-text>
</graphic>
</fig>
</sec>
</sec>
<sec sec-type="discussion" id="sec12">
<title>Discussion</title>
<p>Rectal cancer accounts for about one-third of colorectal cancers, making it the eighth most common cancer worldwide and the tenth leading cause of cancer-related deaths (<xref ref-type="bibr" rid="ref1">1</xref>, <xref ref-type="bibr" rid="ref13">13</xref>). Surgery remains the only curative treatment for rectal cancer. Total mesorectal excision has become the gold standard for rectal cancer surgery (<xref ref-type="bibr" rid="ref14">14</xref>). For patients with low rectal cancer, two surgical approaches are available: one is abdominal rectal cancer resection with sphincter preservation, also known as anterior resection, and the other is abdominoperineal resection, which often requires the establishment of a permanent colostomy (<xref ref-type="bibr" rid="ref15">15</xref>). However, regardless of the chosen surgical method, the recovery of gastrointestinal function is critical to the overall postoperative recovery of patients, especially in the era advocating for enhanced recovery after surgery.</p>
<p>Postoperative gum chewing has been widely proven to accelerate the recovery of gastrointestinal function in abdominal and orthopedic surgeries (<xref ref-type="bibr" rid="ref3">3</xref>&#x2013;<xref ref-type="bibr" rid="ref5">5</xref>, <xref ref-type="bibr" rid="ref16">16</xref>, <xref ref-type="bibr" rid="ref17">17</xref>). However, the specific mechanism is not yet fully clear. Previous studies suggest that chewing gum stimulates the head-vagus nerve, promotes the secretion of gastrointestinal hormones, and thus stimulates gastrointestinal motility, as well as promotes the secretion of pancreatic juice and saliva, creating a &#x201C;sham feeding&#x201D; effect (<xref ref-type="bibr" rid="ref18">18</xref>). Furthermore, certain types of gum, particularly sugar-free gum, contain ingredients like sorbitol, which may have a laxative effect (<xref ref-type="bibr" rid="ref18">18</xref>). However, in previous studies, certain exclusion criteria have been set for postoperative gum chewing, such as excluding individuals with a history of abdominal surgery, children, patients with intraoperative or postoperative complications, and common comorbidities such as diabetes (<xref ref-type="bibr" rid="ref17">17</xref>). This has limited the widespread applicability of this method.</p>
<p>Dexmedetomidine, an intraoperative anesthetic sedative, has been shown to accelerate the recovery of gastrointestinal function (<xref ref-type="bibr" rid="ref8">8</xref>, <xref ref-type="bibr" rid="ref9">9</xref>). However, meta-analyses point out that the evidence is weak and there is a lack of clear dosage recommendations (<xref ref-type="bibr" rid="ref9">9</xref>). Nonsteroidal anti-inflammatory drugs (NSAIDs) have also been shown to promote gastrointestinal recovery, but existing evidence is insufficient to determine whether selective or non-selective drugs are preferable (<xref ref-type="bibr" rid="ref7">7</xref>). Additionally, NSAIDs may increase gastric mucosal injury (<xref ref-type="bibr" rid="ref19">19</xref>). For complex surgeries like rectal cancer, this undoubtedly increases the risk of stress-related gastric ulcers. Some studies have shown that <italic>Bacillus subtilis</italic> TBC169 probiotics can accelerate postoperative gastrointestinal recovery in gynecological laparoscopic surgery patients (<xref ref-type="bibr" rid="ref6">6</xref>). However, there are multiple limitations in these studies, such as excluding patients with a history of intestinal surgery and those with long operative times.</p>
<p>Given the limitations of current methods and their limited effectiveness, existing treatments do not fully meet the needs of gastrointestinal surgery clinical practice. Therefore, more simple, cost-effective, and widely applicable options need to be explored. In long-term clinical practice, we observed that vitamins B1 and B12 may have potential benefits in promoting gastrointestinal recovery. Based on this, we conducted a retrospective cohort analysis focusing on the complex condition of rectal cancer surgery.</p>
<p>We first performed univariate analysis on the four groups. The results showed that the <italic>p</italic>-value from the Kruskal-Wallis test was 0.0152, suggesting significant differences in the first postoperative flatus time among the four groups. However, paired comparisons from the Dunn test indicated that only the group receiving both vitamin B1 and B12 showed a significant difference compared to the no-vitamin group (<italic>p</italic>&#x202F;=&#x202F;0.001). This may indicate that vitamin B1 and B12 have a synergistic effect, which is not significant when used alone.</p>
<p>After excluding patients who received only vitamin B1 or only vitamin B12, and considering that gastrointestinal recovery may be influenced by patients&#x2019; physical conditions and perioperative procedures, we performed univariate and multivariate linear regression analysis on the first postoperative flatus time. Linear regression was chosen because all patients experienced the event before discharge, the outcome was measured in days, and the data had moderate dispersion, allowing for straightforward interpretation of covariate effects on mean flatus time. Univariate linear regression results showed that intraoperative blood loss, enterostomy, ileostomy, and combined use of vitamins B1 and B12 significantly influenced the time to first postoperative flatus. After removing variables with severe multicollinearity, the results of the multivariate linear regression analysis showed that intraoperative blood loss, ileostomy, and combined use of vitamin B1 and B12 still had significant effects on the time to first flatus. Specifically, increased intraoperative blood loss prolonged the time to first flatus, whereas ileostomy and the combined use of vitamin B1 and B12 significantly shortened it.</p>
<p>The impact of intraoperative blood loss on first flatus time has been reported in previous studies. Extensive blood loss can exacerbate the sympathetic and endocrine stress responses, leading to more intestinal injury and inflammation, thus delaying gastrointestinal recovery (<xref ref-type="bibr" rid="ref20">20</xref>). Although ileostomy and colostomy did not show significant differences in multivariate regression analysis, they still have some plausibility from a practical standpoint. Generally, small bowel peristalsis recovers the fastest after surgery (within 24&#x202F;h), followed by the stomach (24&#x2013;48&#x202F;h), and then the large intestine (48&#x2013;72&#x202F;h) (<xref ref-type="bibr" rid="ref21">21</xref>, <xref ref-type="bibr" rid="ref22">22</xref>). Therefore, a stoma, especially an ileostomy, can shorten the distance from the small intestine to the stoma, which may explain why a significant difference was observed for ileostomy in the analysis.</p>
<p>The mechanism by which combined use of vitamins B1 and B12 promotes gastrointestinal recovery is currently unclear. Both vitamins are B vitamins. Studies have shown that B vitamins are associated with gut microbiota (<xref ref-type="bibr" rid="ref23">23</xref>). Vitamin B12, also known as cobalamin, is synthesized and utilized by bacteria in the human gut microbiome and may be related to changes in gut bacterial abundance and diversity (<xref ref-type="bibr" rid="ref24">24</xref>&#x2013;<xref ref-type="bibr" rid="ref26">26</xref>). Vitamin B12 injection is commonly used to treat B12 deficiency in patients with malabsorption (<xref ref-type="bibr" rid="ref24">24</xref>). Additionally, supplementing vitamin B12 may benefit gastrointestinal diseases through its interaction with the gut microbiota (<xref ref-type="bibr" rid="ref24">24</xref>). Vitamin B1, also known as thiamine, cannot be synthesized endogenously in humans, and its supply is entirely dependent on dietary intake (<xref ref-type="bibr" rid="ref27">27</xref>). Thiamine deficiency can occur in gastrointestinal surgery, malnutrition, refeeding syndrome, and alcoholism (<xref ref-type="bibr" rid="ref28">28</xref>). Thiamine deficiency inhibits pancreatic acinar cells, significantly reducing digestive enzyme secretion (<xref ref-type="bibr" rid="ref29">29</xref>). Some studies also suggest that thiamine can alleviate symptoms of abdominal pain, nausea, vomiting, and anorexia (<xref ref-type="bibr" rid="ref30">30</xref>, <xref ref-type="bibr" rid="ref31">31</xref>). In terms of safety, both vitamins B1 and B12 are water-soluble vitamins with short half-lives and are rapidly excreted from the body (<xref ref-type="bibr" rid="ref32">32</xref>, <xref ref-type="bibr" rid="ref33">33</xref>).</p>
<p>Although our study is the first to demonstrate that combined use vitamin B1 and B12 can accelerate postoperative gastrointestinal recovery in patients with rectal cancer, several limitations should be acknowledged. First, the number of patients receiving vitamin B1 or B12 alone was small, and these groups were excluded from the primary analysis, which may introduce potential bias. Therefore, larger studies are needed to clarify the independent effects of vitamin B1 and B12. Second, the precise mechanisms by which the combination of vitamin B1 and B12 promotes gastrointestinal recovery remain unclear and warrant further basic and clinical investigation. Third, as this was a retrospective study, the recording of time to first postoperative flatus was not standardized; for convenience, the values were rounded, which may reduce precision and introduce some error. Finally, although no patients received vitamin B1 or B12 preoperatively, their baseline levels were not routinely measured in prior clinical care, highlighting the need for future prospective studies to assess this factor more comprehensively.</p>
</sec>
<sec sec-type="conclusions" id="sec13">
<title>Conclusion</title>
<p>The combined use of vitamins B1 and B12 offers a new, simple, cost-effective, and safe treatment option for promoting gastrointestinal recovery after rectal cancer surgery, but further research is needed to establish its broad clinical applicability and elucidate its mechanism of action.</p>
</sec>
</body>
<back>
<sec sec-type="data-availability" id="sec14">
<title>Data availability statement</title>
<p>The original contributions presented in the study are included in the article/<xref rid="SM1" ref-type="supplementary-material">Supplementary material</xref>, further inquiries can be directed to the corresponding authors.</p>
</sec>
<sec sec-type="ethics-statement" id="sec15">
<title>Ethics statement</title>
<p>The studies involving humans were approved by The Ethics Committee of the First Affiliated Hospital of Guangdong Pharmaceutical University. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.</p>
</sec>
<sec sec-type="author-contributions" id="sec16">
<title>Author contributions</title>
<p>ST: Formal analysis, Software, Writing &#x2013; original draft, Methodology, Data curation, Visualization, Investigation, Conceptualization, Funding acquisition. SL: Formal analysis, Writing &#x2013; original draft. WF: Methodology, Data curation, Writing &#x2013; original draft. ZC: Writing &#x2013; original draft, Data curation. YL: Data curation, Writing &#x2013; original draft. HC: Writing &#x2013; original draft, Data curation. WZ: Supervision, Writing &#x2013; review &#x0026; editing, Project administration. DC: Project administration, Supervision, Writing &#x2013; review &#x0026; editing.</p>
</sec>
<sec sec-type="funding-information" id="sec17">
<title>Funding</title>
<p>The author(s) declare that financial support was received for the research and/or publication of this article. This research was supported by the Education and Teaching Research and Reform Project of the First Affiliated Hospital of Guangdong Pharmaceutical University (No. 2024JX10).</p>
</sec>
<sec sec-type="COI-statement" id="sec18">
<title>Conflict of interest</title>
<p>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.</p>
</sec>
<sec sec-type="ai-statement" id="sec19">
<title>Generative AI statement</title>
<p>The authors declare that no Gen AI was used in the creation of this manuscript.</p>
<p>Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.</p>
</sec>
<sec sec-type="disclaimer" id="sec20">
<title>Publisher&#x2019;s note</title>
<p>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.</p>
</sec>
<sec sec-type="supplementary-material" id="sec21">
<title>Supplementary material</title>
<p>The Supplementary material for this article can be found online at: <ext-link xlink:href="https://www.frontiersin.org/articles/10.3389/fnut.2025.1658150/full#supplementary-material" ext-link-type="uri">https://www.frontiersin.org/articles/10.3389/fnut.2025.1658150/full#supplementary-material</ext-link></p>
<supplementary-material xlink:href="Table_1.docx" id="SM1" mimetype="application/vnd.openxmlformats-officedocument.wordprocessingml.document" xmlns:xlink="http://www.w3.org/1999/xlink"/>
</sec>
<ref-list>
<title>References</title>
<ref id="ref1"><label>1.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Siegel</surname><given-names>RL</given-names></name> <name><surname>Miller</surname><given-names>KD</given-names></name> <name><surname>Fuchs</surname><given-names>HE</given-names></name> <name><surname>Jemal</surname><given-names>A</given-names></name></person-group>. <article-title>Cancer statistics, 2022</article-title>. <source>CA Cancer J Clin</source>. (<year>2022</year>) <volume>72</volume>:<fpage>7</fpage>&#x2013;<lpage>33</lpage>. doi: <pub-id pub-id-type="doi">10.3322/caac.21708</pub-id>, PMID: <pub-id pub-id-type="pmid">35020204</pub-id></citation></ref>
<ref id="ref2"><label>2.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Keller</surname><given-names>DS</given-names></name> <name><surname>Berho</surname><given-names>M</given-names></name> <name><surname>Perez</surname><given-names>RO</given-names></name> <name><surname>Wexner</surname><given-names>SD</given-names></name> <name><surname>Chand</surname><given-names>M</given-names></name></person-group>. <article-title>The multidisciplinary management of rectal cancer</article-title>. <source>Nat Rev Gastroenterol Hepatol</source>. (<year>2020</year>) <volume>17</volume>:<fpage>414</fpage>&#x2013;<lpage>29</lpage>. doi: <pub-id pub-id-type="doi">10.1038/s41575-020-0275-y</pub-id>, PMID: <pub-id pub-id-type="pmid">32203400</pub-id></citation></ref>
<ref id="ref3"><label>3.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Liu</surname><given-names>Q</given-names></name> <name><surname>Jiang</surname><given-names>H</given-names></name> <name><surname>Xu</surname><given-names>D</given-names></name> <name><surname>Jin</surname><given-names>J</given-names></name></person-group>. <article-title>Effect of gum chewing on ameliorating ileus following colorectal surgery: a meta-analysis of 18 randomized controlled trials</article-title>. <source>Int J Surg (London, England)</source>. (<year>2017</year>) <volume>47</volume>:<fpage>107</fpage>&#x2013;<lpage>15</lpage>. doi: <pub-id pub-id-type="doi">10.1016/j.ijsu.2017.07.107</pub-id>, PMID: <pub-id pub-id-type="pmid">28867465</pub-id></citation></ref>
<ref id="ref4"><label>4.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Mei</surname><given-names>B</given-names></name> <name><surname>Wang</surname><given-names>W</given-names></name> <name><surname>Cui</surname><given-names>F</given-names></name> <name><surname>Wen</surname><given-names>Z</given-names></name> <name><surname>Shen</surname><given-names>M</given-names></name></person-group>. <article-title>Chewing gum for intestinal function recovery after colorectal cancer surgery: a systematic review and meta-analysis</article-title>. <source>Gastro Res Pract</source>. (<year>2017</year>) <volume>2017</volume>:<fpage>3087904</fpage>. doi: <pub-id pub-id-type="doi">10.1155/2017/3087904</pub-id></citation></ref>
<ref id="ref5"><label>5.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Pereira Gomes Morais</surname><given-names>E</given-names></name> <name><surname>Riera</surname><given-names>R</given-names></name> <name><surname>Porf&#x00ED;rio</surname><given-names>GJ</given-names></name> <name><surname>Macedo</surname><given-names>CR</given-names></name> <name><surname>Sarmento Vasconcelos</surname><given-names>V</given-names></name> <name><surname>de Souza Pedrosa</surname><given-names>A</given-names></name> <etal/></person-group>. <article-title>Chewing gum for enhancing early recovery of bowel function after caesarean section</article-title>. <source>Cochrane Database Syst Rev</source>. (<year>2016</year>) <volume>10</volume>:<fpage>Cd011562</fpage>. doi: <pub-id pub-id-type="doi">10.1002/14651858.CD011562.pub2</pub-id></citation></ref>
<ref id="ref6"><label>6.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Li</surname><given-names>Z</given-names></name> <name><surname>Guan</surname><given-names>Z</given-names></name> <name><surname>Bai</surname><given-names>N</given-names></name> <name><surname>Yan</surname><given-names>Y</given-names></name> <name><surname>Niu</surname><given-names>Z</given-names></name> <name><surname>Xu</surname><given-names>J</given-names></name> <etal/></person-group>. <article-title><italic>Bacillus coagulans</italic> TBC169 probiotics for the recovery of intestinal function after gynecological laparoscopic surgery: a randomized, placebo-controlled trial</article-title>. <source>Int J Clin Pharm</source>. (<year>2022</year>) <volume>44</volume>:<fpage>1287</fpage>&#x2013;<lpage>95</lpage>. doi: <pub-id pub-id-type="doi">10.1007/s11096-022-01451-2</pub-id>, PMID: <pub-id pub-id-type="pmid">35882823</pub-id></citation></ref>
<ref id="ref7"><label>7.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Milne</surname><given-names>TGE</given-names></name> <name><surname>Jaung</surname><given-names>R</given-names></name> <name><surname>O'Grady</surname><given-names>G</given-names></name> <name><surname>Bissett</surname><given-names>IP</given-names></name></person-group>. <article-title>Nonsteroidal anti-inflammatory drugs reduce the time to recovery of gut function after elective colorectal surgery: a systematic review and meta-analysis</article-title>. <source>Colorectal Dis</source>. (<year>2018</year>) <volume>20</volume>:<fpage>O190</fpage>&#x2013;<lpage>8</lpage>. doi: <pub-id pub-id-type="doi">10.1111/codi.14268</pub-id>, PMID: <pub-id pub-id-type="pmid">29781564</pub-id></citation></ref>
<ref id="ref8"><label>8.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Wu</surname><given-names>Y</given-names></name> <name><surname>Cai</surname><given-names>Z</given-names></name> <name><surname>Liu</surname><given-names>L</given-names></name> <name><surname>Wang</surname><given-names>J</given-names></name> <name><surname>Li</surname><given-names>Y</given-names></name> <name><surname>Kang</surname><given-names>Y</given-names></name> <etal/></person-group>. <article-title>Impact of intravenous dexmedetomidine on gastrointestinal function recovery after laparoscopic hysteromyomectomy: a randomized clinical trial</article-title>. <source>Sci Rep</source>. (<year>2022</year>) <volume>12</volume>:<fpage>14640</fpage>. doi: <pub-id pub-id-type="doi">10.1038/s41598-022-18729-0</pub-id>, PMID: <pub-id pub-id-type="pmid">36030343</pub-id></citation></ref>
<ref id="ref9"><label>9.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Behera</surname><given-names>BK</given-names></name> <name><surname>Misra</surname><given-names>S</given-names></name> <name><surname>Jena</surname><given-names>SS</given-names></name> <name><surname>Mohanty</surname><given-names>CR</given-names></name></person-group>. <article-title>The effect of perioperative dexmedetomidine on postoperative bowel function recovery in adult patients receiving general anesthesia</article-title>. <source>Minerva Anestesiol</source>. (<year>2022</year>) <volume>88</volume>:<fpage>51</fpage>&#x2013;<lpage>61</lpage>. doi: <pub-id pub-id-type="doi">10.23736/S0375-9393.21.15773-6</pub-id></citation></ref>
<ref id="ref10"><label>10.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Crudele</surname><given-names>L</given-names></name> <name><surname>De Matteis</surname><given-names>C</given-names></name> <name><surname>Novielli</surname><given-names>F</given-names></name> <name><surname>Petruzzelli</surname><given-names>S</given-names></name> <name><surname>Di Buduo</surname><given-names>E</given-names></name> <name><surname>Graziano</surname><given-names>G</given-names></name> <etal/></person-group>. <article-title>Fasting hyperglycaemia and fatty liver drive colorectal cancer: a retrospective analysis in 1145 patients</article-title>. <source>Intern Emerg Med</source>. (<year>2024</year>) <volume>19</volume>:<fpage>1267</fpage>&#x2013;<lpage>77</lpage>. doi: <pub-id pub-id-type="doi">10.1007/s11739-024-03596-6</pub-id>, PMID: <pub-id pub-id-type="pmid">38668822</pub-id></citation></ref>
<ref id="ref11"><label>11.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>De Matteis</surname><given-names>C</given-names></name> <name><surname>Crudele</surname><given-names>L</given-names></name> <name><surname>Gadaleta</surname><given-names>RM</given-names></name> <name><surname>Di Buduo</surname><given-names>E</given-names></name> <name><surname>Novielli</surname><given-names>E</given-names></name> <name><surname>Petruzzelli</surname><given-names>S</given-names></name> <etal/></person-group>. <article-title>Low adherence to Mediterranean diet characterizes metabolic patients with gastrointestinal cancer</article-title>. <source>Nutrients</source>. (<year>2024</year>) <volume>16</volume>:<fpage>630</fpage>. doi: <pub-id pub-id-type="doi">10.3390/nu16050630</pub-id>, PMID: <pub-id pub-id-type="pmid">38474758</pub-id></citation></ref>
<ref id="ref12"><label>12.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Read</surname><given-names>TE</given-names></name> <name><surname>Brozovich</surname><given-names>M</given-names></name> <name><surname>Andujar</surname><given-names>JE</given-names></name> <name><surname>Ricciardi</surname><given-names>R</given-names></name> <name><surname>Caushaj</surname><given-names>PF</given-names></name></person-group>. <article-title>Bowel sounds are not associated with flatus, bowel movement, or tolerance of oral intake in patients after major abdominal surgery</article-title>. <source>Dis Colon Rectum</source>. (<year>2017</year>) <volume>60</volume>:<fpage>608</fpage>&#x2013;<lpage>13</lpage>. doi: <pub-id pub-id-type="doi">10.1097/DCR.0000000000000829</pub-id>, PMID: <pub-id pub-id-type="pmid">28481855</pub-id></citation></ref>
<ref id="ref13"><label>13.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Sung</surname><given-names>H</given-names></name> <name><surname>Ferlay</surname><given-names>J</given-names></name> <name><surname>Siegel</surname><given-names>RL</given-names></name> <name><surname>Laversanne</surname><given-names>M</given-names></name> <name><surname>Soerjomataram</surname><given-names>L</given-names></name> <name><surname>Jemal</surname><given-names>A</given-names></name> <etal/></person-group>. <article-title>Global Cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries</article-title>. <source>CA Cancer J Clin</source>. (<year>2021</year>) <volume>71</volume>:<fpage>209</fpage>&#x2013;<lpage>49</lpage>. doi: <pub-id pub-id-type="doi">10.3322/caac.21660</pub-id></citation></ref>
<ref id="ref14"><label>14.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Enker</surname><given-names>WE</given-names></name></person-group>. <article-title>Total mesorectal excision--the new golden standard of surgery for rectal cancer</article-title>. <source>Ann Med</source>. (<year>1997</year>) <volume>29</volume>:<fpage>127</fpage>&#x2013;<lpage>33</lpage>. doi: <pub-id pub-id-type="doi">10.3109/07853899709113698</pub-id>, PMID: <pub-id pub-id-type="pmid">9187227</pub-id></citation></ref>
<ref id="ref15"><label>15.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Herrinton</surname><given-names>LJ</given-names></name> <name><surname>Altschuler</surname><given-names>A</given-names></name> <name><surname>McMullen</surname><given-names>CK</given-names></name> <name><surname>Bulkley</surname><given-names>JE</given-names></name> <name><surname>Hornbrook</surname><given-names>MC</given-names></name> <name><surname>Sun</surname><given-names>V</given-names></name> <etal/></person-group>. <article-title>Conversations for providers caring for patients with rectal cancer: comparison of long-term patient-centered outcomes for patients with low rectal cancer facing ostomy or sphincter-sparing surgery</article-title>. <source>CA Cancer J Clin</source>. (<year>2016</year>) <volume>66</volume>:<fpage>387</fpage>&#x2013;<lpage>97</lpage>. doi: <pub-id pub-id-type="doi">10.3322/caac.21345</pub-id>, PMID: <pub-id pub-id-type="pmid">26999757</pub-id></citation></ref>
<ref id="ref16"><label>16.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Liao</surname><given-names>XQ</given-names></name> <name><surname>Li</surname><given-names>SL</given-names></name> <name><surname>Peng</surname><given-names>YC</given-names></name> <name><surname>Chen</surname><given-names>LW</given-names></name> <name><surname>Lin</surname><given-names>YJ</given-names></name></person-group>. <article-title>Effects of chewing gum on gastrointestinal function in patients following spinal surgery: a meta-analysis and systematic review</article-title>. <source>Eur Spine J</source>. (<year>2022</year>) <volume>31</volume>:<fpage>2536</fpage>&#x2013;<lpage>46</lpage>. doi: <pub-id pub-id-type="doi">10.1007/s00586-022-07304-w</pub-id>, PMID: <pub-id pub-id-type="pmid">35852608</pub-id></citation></ref>
<ref id="ref17"><label>17.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Short</surname><given-names>V</given-names></name> <name><surname>Herbert</surname><given-names>G</given-names></name> <name><surname>Perry</surname><given-names>R</given-names></name> <name><surname>Atkinson</surname><given-names>C</given-names></name> <name><surname>Ness</surname><given-names>AR</given-names></name> <name><surname>Penfold</surname><given-names>C</given-names></name> <etal/></person-group>. <article-title>Chewing gum for postoperative recovery of gastrointestinal function</article-title>. <source>Cochrane Database Syst Rev</source>. (<year>2015</year>) <volume>2015</volume>:<fpage>Cd006506</fpage>. doi: <pub-id pub-id-type="doi">10.1002/14651858.CD006506.pub3</pub-id>, PMID: <pub-id pub-id-type="pmid">25914904</pub-id></citation></ref>
<ref id="ref18"><label>18.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Tandeter</surname><given-names>H</given-names></name></person-group>. <article-title>Hypothesis: hexitols in chewing gum may play a role in reducing postoperative ileus</article-title>. <source>Med Hypotheses</source>. (<year>2009</year>) <volume>72</volume>:<fpage>39</fpage>&#x2013;<lpage>40</lpage>. doi: <pub-id pub-id-type="doi">10.1016/j.mehy.2008.06.044</pub-id>, PMID: <pub-id pub-id-type="pmid">18783895</pub-id></citation></ref>
<ref id="ref19"><label>19.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Igarashi</surname><given-names>M</given-names></name> <name><surname>Takagi</surname><given-names>A</given-names></name> <name><surname>Jiang</surname><given-names>X</given-names></name> <name><surname>Hasumi</surname><given-names>K</given-names></name> <name><surname>Watanabe</surname><given-names>S</given-names></name> <name><surname>Deguchi</surname><given-names>R</given-names></name> <etal/></person-group>. <article-title>Analysis of <italic>helicobacter pylori</italic> and nonsteroidal anti-inflammatory drug-induced gastric epithelial injury</article-title>. <source>Aliment Pharmacol Ther</source>. (<year>2002</year>) <volume>16</volume>:<fpage>235</fpage>&#x2013;<lpage>9</lpage>. doi: <pub-id pub-id-type="doi">10.1046/j.1365-2036.16.s2.6.x</pub-id></citation></ref>
<ref id="ref20"><label>20.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Artinyan</surname><given-names>A</given-names></name> <name><surname>Nunoo-Mensah</surname><given-names>JW</given-names></name> <name><surname>Balasubramaniam</surname><given-names>S</given-names></name> <name><surname>Gauderman</surname><given-names>J</given-names></name> <name><surname>Essani</surname><given-names>R</given-names></name> <name><surname>Gonzalez-Ruiz</surname><given-names>C</given-names></name> <etal/></person-group>. <article-title>Prolonged postoperative ileus-definition, risk factors, and predictors after surgery</article-title>. <source>World J Surg</source>. (<year>2008</year>) <volume>32</volume>:<fpage>1495</fpage>&#x2013;<lpage>500</lpage>. doi: <pub-id pub-id-type="doi">10.1007/s00268-008-9491-2</pub-id>, PMID: <pub-id pub-id-type="pmid">18305994</pub-id></citation></ref>
<ref id="ref21"><label>21.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Nimarta</surname></name> <name><surname>Singh</surname><given-names>NV</given-names></name> <name><surname>Shruti</surname></name> <name><surname>Gupta</surname><given-names>RJ</given-names></name></person-group>. <article-title>Effectiveness of chewing gum on bowel motility among the patients who have undergone abdominal surgery</article-title>. <source>Int J Midwifery Nurs Pract</source>. (<year>2013</year>) <volume>9</volume>:<fpage>108</fpage>&#x2013;<lpage>17</lpage>. doi: <pub-id pub-id-type="doi">10.33698/NRF0159</pub-id></citation></ref>
<ref id="ref22"><label>22.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Gervaz</surname><given-names>P</given-names></name> <name><surname>Bucher</surname><given-names>P</given-names></name> <name><surname>Scheiwiller</surname><given-names>A</given-names></name> <name><surname>Mugnier-Konrad</surname><given-names>B</given-names></name> <name><surname>Morel</surname><given-names>P</given-names></name></person-group>. <article-title>The duration of postoperative ileus after elective colectomy is correlated to surgical specialization</article-title>. <source>Int J Color Dis</source>. (<year>2006</year>) <volume>21</volume>:<fpage>542</fpage>&#x2013;<lpage>6</lpage>. doi: <pub-id pub-id-type="doi">10.1007/s00384-005-0050-0</pub-id>, PMID: <pub-id pub-id-type="pmid">16267669</pub-id></citation></ref>
<ref id="ref23"><label>23.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Uebanso</surname><given-names>T</given-names></name> <name><surname>Shimohata</surname><given-names>T</given-names></name> <name><surname>Mawatari</surname><given-names>K</given-names></name> <name><surname>Takahashi</surname><given-names>A</given-names></name></person-group>. <article-title>Functional roles of B-vitamins in the gut and gut microbiome</article-title>. <source>Mol Nutr Food Res</source>. (<year>2020</year>) <volume>64</volume>:<fpage>e2000426</fpage>. doi: <pub-id pub-id-type="doi">10.1002/mnfr.202000426</pub-id>, PMID: <pub-id pub-id-type="pmid">32761878</pub-id></citation></ref>
<ref id="ref24"><label>24.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Guetterman</surname><given-names>HM</given-names></name> <name><surname>Huey</surname><given-names>SL</given-names></name> <name><surname>Knight</surname><given-names>R</given-names></name> <name><surname>Fox</surname><given-names>AM</given-names></name> <name><surname>Mehta</surname><given-names>S</given-names></name> <name><surname>Finkelstein</surname><given-names>JL</given-names></name></person-group>. <article-title>Vitamin B-12 and the gastrointestinal microbiome: a systematic review</article-title>. <source>Adv Nut (Bethesda, Md)</source>. (<year>2022</year>) <volume>13</volume>:<fpage>530</fpage>&#x2013;<lpage>58</lpage>. doi: <pub-id pub-id-type="doi">10.1093/advances/nmab123</pub-id>, PMID: <pub-id pub-id-type="pmid">34612492</pub-id></citation></ref>
<ref id="ref25"><label>25.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>H</given-names></name> <name><surname>Shou</surname><given-names>Y</given-names></name> <name><surname>Zhu</surname><given-names>X</given-names></name> <name><surname>Xu</surname><given-names>Y</given-names></name> <name><surname>Shi</surname><given-names>L</given-names></name> <name><surname>Xiang</surname><given-names>S</given-names></name> <etal/></person-group>. <article-title>Stability of vitamin B12 with the protection of whey proteins and their effects on the gut microbiome</article-title>. <source>Food Chem</source>. (<year>2019</year>) <volume>276</volume>:<fpage>298</fpage>&#x2013;<lpage>306</lpage>. doi: <pub-id pub-id-type="doi">10.1016/j.foodchem.2018.10.033</pub-id>, PMID: <pub-id pub-id-type="pmid">30409598</pub-id></citation></ref>
<ref id="ref26"><label>26.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Wienhausen</surname><given-names>G</given-names></name> <name><surname>Moraru</surname><given-names>C</given-names></name> <name><surname>Bruns</surname><given-names>S</given-names></name> <name><surname>Tran</surname><given-names>DQ</given-names></name> <name><surname>Sultana</surname><given-names>S</given-names></name> <name><surname>Wilkes</surname><given-names>H</given-names></name> <etal/></person-group>. <article-title>Ligand cross-feeding resolves bacterial vitamin B(12) auxotrophies</article-title>. <source>Nature</source>. (<year>2024</year>) <volume>629</volume>:<fpage>886</fpage>&#x2013;<lpage>92</lpage>. doi: <pub-id pub-id-type="doi">10.1038/s41586-024-07396-y</pub-id>, PMID: <pub-id pub-id-type="pmid">38720071</pub-id></citation></ref>
<ref id="ref27"><label>27.</label><citation citation-type="book"><person-group person-group-type="author"><name><surname>Lawrence</surname><given-names>RA</given-names></name> <name><surname>Lawrence</surname><given-names>RM</given-names></name></person-group>. <source>Breastfeeding: a guide for the medical professional</source>. <publisher-name>Philadelphia: Elsevier Health Sciences</publisher-name> (<year>2021</year>).</citation></ref>
<ref id="ref28"><label>28.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Polegato</surname><given-names>BF</given-names></name> <name><surname>Pereira</surname><given-names>AG</given-names></name> <name><surname>Azevedo</surname><given-names>PS</given-names></name> <name><surname>Costa</surname><given-names>NA</given-names></name> <name><surname>Zornoff</surname><given-names>LAM</given-names></name> <name><surname>Paiva</surname><given-names>SAR</given-names></name> <etal/></person-group>. <article-title>Role of thiamin in health and disease</article-title>. <source>Nutr Clin Pract</source>. (<year>2019</year>) <volume>34</volume>:<fpage>558</fpage>&#x2013;<lpage>64</lpage>. doi: <pub-id pub-id-type="doi">10.1002/ncp.10234</pub-id>, PMID: <pub-id pub-id-type="pmid">30644592</pub-id></citation></ref>
<ref id="ref29"><label>29.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Singh</surname><given-names>M</given-names></name></person-group>. <article-title>Effect of thiamin deficiency on pancreatic acinar cell function</article-title>. <source>Am J Clin Nutr</source>. (<year>1982</year>) <volume>36</volume>:<fpage>500</fpage>&#x2013;<lpage>4</lpage>. doi: <pub-id pub-id-type="doi">10.1093/ajcn/36.3.500</pub-id>, PMID: <pub-id pub-id-type="pmid">6180623</pub-id></citation></ref>
<ref id="ref30"><label>30.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Donnino</surname><given-names>M</given-names></name></person-group>. <article-title>Gastrointestinal beriberi: a previously unrecognized syndrome</article-title>. <source>Ann Intern Med</source>. (<year>2004</year>) <volume>141</volume>:<fpage>898</fpage>&#x2013;<lpage>9</lpage>. doi: <pub-id pub-id-type="doi">10.7326/0003-4819-141-11-200412070-00035</pub-id>, PMID: <pub-id pub-id-type="pmid">15583247</pub-id></citation></ref>
<ref id="ref31"><label>31.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Smith</surname><given-names>TJ</given-names></name> <name><surname>Johnson</surname><given-names>CR</given-names></name> <name><surname>Koshy</surname><given-names>R</given-names></name> <name><surname>Hess</surname><given-names>SY</given-names></name> <name><surname>Qureshi</surname><given-names>UA</given-names></name> <name><surname>Mynak</surname><given-names>ML</given-names></name> <etal/></person-group>. <article-title>Thiamine deficiency disorders: a clinical perspective</article-title>. <source>Ann N Y Acad Sci</source>. (<year>2021</year>) <volume>1498</volume>:<fpage>9</fpage>&#x2013;<lpage>28</lpage>. doi: <pub-id pub-id-type="doi">10.1111/nyas.14536</pub-id>, PMID: <pub-id pub-id-type="pmid">33305487</pub-id></citation></ref>
<ref id="ref32"><label>32.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Tallaksen</surname><given-names>CM</given-names></name> <name><surname>Sande</surname><given-names>A</given-names></name> <name><surname>B&#x00F8;hmer</surname><given-names>T</given-names></name> <name><surname>Bell</surname><given-names>H</given-names></name> <name><surname>Karlsen</surname><given-names>J</given-names></name></person-group>. <article-title>Kinetics of thiamin and thiamin phosphate esters in human blood, plasma and urine after 50 mg intravenously or orally</article-title>. <source>Eur J Clin Pharmacol</source>. (<year>1993</year>) <volume>44</volume>:<fpage>73</fpage>&#x2013;<lpage>8</lpage>. doi: <pub-id pub-id-type="doi">10.1007/BF00315284</pub-id>, PMID: <pub-id pub-id-type="pmid">8436160</pub-id></citation></ref>
<ref id="ref33"><label>33.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Adams</surname><given-names>JF</given-names></name></person-group>. <article-title>Biological half-life of vitamin B12 in plasma</article-title>. <source>Nature</source>. (<year>1963</year>) <volume>198</volume>:<fpage>200</fpage>. doi: <pub-id pub-id-type="doi">10.1038/198200a0</pub-id>, PMID: <pub-id pub-id-type="pmid">14010994</pub-id></citation></ref>
</ref-list>
</back>
</article>