CD and UC can be differentiated by their location and depth of involvement in the bowel wall. UC involves diffuse inflammation of the colonic mucosa and mostly affects the rectum (proctitis), but it may extend into the sigmoid (proctosigmoiditis), beyond the sigmoid (distal UC), or include the entire colon up to the cecum (pancolitis). CD results in transmural ulceration of any portion of the gastrointestinal tract (GI) most often affecting the terminal ileum and colon.⁴

Both diseases are classified by extent (mild, moderate, or severe) and location. CD also is classified by phenotype- inflammatory, stricturing, or penetrating. Women living with CD, generally have a milder disease course than men.^1,4

Besides the GI tract, both CD and UC have several extra-intestinal manifestations. While in most patients, the disorders can be distinguished, in at least 10% of patients, the features are so similar that it is not possible to initially differentiate between the two disorders.⁴

The exact cause of IBD has not yet been determined. Both disorders do have a genetic predisposition, however, environmental factors causing dysbiosis have been reported to be one of the leading causes of IBD.⁶

The gut microbiome of patients with IBD differs from that of healthy individuals. Among others, in patients with IBD with both exacerbation and remission, the presence of Clostridiaceae or adherence-invasive strains of Escherischia coli is found more often than in the general population. Furthermore, patients living with IBD show a reduction in the number of bacterial species with anti-inflammatory properties (eg Faecalibacterium prausnitzii).⁶

Neither CD nor UC is curable, and they both carry enormous morbidity. Finally, both increase the risk of colorectal cancer and in women, the risk of cervical cancer.^4,5

Symptoms of IBD include:⁴

• Diarrhoea may be associated with blood or mucus. Diarrhoea may also occur at night and faecal incontinence is not uncommon
• Some patients with UC may present with constipation when the disease is localised to the rectum
• Abdominal pain, tenesmus, and severe urgency are also common presentations
• CD can present with right lower quadrant pain and UC may present with left lower quadrant pain
• Nausea and vomiting are more common in CD.

During the physical examination, the following symptoms may be noted:⁴

• Tachycardia, anxiety, fever, and dehydration are common
• Depending on the anaemia, pallor may be noted
• Toxic megacolon may present with severe pain, fever, abdominal distension, chills, and lethargy
• In CD, one may note anal fistulas, abscesses, or even rectal prolapse
• Occult blood on a digital rectal exam is common.

The disease and its associated symptoms have a profound impact on the quality of life of women (QoL). Understanding the effects of gender on IBD allows personalised care and improves women's QoL, stresses Truta.^2,3

How does IBD impact women’s QoL?

Endometriosis is more frequent in women with than those without IBD, which may affect fertility. Women living with IBD also have an increased risk for negative body image, depression, anxiety, cervical dysplasia, and osteoporosis.^2,5

GI symptoms, surgery, and medications negatively affect body image and women often shy away from having sex. Body image perception and sexual dysfunction have an impact on both their physiological and psychological well-being and may require referral for cognitive behavioural therapy. It is extremely important that clinicians take these factors into consideration when consulting a female patient living with IBD, according to Goetgebuer et al.^3,5

Women living with IBD have higher rates of anxiety – especially those with CD. Rates of depression are similar between patients with UC and CD.⁵

Although fertility rates are similar in women living with IBD compared to the general population, many patients who had ileal pouch-anal anastomosis (IPAA) surgery, have decreased fertility rates and will require reproductive assistance.⁵

Women living with IBD have an increased risk of spontaneous preterm birth and giving birth to small-for-gestation-age infants. However, it is not a risk factor for congenital anomalies. Disease activity during pregnancy has been associated with preterm birth, low birth weight, miscarriage, and stillbirth. In general, IBD medications except for methotrexate.⁵

Women with IBD are at increased risk of cervical intraepithelial neoplasia (CIN) 2+ (defined as a combination of CIN2, CIN3, and cervical cancer lesions). These results underline the importance of human papillomavirus vaccination and adherence to cervical cancer screening guidelines in IBD women, regardless of exposure to immunosuppressants.³

The current European Crohn’s and Colitis Organisation guideline recommends an intensified screening approach in immunocompromised IBD women, and American guidelines recommend intensified screening only in IBD women using immunosuppressive medication.³

Lastly, an estimated 145%-42% of patients living with IBD have osteoporosis. The pathogenesis of bone loss in patients living with IBD is multifactorial. Long-term corticosteroid use, calcium and vitamin D deficiencies, malnutrition, and the systemic effects of chronic inflammation are thought to play a role. An additional risk factor for women with IBD is the loss of oestrogen as they approach menopause. It is vital to assess the bone density in patients who are administered steroids. Osteoporosis has significant morbidity in these patients. If steroid use for more than three months is expected, then calcium supplements and bisphosphonates should be introduced.^4,5

How is IBD treated and do probiotics have a role?

The goal of treatment is to induce remission for either UC or CD. Treatment of IBD is divided into the management of mild, moderate, and severe disease.⁴

UC treatment depends greatly on the extent of the disease and the presence of extraintestinal manifestations. For those with mild to moderate disease limited to the rectum, aminosalicylate agents like mesalamine are the mainstays.⁴

For those patients with moderate disease who are refractory to mescaline, oral glucocorticoids or immunomodulators such as TNF-alpha monoclonal antibodies (infliximab) may be an option.⁴

Up to 25% of all UC patients will require total colectomy for the uncontrolled disease. Proctocolectomy IPAA is the procedure of choice for elective cases. Flare-ups are usually managed with corticosteroid therapy. For those who have more than >1 flare-ups a year, the use of anti-TNF agents or other immunosuppressive is recommended.⁴

CD treatment depends on the portion of the GI tract involved, the degree of fistulising or stricturing, and any extra-intestinal complications. Treatment of mild ileocecal disease is usually begun with mesalamine, which can be further augmented with the use of oral budesonide, a steroid with significant first-pass metabolisation to limit systemic side effects.⁴

For more extensive disease, systemic steroid therapy with prednisone is necessary. The goal is to wean these steroids within six weeks. In those patients who cannot wean, an immunomodulating agent like 6-mercaptopurine, azathioprine, or low-dose methotrexate is added.⁴

In those patients with moderate to severe disease, anti-tumour necrosis factor therapy should be initiated. Before initiating biologic therapy, patients must complete a purified protein derivative test to assess for latent tuberculosis. Surgical treatment may be necessary for those with severe fistulising disease including diverting ostomy.⁴

Due to side effects associated with the long-term use of some medications to treat IBD, it has been reported that between 40% and 50% of patients living with IBD seek treatment with alternative therapies such as probiotics, which may mediate the inhibition of nuclear factor kappa B (NF kappa B).^6,7,8

In both IBDs, but particularly CD, increased activation of NF kappa B may be involved in the regulation of the inflammatory response. Inhibition of NF kappa B activation exerts an anti-inflammatory effect in IBD.⁸

The Food and Agriculture Organization of the United Nations and the World Health Organization defines probiotics as ‘live microorganisms, which when administered in adequate amounts, confer a health benefit on the host’.⁹

Scientific evidence backs the efficacy of probiotics in the treatment of traveller’s diarrhoea, HIV-associated diarrhoea, difficile colitis relapses, antibiotic-associated diarrhoea, irritable bowel syndrome, abdominal pain and bloating, UC and necrotising enterocolitis. It should be noted that the efficacy of probiotics is strain specific.^7,9

Probiotics work by inhibiting the overgrowth of potentially pathogenic bacteria to modify the composition in the bowel. The core benefit of probiotics is supporting a healthy immune system.^7,9

To evaluate the efficacy and safety of probiotics in the management plan of patients living with IBD, Jia et al conducted a meta-analysis, which included 10 studies.⁷

In summary, they found that the use of some types of probiotics could prevent the induction of inflammatory reactions in patients with IBD and could be considered as an alternative for patients with IBD.⁷

According to Akutko and Stawarski, several probiotic strains have been studied and may have significant benefits for patients living with UC. For example, Lactobacillus rhamnosus as monotherapy or together with mesalazine in patients with UC significantly prolonged clinical remission during one-year follow-up compared to the group treated with anti-inflammatory mesalazine alone.⁶

Furthermore, studies have shown that the use of probiotics as an alternative therapy may be particularly useful in treating patients with mesalamine intolerance. The authors do caution that probiotics should not be used in patients living with severe UC.⁶

Several studies have evaluated the efficacy of different probiotic strains both in inducing and maintaining remission, as well as in the prevention of exacerbations after surgery in patients living with CD. The use of probiotics has not been shown to be associated with a clinically significant benefit for patients with CD either in single studies or in a meta-analysis.⁶

References

1. American College of Gastroenterology. Common GI Problems in Women. [Internet]. Available from: https://gi.org/topics/common-gi-problems-in-women/
2. Truta B. The impact of inflammatory bowel disease on women's lives. Current Opinion in Gastroenterology, 2021.
3. Goetgebuer RL, et al, on behalf of the Dutch Initiative on Crohn and Colitis [ICC], Increased Risk of High-grade Cervical Neoplasia in Women with Inflammatory Bowel Disease: A Case-controlled Cohort Study, Journal of Crohn's and Colitis, 2021.
4. McDowell C, Farooq U, Haseeb M. Inflammatory Bowel Disease. [Updated 2023 Apr 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470312/
5. Veerisetty S, Eschete SO,  Uhlhorn A-P, De Felice KM. Women's Health in Inflammatory Bowel Disease. The American Journal of the Medical Sciences, 2018.
6. Akutko K, Stawarski A. Probiotics, Prebiotics and Synbiotics in Inflammatory Bowel Diseases. J Clin Med, 2021.
7. Jia K, Tong X, Wang R, Song X. The clinical effects of probiotics for inflammatory bowel disease: A meta-analysis. Medicine (Baltimore), 2018.
8. Schreiber S, Nikolaus S, Hampe J. Activation of nuclear factor kappa B inflammatory bowel disease. Gut,1998.
9. Hill C, Guarner F, Reid G, et al.The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol, 2014.